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Epidemiology, diagnosis and treatment of systemic Candida infection in surgical patients under intensive care
Abstract
The incidence of systemic Candida infections in patients requiring intensive care has increased substantially in recent years as a result of a combination of factors. More patients with severe underlying disease or immunosuppression from anti-neoplastic or anti-rejection chemotherapy and at risk from fungal infection are now admitted to the ICU. Improvements in supportive medical and surgical care have led to many patients who would previously have died as a result of trauma or disease surviving to receive intensive care. Moreover, some therapeutic interventions used in the ICU, most notably broad-spectrum antibiotics and intravascular catheters, are also associated with increased risks of candidiasis. Systemic Candida infections are associated with a high morbidity and mortality, but remain difficult to diagnose and ICU staff need to be acutely aware of this often insidious pathogen. A number of studies have identified risk factors for systemic Candida infection which may be used to identify those at highest risk. Such patients may be potential candidates for early, presumptive therapy. Here we review the epidemiology, pathogenesis, morbidity and mortality of systemic Candida infections in the ICU setting, and examine predisposing risk factors. Antifungal treatment, including the use of amphotericin B, flucytosine and fluconazole, and the roles of early presumptive therapy and prophylaxis, is also reviewed.
... 9 Fluconazole prophylaxis can reduce the incidence of Candida infection and colonization in selected critically ill patients, in both the medical and the surgical ICU settings. 2,7,17,28,29 The present study observed a complete response to IV fluconazole prophylaxis in 66% of patients. Studies have reported that early treatment with fluconazole has a favorable effect on the clinical course of high-risk patients and late antifungal treatment is associated with a poor prognosis. ...
... It has been suggested that early therapy be initiated in high-risk patients due to the high mortality, prevalence of invasive candidiasis, and poor reliability of available diagnostic methods. 29,[33][34][35] The present study shows that empiric antifungal treatment is common in the ICU setting in Spain and Germany. While an expert panel of the Infectious Disease Society of America no longer favors first-line fluconazole treatment in patients with moderately severe to severe illness or patients who have had recent azole exposure, 34 European recommendations, which were valid at study initiation, focused on the use of fluconazole. ...
... While an expert panel of the Infectious Disease Society of America no longer favors first-line fluconazole treatment in patients with moderately severe to severe illness or patients who have had recent azole exposure, 34 European recommendations, which were valid at study initiation, focused on the use of fluconazole. 29 The British Society for Antimicrobial Chemotherapy Working Party has recommended empiric therapy for surgical and ICU patients thought to have deep candidiasis but for whom microbiologic, histological, or serologic confirmation cannot be obtained. 35 This is also addressed in the most recent guidelines of the European Society of Clinical Microbiology and Infectious Diseases, which in addition downgraded fluconazole recommendation in non-neutropenic patients from AI to CIII. ...
... MIC testing of itraconazole was performed as per the procedure in the CLSI guidelines M27-A2, [9][10][11][12][13][14][15][16][17][18][19][20] using RPMI-1640 broth, an inoculum of 0.5-2.5X10 3 colony-forming units (cfu)/mL, incubation at 35°C, and MIC endpoint criteria of prominent inhibition of growth. 10 A serial dilution of the drug solution was made adding 100 µl of free bicarbonate RPMI-1640 into the first well (each lane of a 96-well plate), followed by a reduction in concentration (16.0000 to 0.0313 µg/mL). ...
... Patients at risk of systemic fungal infections (including candidiasis), such as those with a serious underlying disease, immunosuppression caused by cytotoxic/anti-rejection chemotherapy, corticosteroid therapy, and long-term antibiotic therapy, are on the increase. 11 Furthermore, fungal infections are recognised as a serious concern amongst the elderly population, as age is a risk factor because of its effect on mortality rates. 12,13 Presence of Candida colonisation on the skin surface and mucosa is a potential source of systemic infection, and the hands of medical personnel have been evidenced to play an important role in nosocomial infections with transmission from healthcare workers to patients in hospitals. ...
Background: There is an increasing incidence of life-threatening systemic mycoses, specifically fulminant infections by the Candida species in hospitalised patients and in those who are immunocompromised. Management of the limited number of antifungal drugs currently available requires the identification of infections containing drug-resistant isolates. Objectives: The aim of this study was to identify the non-albicans Candida species as azole-resistant fungi, isolated from sputum and bronchoalveolar lavage specimens of hospitalised cases. Methods: The subjects included hospital-acquired infection (HAI) cases, with a primary diagnosis using a direct microscopic examination, performed for the detection of probable fungi. The molecular tests of PCR-restriction fragment length polymorphism (RFLP) and real-time PCR were performed to confirm the identity and molecular typing of the Candida isolates. Antifungal susceptibility testing (AFST), by the Clinical and Laboratory Standards Institute (CLSI) broth microdilution (BMD) minimum inhibitory concentration (MIC) (M27-A2) method, was performed on the hospital-isolated Candida species. Results: During 24 months, from August 2014 to September 2016, a total of 198 samples were obtained from cases with proven HAI. The results of experimental studies on the specimens showed 93 (47%) positive cases for a fungal or bacterial infection, of which 54 (58%) had a fungal infection. It was hypothesised that all of the isolated organisms were causative agents of the HAI. Conclusions: The results showed that the medium CHROMagar™ Candida is an accessible and easy-to-use method for the identification of infection, but not as accurate and reliable as PCR-RFLP and real-time PCR methods. Results also showed decreasing susceptibility to azoles (itraconazole in this study) of the Candida species.
... 11 Fungal culture results are available in two to three days at the earliest, and blood and deep tissue sample cultures from infections with focal lesions are frequently negative. 12,13 Direct microscopy and histopathological examinations are rapid, but they do not always allow identification of the infecting agent to the species level. 11,13 In contrast, the latest generation of monoclonal antibody based, enzymelinked immunosorbent assays for circulating aspergillus and candida antigens are specific but lack sensitivity. ...
... 12,13 Direct microscopy and histopathological examinations are rapid, but they do not always allow identification of the infecting agent to the species level. 11,13 In contrast, the latest generation of monoclonal antibody based, enzymelinked immunosorbent assays for circulating aspergillus and candida antigens are specific but lack sensitivity. 11 Thus, rapid diagnostic methods that are both sensitive and specific are needed. ...
... substantial cause of lower genital infections in women, especially in developing countries where it caused significant loss of work hours and significant financial burden on the already weak economy. An estimated two-thirds of women will suffer at least one episode of VVC in their lives and 40-50% may experience multiple episodes (Vincent et al., 1998;Consolaro et al., 2004;García et al., 2005;Nyirjesy et al., 2005). The majority of cases of VVC are caused by Candida albicans and has become one of the pathogens most frequently isolated from the blood of postoperative and immunocompromised patients during the last decade (Komshian et al., 1989;Wahyuningsih et al., 2000). ...
... The majority of cases of VVC are caused by Candida albicans and has become one of the pathogens most frequently isolated from the blood of postoperative and immunocompromised patients during the last decade (Komshian et al., 1989;Wahyuningsih et al., 2000). Candida organisms probably access the vagina via migration from the rectum across theVC in their lives and 40-50% may experience multiple episodes (Vincent et al., 1998;Consolaro et al., 2004;García et al., 2005;Nyirjesy et al., 2005). The majority of cases of VVC are caused by Candida albicans and has become one of the pathogens most frequently isolated from the blood of postoperative and immunocompromised patients during the last decade (Komshian et al., 1989;Wahyuningsih et al., 2000). ...
Vulvovaginal candidiasis (VVC) is the most common genital infections that are seen every day in clinics. This infection is due to excessive growth of Candida that are normally present in the vagina in small numbers. Diagnosis of VVC is routinely done by direct microscopy of Pap smear samples and searching for the Candida in the Pap smear glass slides. This manual method is subjective, time consuming, labour-intensive and tedious. This study presents a computer-aided diagnostic (CAD) method to improve human diagnosis of VVC. The proposed CAD method reduces the diagnostic time and also can be worked as a second objective opinion for pathologists. Our main objective is detection and extraction of mycelium and conidium of Candida fungus from microscopic images of Pap smear samples. In this regard, the proposed method is composed of three main phases, namely preprocessing, segmentation, feature extraction and classification. At the first phase, bottom-hat filtering is used for elimination of the cervical cells and separating the background. Then decorrelation stretching and colour K-means clustering are used for Candida segmentation. Finally the extracted features used by a decision tree classifier to detect Candida from other parts of smear. The proposed method was evaluated on 200 Pap smear images and showed specificity of 99.83% and 99.62% and sensitivity of 92.18% and 94.53% for detection of mycelium and conidium, respectively.
... Le risque de développer une septicémie à Candida augmente avec la durée de la pose du cathéter (R.J. WILLIAMS et al., 1971). HENDERSON et al.,1996) ; (J.L. VINCENT et al., 1998) Le risque infectieux (risque de passage de l'état saprophyte à l'état pathogène) est étroitement relié au taux de portage (aspect quantitatif du saprophytisme). Il est démontré que chez les patients agranulocytaires des services d'hématooncologie, un saprophytisme candidosique digestif quantitativement important est prédictif d'un risque élevé de candidose systémique. ...
... 1-B-1--2) Les principales espèces de Candida isolées au cours du SIDA C. albicans est responsable de la majorité des candidoses associées au SIDA. VINCENT et al., 1998). L'amélioration du contrôle des chocs septiques et la réduction de la mortalité due aux bactéries gram négatif ont augmenté la probabilité d'une surinfection fongique. ...
... [4] Direct microscopy and Histopathological results are faster alternatives, although species identification is more challenging with these approaches. [16,17] Only three patients (33.33 %), in our study got positive microbial infection findings, i.e., two patients had a bacterial infection while only one patient had a fungal infection. That is why mortality in this study was related to underlying diseases rather than bacterial or fungal infection, as in AIFR. ...
... The candidiasis associated with IL-17 inhibitors is rarely systematic and mainly causes topical infection, among which oral candidiasis is prominent (Okada et al. 2016). However, the severity of candidiasis depends on the patient's underlying conditions, which might increase the severity of the infection (Vincent et al. 1998). The severity of the condition and whether the patient is pregnant often influence the initial therapy option. ...
The application of interleukin-17 (IL-17) inhibitors, including secukinumab, ixekizumab, brodalu-mab, and bimekizumab, are associated with elevated risk of candidiasis. These medications interfere with the IL-17 pathway, which is essential for maintaining mucosal barriers and coordinating the immune response against Candida species. The observational data and clinical trials demonstrate the increased incidence of candidiasis in individuals treated with IL-17 inhibitors. Brodalumab and bimekizumab pose a greater risk than secukinumab in eliciting candidiasis, whereas the data regarding ixekizumab are equivocal. Higher doses and prolonged treatment duration of IL-17 inhibitors increase the risk of candidiasis by compromising the immune response against Candida species. Prior to prescribing IL-17 inhibitors, healthcare professionals should comprehensively evaluate patients' medical histories and assess their risk factors. Patients should be educated on the signs and symptoms of candidiasis to facilitate early detection and intervention. Future research should focus on identifying the risk factors associated with candidiasis in patients receiving IL-17 inhibitors. Prospective studies and long-term surveillance are required to explore the impact of specific inhibitors on the incidence and severity of candidiasis and to evaluate the effectiveness of combination therapies, such as concurrent use of IL-17 inhibitors and prophylactic antifungal agents.
... High rates of morbidity and mortality are associated with invasive Candida infections. The rate of mortality from candidemia is about 30%, while directly attributable mortality is between 19 and 24% (40,41). Treating these infections requires antifungals that are expensive, and this is considered a burden in our country. ...
Background: Invasive fungal infections have presented a challenge in treatment.
In the past, it was known that the frontrunner in such infections is Candida
albicans with little emphasis placed on non-albicans Candida species (NAC).
Studies worldwide have shown a rise in fungal infections attributed to non-albicans
Candida species. The aim of this study is to describe the epidemiology of NAC
infections along with an overview of resistance in Lebanese hospitals.
Methods: This is a two-year observational multi-central descriptive study.
Between September 2016 and May of 2018, a total of 1000 isolates were collected
from 10 dierent hospitals distributed all over the country. For the culture,
Sabouraud Dextrose Agar was used. Antifungal Susceptibility was evaluated by
determining the Minimum Inhibitory Concentration (MIC) in broth (microdilution)
of the dierent antifungal treatments.
Results: Out of the 1000 collected isolates, Candida glabrata, being the most
isolated species (40.8%), followed by Candida tropicalis: 231(23.1%), Candida
parapsilosis: 103(10.3%), and otherNACspecies at lower percentage.Most of these
isolates (88.67%) were susceptible to posaconazole, 98.22% were susceptible to
micafungin, and 10% were susceptible to caspofungin.
Conclusion: The change of etiology of fungal infections involving a significant
increase in NAC cases is alarming due to the dierent antifungal susceptibility
patterns and the lack of local guidelines to guide the treatment. In this
context, proper identification of such organisms is of utmost importance.
... High rates of morbidity and mortality are associated with invasive Candida infections. The rate of mortality from candidemia is about 30%, while directly attributable mortality is between 19 and 24% (40,41). Treating these infections requires antifungals that are expensive, and this is considered a burden in our country. ...
Background
Invasive fungal infections have presented a challenge in treatment. In the past, it was known that the frontrunner in such infections is Candida albicans with little emphasis placed on non-albicans Candida species (NAC). Studies worldwide have shown a rise in fungal infections attributed to non-albicans Candida species. The aim of this study is to describe the epidemiology of NAC infections along with an overview of resistance in Lebanese hospitals.
Methods
This is a two-year observational multi-central descriptive study. Between September 2016 and May of 2018, a total of 1000 isolates were collected from 10 different hospitals distributed all over the country. For the culture, Sabouraud Dextrose Agar was used. Antifungal Susceptibility was evaluated by determining the Minimum Inhibitory Concentration (MIC) in broth (microdilution) of the different antifungal treatments.
Results
Out of the 1000 collected isolates, Candida glabrata, being the most isolated species (40.8%), followed by Candida tropicalis: 231(23.1%), Candida parapsilosis: 103(10.3%), and other NAC species at lower percentage. Most of these isolates (88.67%) were susceptible to posaconazole, 98.22% were susceptible to micafungin, and 10% were susceptible to caspofungin.
Conclusion
The change of etiology of fungal infections involving a significant increase in NAC cases is alarming due to the different antifungal susceptibility patterns and the lack of local guidelines to guide the treatment. In this context, proper identification of such organisms is of utmost importance. The data presented here can help in establishing guidelines for the treatment of candida infections to decrease morbidity and mortality. Future surveillance data are needed.
... Infections with E. coli can be the cause of diseases such as diarrhea, urinary tract infections, respiratory illness and pneumonia, septicemia, meningitis, and other infections [63,64]. Last, but not least, Candida albicans is an opportunistic fungal pathogen responsible for superficial mucosal infections and life-threatening systemic candidiasis [23,65,66]. All three genera are important etiological agents of implant-associated infections and orthopedic infections. ...
Hydroxyapatite (Ca10(PO4)6(OH)2, HAp), due to its high biocompatibility, is widely used as biomaterial. Doping with various ions of hydroxyapatite is performed to acquire properties as close as possible to the biological apatite present in bones and teeth. In this research the results of a study performed on thin films of hydroxyapatite co-doped with nitrogen and bromine (NBrHAp) are presented for the first time. The NBrHAp suspension was obtained by performing the adapted co-precipitation method using cetyltrimethylammonium bromide (CTAB). The thin layers of NBrHAp were obtained by spin-coating. The stability of the NBrHAp suspension was examined by ultrasound measurements. The thin layers obtained by the spin-coating method were examined by scanning electron microscopy (SEM), optical microscopy (OM), and metallographic microscopy (MM). The presence of nitrogen and bromine were highlighted by energy-dispersive X-ray spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS) studies. Fourier transform infrared spectroscopy (FTIR) was used to highlight the chemical status of nitrogen and bromine. In addition, the powder obtained from the NBrHAp suspension was analyzed by XRD. Moreover, the in vitro antimicrobial activity of the NBrHAp suspensions and coatings was investigated using the reference microbial strains Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, and Candida albicans ATCC 10231. The results highlighted the successful obtainment of N and Br co-doped hydroxyapatite suspension for the first time by an adapted co-precipitation method. The obtained suspension was used to produce pure NBrHAp composite thin films with superior morphological properties. The NBrHAp suspensions and coatings exhibited in vitro antimicrobial activity against bacterial and fungal strains and revealed their good antimicrobial activity.
... The changing epidemiology of Candida infections, with a rise of non-Candida albicans spp., is seen worldwide [3,50,51]. Infections include candidemia, intra-abdominal infections (IAI), catheter-associated infections, and urinary tract infections (UTI) [52][53][54]. Candidemia is perhaps the most common form of invasive candidiasis (IC) in ICU patients as confirmed by a Swiss study [55]. Candida species normally colonizing mucosal membranes in healthy individuals can predispose even these immunocompetent persons to invasive disease in lieu of changes in the microbiome due to antibiotic therapy, burns, diabetes, etc. ...
Purpose of the Review
Candida is a common commensal of the human skin and gastrointestinal tract causing infections in immunocompromised hosts. However, Candida has a variety of virulence factors and fitness attribute which make it capable of infecting even persons with otherwise intact immune system, especially those in critical care settings and with underlying co-morbidities. In this review, we describe the mechanisms behind the pathogenesis and diagnosis of Candida infections in such hosts.
Recent Findings
Both noninvasive and invasive infections can be seen especially in critically ill, hospitalized patients. The gold standard for diagnosis, despite low sensitivity, is blood and sterile body fluid culture. Combining clinical scores, fungal biomarkers, and nucleic acid amplification–based tests is necessary to guide early antifungal therapy.
Summary
Understanding of the pathogenesis of infections in critically ill non-neutropenic individuals can help in identifying potential diagnostic and therapeutic targets. Future studies in specific patient groups can help in stratifying patients needing antifungals.
... Yoğun bakım ünitesinde yatış süresi ile kandida infeksiyonu gelişim riski arasında doğru orantı mevcuttur. Yapılan çalışmalarda infeksiyonun çoğu olguda yatışın 7. ile 21. günleri arasında geliştiği bildirilmiştir [23,24] . Çalışmamızda olgu grubunun yatış süresi 183.9 ± 147.4 gün, kontrol grubunun yatış süresi 95.8 ± 86.5 olarak bulundu. ...
Introduction: An important part of hospital-acquired infections is fungal infections. The most isolated species in fungal infections are Candida species. Fungal infections are the 4th most common hospital-acquired infection type in the USA. The aim of this study was to determine the risk factors of candidemia, type distribution of Candida and antifungal susceptibility in adult patients.
Materials and Methods: In this case-control study, data obtained between January 2016 and January 2017 were evaluated retrospectively. Demographic characteristics, clinical risk factors, microbiological information, antifungal therapy and clinical outcome were obtained from the clinical records of the patients. Candida isolates were identified by using the YST ID card (bioMerieux, France) in the fully automated VITEK 2 Compact® system.
Results: A total of 61 patients (who were in an intensive care unit of a tertiary hospital) were included into our study. Thirty-three patients with candidemia were included in the case group and the remaining 30 (non candidemia) patients were included in the control group. Thirty-four (55.7%) of the patients were females and 27 (44.3%) were males. Hospitalization duration was 183.9 ± 147.4 in the case group while hospitalization duration was 95.8 ± 86.5 in the control group. The rate of death in the case group was 74.2% and this rate was 16.6% in the control group. Risk factors for candidemia included Total Parenteral Nutrition (OR= 12.117; 95% CI= 2.094-45.998; p< 0.001), age (OR= 1.058; 95% CI= 1.007-1.112; p< 0.001), and hospitalization duration (OR= 1.009; 95% CI= 1.001-1.017; p< 0.001). Among the candidemia agents, Candida parapsilosis (n= 15, 48.4%) was found the most dominant species. This was followed by Candida albicans (n= 10, 32.3%), Candida glabrata (n= 3, 9.7%), Candida kefyr (n= 2, 4.1%) and Candida tropicalis (n= 1, 3.2%).
Conclusion: Candidemia remains a major health problem in our country. Identification of risk factors of candidiasis together with antifungal sensitivity will lead to better management of preventive and therapeutic measures.
... Keywords: chronic generalized periodontitis, candida-associated periodontitis, species identification of fungi, composition of microflora of periodontal pockets, degree of dissemination of periodontal pockets, fungi of the genus Candida [29][30][31][32][33][34] ческого здравоохранения ставится не часто, что сказывается на результатах лечения [19][20][21][22][23][24]. ...
Subject. Yeast-like fungi of the genus Candida as opportunistic microorganisms found on the oral mucosa in more than a half of the human population. However, there is conflicting evidence about the frequency of Candida detection in periodontal pockets. It has been proved that the fungi of the genus Candida are identified in the content of the gingival furrow and the periodontal pockets in 10% - 90.5% of cases in different geographical regions. As a result of the interaction of the pathogenic periodontal microflora and yeast-like fungi of the genus Candida a burdened underlying disease is usually identified, though the clinical importance of microbial associations in its course is not taken into account. In this regard, the diagnosis of candida-associated periodontitis is not correctly established that leads to poor treatment results. Since different Candida species have inequal sensitivity to the antimycotic and antiseptic drugs used, it is important to investigate the microbial landscape and the Candida fungi contamination of the periodontal pockets to improve the effectiveness of treatment of the CGP. The aim is to study the microbial landscape of the periodontal pockets during the exacerbation of the CGP and to determine the incidence of candida-associated periodontitis.. Material and methods. The fungi species were identified with a set of morphological, biochemical and microbial culture methods. To confirm the diagnosis, culture studies were conducted, microscopic examination of print smears, as well as genoidentification of fungi in the material from the periodontal pocket using a polymerase chain reaction. Results. It was established that Candida-associated periodontitis occurs in 41.79% of cases. Species composition is mainly represented by Candida albicans and Candida Krusei. Conclusions. The degree of contamination of periodontal pockets with the fungi of the Candida genus is associated with the degree of severity of periodontitis. Low and medium levels of contamination are associated with chronic generalized periodontitis of mild degree, medium and high degrees of contamination are associated with the CGP of medium severity, high degree of contamination corresponds to severe forms of the CGP.
... Invasive candidiasis (IC) is a life-threatening disease caused by the genus Candida. The disease, which encompasses both candidemia (bloodstream yeast infection) and deep-seated candidiasis (infection of the tissues beneath mucosal surfaces) (Clancy and Nguyen, 2013), can occur following gastrointestinal surgery, which allows the fungus to penetrate the mucosa (Vincent et al., 2014), while neutropenia, caused by chemotherapy or by immunosuppression of solid-organ or hematological stem cell transplant patients, impairs immune system recognition, and clearance of Candida cells leading to disseminated infections (Safdar and Armstrong, 2011). An estimated 400,000 cases of Candida bloodstream infection occur globally each year (Brown et al., 2012), making up ∼3% of all nosocomial infections in Europe, and ∼12% in the United States (Schmiedel and Zimmerli, 2016). ...
The human commensal yeast Candida is the fourth most common cause of hospital-acquired bloodstream infections, with Candida albicans accounting for the majority of the >400,000 life-threatening infections annually. Diagnosis of invasive candidiasis (IC), a disease encompassing candidemia (blood-borne yeast infection) and deep-seated organ infections, is a major challenge since clinical manifestations of the disease are indistinguishable from viral, bacterial and other fungal diseases, and diagnostic tests for biomarkers in the bloodstream such as PCR, ELISA, and pan-fungal β-D-glucan lack either standardization, sensitivity, or specificity. Blood culture remains the gold standard for diagnosis, but test sensitivity is poor and turn-around time slow. Furthermore, cultures can only be obtained when the yeast resides in the bloodstream, with samples recovered from hematogenous infections often yielding negative results. Consequently, there is a pressing need for a diagnostic test that allows the identification of metastatic foci in deep-seated Candida infections, without the need for invasive biopsy. Here, we report the development of a highly specific mouse IgG3 monoclonal antibody (MC3) that binds to a putative β-1,2-mannan epitope present in high molecular weight mannoproteins and phospholipomannans on the surface of yeast and hyphal morphotypes of C. albicans, and its use as a [64Cu]NODAGA-labeled tracer for whole-body pre-clinical imaging of deep-seated C. albicans infections using antibody-guided positron emission tomography and magnetic resonance imaging (immunoPET/MRI). When used in a mouse intravenous (i.v.) challenge model that faithfully mimics disseminated C. albicans infections in humans, the [64Cu]NODAGA-MC3 tracer accurately detects infections of the kidney, the principal site of blood-borne candidiasis in this model. Using a strain of the emerging human pathogen Candida auris that reacts with MC3 in vitro, but which is non-infective in i.v. challenged mice, we demonstrate the accuracy of the tracer in diagnosing invasive infections in vivo. This pre-clinical study demonstrates the principle of using antibody-guided molecular imaging for detection of deep organ infections in IC, without the need for invasive tissue biopsy.
... One challenge in this study is that we cannot be sure that all fungal isolates detected were clinically relevant, as invasive candidiasis is a difficult diagnosis to arrive at with certainty [13][14][15]. Although yeast commonly are isolated in gastrointestinal perforations, they may be non-pathologic. ...
Background:
Fungi frequently are isolated in intra-abdominal infections (IAI). The Study to Optimize Peritoneal Infection Therapy (STOP-IT) recently suggested short-course treatment for patients with IAI. It remains unclear whether the presence of fungi in IAI affects the optimal duration of anti-microbial therapy. We hypothesized that a shorter treatment course in IAI with fungal organisms would be associated with a higher rate of treatment failure.
Methods:
Patients enrolled in the STOP-IT trial were stratified according to the presence or absence of a fungal isolate. They were analyzed as a subgroup based on original randomization to either the control group or an experimental group that received a four-day course of anti-microbial therapy and by comparison with those without a fungal component to their infection. Descriptive comparisons were performed using a χ2, Fisher exact, or Kruskal-Wallis test as appropriate. The primary outcome was a composite of recurrent IAI, surgical site infection, and death.
Results:
A total of 411 patients in the study (79%) had available culture data, of which 58 (14%) had positive fungal cultures. The most common organisms were Candida albicans and C. glabrata. The treatment failure rate was equivalent in the experimental and control arms (29.6% vs. 22.6%; p = 0.54). Patients with fungal isolates were more likely to have malignant disease (25.9% vs. 9.6%; p = 0.0004) and coronary artery disease (22% vs. 12%; p = 0.04), but were otherwise similar to those without fungal isolates. Patients with fungal isolates had more hospital days (median 10 vs. 7; p < 0.0001) and more days to resumption of enteral intake (median 5 vs. 3; p = 0.0006), but there was no difference in the composite outcome.
Conclusions:
Patients with IAI involving fungal organisms randomized to a shorter course of anti-microbial therapy had no difference in the rate of treatment failure. These results suggest that the presence of fungi in IAI may not indicate independently the need for a longer course of anti-microbial therapy.
... Secondary fungal peritonitis results from a breach in the gastrointestinal tract with gross contamination of the peritoneum. Candida was considered originally to be an insignificant, transient contaminant, but is now recognized as a serious nosocomial pathogen in non-neutropenic critically ill patients in intensive care units [14]. Peritonitis owing to candida has been reported in patients undergoing peritoneal dialysis and after gastrointestinal surgery [15]. ...
Spontaneous bacterial peritonitis is one of the most common and severe complications of
liver cirrhosis. Gram negative enteric pathogens are isolated in %80 of cases. Spontaneous
fungal peritonitis is rarely seen in cirrhosis.
Case Report: A 62 years old woman was admitted to our clinic with complaints of fever, weakness,
abdominal distention and pain, decrement in urine output and pain and hyperemia on
her face. She has diabetes mellitus for 10 years and cryptogenic cirrhosis for 3 years. She
has been using piperacillin tazobactam on admission. Spontaneous fungal peritonitis due
to candida albicans was diagnosed and treated successfully by caspofungin in this case.
Conclusions: Spontaneous fungal peritonitis must be suspected in patients with cirrhosis especially who
has been using wide spectrum antibiotic for a long time.
... Vulvovaginal candidiasis (VVC) is a yeast infection in women and caused by abnormal growth of yeasts in the mucosa of the female genital tract. Approximately 75% of women suffer from VVC yeast infection at least once in their lives and 40-50% will experience a recurrence (Consolaro et al., 2004;García et al., 2005;Vincent et al., 1998). In most cases, Candida albicans is the main reason of VVC (Komshian, Uwaydah, Sobel, & Crane, 1989). ...
Vulvovaginal candidiasis (VVC) is a common gynecologic infection and it occurs when there is overgrowth of the yeast called Candida. VVC diagnosis is usually done by observing a Pap smear sample under a microscope and searching for the conidium and mycelium components of Candida. This manual method is time consuming, subjective and tedious. Any diagnosis tools that detect VVC, semi- or full-automatically, can be very helpful to pathologists. This article presents a computer aided diagnosis (CAD) software to improve human diagnosis of VVC from Pap smear samples. The proposed software is designed based on phenotypic and morphology features of the Candida in Pap smear sample images. This software provide a user-friendly interface which consists of a set of image processing tools and analytical results that helps to detect Candida and determine severity of illness. The software was evaluated on 200 Pap smear sample images and obtained specificity of 91.04% and sensitivity of 92.48% to detect VVC. As a result, the use of the proposed software reduces diagnostic time and can be employed as a second objective opinion for pathologists.
... Suspension was kept at 37°C for 2 to 3 h. Culture was done on the CHROMagar Candida medium so that the clinical isolates were identified by comparing the color of colonies and considering the color introduced in catalog of the manufacturing company (Vincent et al. 1998). The green colonies and the colonies which had chlamydospore in microscopic study on corn meal agar containing Tween 80 were called Candida albicans. ...
Among the vulvovaginal infections, the second prevalent infection is vulvovaginal candidiasis which is created due to abnormal growth of Candida species in genital system of the women. Equisetum arvense is regarded as an effective drug in treatment of wounds. Quercus has been also used for treatment of many diseases. This study investigated 152 patients suspicious of vulvovaginal candidiasis. Seventy-five isolates were identified from 152 isolates of Candida albicans, and 55 yeast isolates were identified as non-albicans (Candida krusei, Candida glabrata, and Candida tropicalis), and 22 yeast isolates were unidentified. In broth microdilution method, MIC50 was reported as 12.5 μl/ml in Candida albicans for Equisetum arvense and Quercus, and MFC was reported as 25 μl/ml for both plants. In this research, isolation of Candida albicans species is more than that of non-albicans species.
... Candida species is a member of the normal flora of gastrointestinal tract and skin. Candidemia commonly develops in immuncompromised patients in relation with colonization in the body sites, broad-spectrum antibiotic use, and impairment of physiological barriers in the gastrointestinal system [7,8]. Candidemia was reported as fourth most common cause of nosocomial bloodstream infections in the United States and from fourth to seventh cause in Europe [9,10]. ...
Fungi are a part of environmental life. The use of yeasts
dates back to Sumeria 7000 B.C for beer. Fungi essentially
produce beer, wine, citric acid, single cell protein, fodder yeast,
and baker’s yeast. Fungi had become objects of interest with a
growing awareness as a material for botanical investigation at
the beginning of 1900s. It had contributed to development of
Biology, and Botany in the first fifty years of the 20th century.
Fungi are suitable material for investigation, as they can be
cultured under controlled conditions within a short time and
remain stable for long-term investigations as well. Diversity of
physiological activity, eighty to ninety thousand species within
their versatility according to taxonomic prejudice, from singlecelled
forms and simple aggregates to branching filamentous
pattern, sexual and asexual reproduction, and fusion between
filaments had made them study subject for scientists. Progress
in mycological work contributed to Botany and increased the
interest in this area
... Clinical risk factors for acquisition of Candida infection include neutropenia or a neutrophil defect whether heritable or epigenetic, systemic antibiotic usage, central venous catheter, mucosal damage, and prolonged stay in the ICU even in the presence of surfeit neutrophils (3,4). Candida infection is remarkably high in non-trauma emergency surgical patients with a prolonged ICU stay, reaching a rate of 21.7/100 discharges, higher than other established high-risk populations (5,6). ...
Neutrophils are motile and responsive to tissue injury and infection. As neutrophils emigrate from the bloodstream and migrate toward a site of affliction, they encounter the tissue extracellular matrix (ECM) and thereby engage integrins. Our laboratory studies the neutrophilic response to the fungal pathogen Candida albicans either in the filamentous state of the microbe or to the purified pathogen-associated molecular pattern, β-glucan. We have gained an appreciation for the role of integrins in regulating the neutrophil anti-Candida response and how the presence or absence of ECM can drive experimental outcome. The β2 integrin CR3 (complement receptor 3; αMβ2; Mac-1; CD11b/CD18) plays an important role in fungal recognition by its ability to bind β-glucan at a unique lectin-like domain. The presence of ECM differentially regulates essential neutrophil anti-fungal functions, including chemotaxis, respiratory burst, homotypic aggregation, and the release of neutrophil extracellular traps (NETs). We have shown that NET release to C. albicans hyphae or immobilized β-glucan occurs rapidly and without the requirement for respiratory burst on ECM. This is in contrast to the more frequently reported mechanisms of NETosis to other pathogens without the context of ECM, which occur after a prolonged lag period and require respiratory burst. As expected for an ECM-dependent phenotype, NETosis and other neutrophil functions are dependent on specific integrins. The focus of this review is the role of ECM ligation by neutrophil integrins as it pertains to host defense functions with an emphasis on lessons we have learned studying the anti-Candida response of human neutrophils.
... Cutaneous candidiasis is found in armpits, hands, groins, buttocks, and under breasts. Among the Candida species, Candida albicans isolated from oral cavity and skin folds are generally responsible for fungal diseases [2,25,26]. Thus, it is necessary and important to evaluation and identify novel alternative herbo-metallic antimicrobial agents for the above causative pathogens for number of ailments including skin and superficial infections. ...
Background
Mineral based preparations are widely used for centuries as antimicrobial agents. However, the efficacy and the mode of action of mineral based preparations are uncertain due to the insufficient antimicrobial studies. Arogyawardhana Vati (AV) and Manikya Rasa (MR) are such two Rasashastra herbo-minerallic drugs commonly in India and other countries in South Asia. Despite of their well known traditional use of skin diseases, reported antimicrobial and mineralogical studies are limited. Therefore, in this study antimicrobial activities of the drugs and their organic, inorganic fractions were evaluated against Pseudomonas aeruginosa, Escherischia coli, Staphylococcus aureus, Methecilline Resistance Staphylococcus aureus - MRSA and Candida albicans. Methods
Antimicrobial activity of the drugs, their inorganic residues and organic extracts were determined using four assay techniques viz agar well diffusion, modified well diffusion, Miles and Misra viable cell counting and broth turbidity measurements. Mineralogical constituents of the drugs were determined using X-ray diffraction, while total cation constituents and water soluble cation constituents were determined using inductively coupled plasma-mass spectrometer and the atomic absorption spectrophotometer respectively. Thermogravimetric analysis was used to determine the weight percentages of organic and inorganic fraction of the drugs. Particle sizes of the drugs were determined using the particle size analyzer. ResultsAV and MR drugs showed antibacterial activity against both gram positive and gram negative bacterial species when analyzed separately. Inorganic residues of the drugs and organic extracts showed activity at least against two or more bacterial species tested. All tested components were inactive against C. albicans. Common mineral constituents of drugs are cinnabar, biotite and Fe-rich phases. Drugs were rich in essential elements such as Na, K, Ca, Mg and Fe and toxic elements such as Zn, Cu and As. However, the water soluble concentrations of the toxic elements were below the detection limits. Both drugs have significantly higher percentages of organic constituents and volatile minerals and particle sizes of drugs are in the nanometer range. ConclusionsAV and MR Rasashastra preparations could provide alternatives to synthetic antibiotics against human bacterial infections. Improved solubility and reduced particle sizes are influential physicochemical properties used to enhance the antimicrobial efficacy of the drugs. Therefore, traditional knowledge on the use of antimicrobial mineral sources could provide a novel path for the producing of effective antimicrobial drugs. However, further chemical and toxicological studies are urgently needed for a greater understanding of their toxicity to humans.
... Within the last two decades, the opportunistic fungus Candida albicans was the pith of cogent medical interest since it still engenders substantial morbidity with significant mortality rates especially in immunosuppressed patients as HIV positive persons, cancer patients and transplant recipients among others [1,2].Candidiasis infection vary from superficial mucosal local lesions to a disseminative disease [3].The polymorph C.albicans fungus grows either in a yeast phase or as filamentous phase (hyphae). These two types of morphology could be present in infected tissues, thus it's possibly overt that both types contribute to the pathogenesis of the microorganism [4,5].Candidaspp are the most common causative agent in fungal contagions [6],representing a range of invasive life-threatening to non-life-threatening mucocutaneous diseases. ...
Abstract: The prevalence of fungal infections has raised in recent years due to an increasing population of immunosuppressed patients, intensive immunosuppressive chemotherapy, increasing awareness of fungal infections, and the widespread use of broad-spectrum antibiotics .Therefore, in the last few years, the development of novel diagnostic methods has been regarded a critical issue. A multiplex PCR strategy allowed the identification of 8 clinically relevant yeasts of the Candida genus, namely C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, C. guilliermondii, C. lusitaniae and C. dubliniensis. This method is relied on the amplification of two fragments from the ITS1 and ITS2 regions by the combination of 2 yeast-specific and 8 species specific primers in a single PCR reaction. This novel method provides a clinical diagnostic procedure with direct applicability.In addition to, it allows specific differentiation of individual Candida species within polyfungal samples. Keywords:Candida, candidemia, diagnostic, identification, PCR, multiplex
... In addition, non-C. albicans have shown resistance to two new antifungal drugs (voriconazole and ravuconazole), but it seems that antibiofilm activity of amphotericin B lipid formulation and also echinocandins have existed [13]. Therefore the aim of the present study was to evaluate antifungal susceptibility testing of Candida spp. ...
Aims. Biofilms formed by Candida species which associated with drastically enhanced resistance against most antimicrobial agents.The aim of this study was to identify and determine the antifungal susceptibility pattern of Candida species isolated from endotracheal tubes from ICU patients. Methods. One hundred forty ICU patients with tracheal tubes who were intubated and mechanically ventilated were surveyed for endotracheal tube biofilms. Samples were processed for quantitative microbial culture. Yeast isolates were identified to the species level based on morphological characteristics and their identity was confirmed by PCRRFLP. Antifungal susceptibility testing was determined according to CLSI document (M27-A3). Results. Ninety-five strains of Candida were obtained from endotracheal tubes of which C. albicans (𝑛 = 34; 35.7%) was the most frequently isolated species followed by other species which included C. glabrata (𝑛 = 24; 25.2%), C. parapsilosis (𝑛 = 16; 16.8%), C. tropicalis (𝑛 = 12; 12.6%), and C. krusei (𝑛 = 9; 9.4%).The resulting MIC90 for all Candida specieswere in increasing order as follows: caspofungin (0.5 𝜇g/mL); amphotericin B (2 𝜇g/mL); voriconazole (8.8 𝜇g/mL); itraconazole (16 𝜇g/mL); and fluconazole (64 𝜇g/mL).
Conclusion. Candida species recovered from endotracheal tube are the most susceptible to caspofungin.
Invasive fungal infections (IFIs) impose an enormous clinical, social, and economic burden on humankind. For many IFIs, ≥ 30% of patients fail therapy with existing antifungal drugs, including the widely used azole class. We previously identified a collection of 13 approved medications that antagonize azole activity. While gain-of-function mutants resulting in antifungal resistance are often associated with reduced fitness and virulence, it is currently unknown how exposure to azole antagonistic drugs impact C. albicans physiology, fitness, or virulence. In this study, we examined how exposure to azole antagonists affected C. albicans phenotype and capacity to cause disease. We discovered that most of the azole antagonists had little impact on fungal growth, morphology, stress tolerance, or gene transcription. However, aripiprazole had a modest impact on C. albicans hyphal growth and increased cell wall chitin content. It also worsened the outcome of disseminated infections in mice at human equivalent concentrations. This effect was abrogated in immunosuppressed mice, indicating an additional impact of aripiprazole on host immunity. Collectively, these data provide proof-of-principle that unanticipated drug-fungus interactions have the potential to influence the incidence and outcomes of invasive fungal disease.
Importance
As natural inhabitants of the gastrointestinal and reproductive tracts, Candida sp. are routinely exposed to medications consumed by their human host. This study provides new insight into how drugs can modulate the physiology, fitness, and pathogenicity of Candida albicans - one of the most important human fungal pathogens. These results provide a proof of principle that co-administered medications consumed by at-risk patients may influence the initiation and/or outcome of life-threatening fungal disease.
Background:
Systemic candidiasis is caused by Candida invading the bloodstream. The efficacy and safety of echinocandins in monotherapy and combination therapy regimes have not been adequately compared in immunocompromised patients with Candidiasis, and thus this systematic review aims to do so.
Methods:
A protocol was prepared a priori. PubMed, Embase and Cochrane Library databases were searched systematically (from inception of each database to September 2022) to identify randomized controlled trials. Two reviewers performed screening, quality assessment of trials, and extracted data independently. Pairwise meta-analysis was performed using random-effects model to compare echinocandin monotherapy versus other antifungals. The primary outcomes of interest were treatment success and treatment-related adverse events.
Results:
547 records (PubMed=310, EMBASE=210 and Cochrane Library=27) were reviewed. Following our screening criteria, six trials involving 177 patients were included. Risk of bias of four included studies had some concerns due to lack of a pre-specified analysis plan. Meta-analysis shows that echinocandin monotherapy does not have significantly higher rates of "treatment success" compared to other classes of antifungals (RR 1.12, 95%CI 0.80-1.56). However, echinocandins appeared to be significantly safer than other forms of antifungal therapy (RR 0.79, 95%CI 0.73-0.86).
Conclusion:
Our findings have shown that echinocandin monotherapy (micafungin, caspofungin) given intravenously are just as effective as other antifungals (amphotericin B, itraconazole) in the treatment of systemic candidiasis in immunocompromised patients. There appears to be similar benefits when using echinocandins compared to amphotericin B which has also been used as a broad-spectrum antifungal, while avoiding the severe adverse effects that amphotericin B causes, such as nephrotoxicity.
Candida Spezies gehören als kommensale Organismen zur normalen menschlichen Mikroflora, können allerdings unter bestimmten Bedingungen Krankheitswert erlangen. Limitationen in der Behandlung durch immer mehr resistente Candida Spezies und die wachsende Zahl immunsupprimierter Patienten gelten als Hauptursachen für die steigende Häufigkeit invasiver Candidosen und systemischer Candidämien. Die 2009 entdeckte Spezies C. auris stellt durch ihre zahlreichen Resistenzen, das Potential zur Auslösung nosokomialer Ausbrüche in Krankenhäusern und die schnelle Verbreitung über mehrere Kontinente eine neue Herausforderung dar. Der Bedarf an neuen Antimykotika mit anderen Wirkmechanismen und neuen Zielstrukturen ist größer denn je. Die fungale Sphingolipid-Biosynthese wurde bereits mehrfach als potenzielles Ziel antimykotischer Therapie diskutiert, allerdings bezieht sich die meiste Forschung hierzu auf C. albicans]. In vorliegender Arbeit wurden die Auswirkungen der Inhibition der Sphingolipid Biosynthese durch Myriocin auf C. auris und sein Resistenzverhalten untersucht und mit denen auf andere Candida Spezies verglichen. Sowohl die Mikrodilution als auch die Plattentropftests zeigten, dass C. auris verglichen mit anderen Candida Spezies besonders sensitiv auf die Anwesenheit von Myriocin reagierte und stärker im Wachstum gehemmt wurde. Der Survival Assay ergab für alle drei Spezies ein Absenken der CFU durch Myriocin, die Abweichungen zwischen den Stämmen waren jedoch unwesentlich. Unterschiede konnten in Vitalität und Vermehrung der verschiedenen Spezies unter Myriocineinfluss festgestellt werden. Aus der Lebend/Tot-Färbung ging hervor, dass Myriocin bei allen Stämmen zum Absterben von Candida Zellen führte, C. albicans und C. glabrata allerdings signifikant niedrigere Überlebensraten im Vergleich zu den C. auris Isolaten aufwiesen. Im Gegensatz dazu konnte mithilfe der FITC-Mikroskopie gezeigt werden, dass Candida Zellen unter Zugabe von Myriocin weniger Tochterzellen ausbildeten, was auf eine erschwerte oder zumindest verlangsamte Zellvermehrung hindeutet. Dabei schien das Wachstum der C. auris Stämme durch Myriocin deutlich eingeschränkter zu sein als das von C. albicans und C. glabrata. Durch weitere Mikroskopie und die Kombination aus Lebend/Tot Färbung mittels PI und FITC Färbung, sollte die Verteilung der toten Zellen auf Mutter- und Tochterzellen evaluiert werden. Hier konnte ein Trend zu einem vermehrten Zellsterben der Tochterzellen, vor allem für C. auris, festgestellt werden. Abschließende E-Tests für Amphotericin B, Anidulafungin und Fluconazol ergaben eine signifikante Herabsetzung der MHK für alle C. auris Isolate durch Myriocin. Die hier vorgestellten Ergebnisse und die durch mehrere Studien festgestellten Differenzen in der Sphingolipidkomposition von C. auris verglichen mit anderen Candida Spezies geben Hinweis darauf, dass Sphingolipide für Vitalität, Zellteilung und vor allem für die Wirkung einiger Antimykotika auf C. auris eine besondere, wenn nicht übergestellte Bedeutung haben könnten. Zwar wurde die Sphingolipidsynthese bereits mehrfach als potenzieller Angriffspunkt für die antifungale Therapie diskutiert, allerdings lediglich am Beispiel anderer Candida Spezies. Der Sphingolipidstoffwechsel könnte somit ein vielversprechender Ansatz für die Behandlung des sonst so therapieresistenten und lebensbedrohlichen Pilzes C. auris sein.
Fungal fatty acid (FA) synthase and desaturase enzymes are essential for the growth and virulence of human fungal pathogens. These enzymes are structurally distinct from their mammalian counterparts, making them attractive targets for antifungal development. However, there has been little progress in identifying chemotypes that target fungal FA biosynthesis. To accomplish this, we applied a whole-cell-based method known as Target Abundance-based FItness Screening using Candida albicans. Strains with varying levels of FA synthase or desaturase expression were grown in competition to screen a custom small-molecule library. Hit compounds were defined as preferentially inhibiting the growth of the low target-expressing strains. Dose-response experiments confirmed that 16 hits (11 with an acyl hydrazide core) differentially inhibited the growth of strains with an altered desaturase expression, indicating a specific chemical-target interaction. Exogenous unsaturated FAs restored C. albicans growth in the presence of inhibitory concentrations of the most potent acyl hydrazides, further supporting the primary mechanism being inhibition of FA desaturase. A systematic analysis of the structure-activity relationship confirmed the acyl hydrazide core as essential for inhibitory activity. This collection demonstrated broad-spectrum activity against Candida auris and mucormycetes and retained the activity against azole-resistant candida isolates. Finally, a preliminary analysis of toxicity to mammalian cells identified potential lead compounds with desirable selectivities. Collectively, these results establish a scaffold that targets fungal FA biosynthesis with a potential for development into novel therapeutics.
Invasive and disseminated Candida infections have become a major source of morbidity and mortality in neutropenic and nonneutropenic surgical intensive care patients. The incidence of Candida has increased: it is now the fourth most often isolated pathogen in bloodstream infections. After extended intraabdominal surgery and especially in emergency intraabdominal infection the abdomen is the predominant focus for candida infection. Intraabdominal candidiasis (IAC) is the predominant type of invasive candidiasis after candidemia. IAC is associated with mortality rates around 25–60%. Some studies have demonstrated almost a double mortality rate (48% versus 28%) in critically ill surgical patients with nosocomial fungal peritonitis compared to those without fungal infection. The diagnosis of postoperative candida infections is difficult because clinical signs and laboratory findings are unspecific. The decisive factors for a favorable outcome of infected patients are early diagnosis, adequate source control, as well as a prompt and appropriate anti-infective therapy.
Urinary tract infection (UTI) is a significant cause of morbidity in children. Delayed treatment is associated with complications that may result in chronic kidney disease and, subsequently, end-stage kidney disease. Over the years, clinical practice guidelines have advanced to ensure the best global practices in treating the infection and preventing its progression to chronic kidney disease.
The established practice guidelines address five main questions: 1) which children should have their urine tested; 2) how the sample should be obtained; 3) which radiological tests are recommended after a diagnosis of UTI; 4) how the infection should be treated; 5) and how affected children should be followed up. There is a substantial overlap in the recommendations of the American Academy of Pediatrics (AAP) guidelines and the UK’s National Institute for Health and Clinical Excellence (NICE) guidelines. Subtle differences, however, exist between the two established guidelines. An evidence-based paradigm shift of some traditional concepts about UTI in children has contributed to the revision and update of these guidelines. Further research is needed to clarify the role of host and genetic factors in renal scarring, as well as the diagnostic criteria for UTI. This narrative review aims to discuss the current recommendations of these established practice guidelines with an emphasis on the diagnosis, radiological investigation, treatment, and follow-up of UTI in children.
Visually identifying pathogens favors the rapid diagnosis at point-of-care testing level. Here, we developed a microenvironment-sensitive aggregation-induced emission luminogen (AIEgen), namely IQ-Cm, for achieving fast discrimination of Gram-negative bacteria, Gram-positive bacteria and fungi by naked-eye. With a twisted donor-acceptor and multi-rotors structure, IQ-Cm shows twisted intramolecular charge transfer (TICT) and AIE properties with sensitive fluorescence color response to the microenvironment of pathogens. Driven by the intrinsic structural difference of pathogens, IQ-Cm with a cationic isoquinolinium moiety and a membrane-active coumarin unit as targeting and interacting groups selectively locates in different sites of three pathogens and gives three naked-eye discernable emission colors. Gram-negative bacteria are weak pink, Gram-positive bacteria are orange-red and fungi are bright yellow. Meanwhile, based on their distinctive fluorescence response, IQ-Cm can directly discriminate three pathogens at the cell level under a fluorescence microscope. Furthermore, we demonstrated the feasibility of IQ-Cm as a visual probe for fast diagnosis of urinary tract infections, timely monitoring of hospital-acquired infection process and fast detection of molds in the food field. This simple visualization strategy based on one single AIEgen provides a promising platform for rapid pathogen detection and point-of-care diagnosis.
Background:
The considerable increase in the incidence of Candida infection in recent times has prompted the use of numerous antifungal agents, which has resulted in the development of resistance towards various antifungal agents. With rising Candida infections, the need for design and development of novel antifungal agents is in great demand. However, new therapeutic approaches are very essential in preventing the mortality rate and improving the patient outcome in those suffering from Candida infections.
Objective:
The present review objective is to describe the burden, types of Candidiasis, mechanism of action of antifungal agents and its resistance and the current novel approaches used to combat candidiasis.
Methods:
We have collected and analyzed 135 different peer-reviewed literature studies pertinent to candidiasis. In this review, we have compiled the major findings from these studies.
Results and conclusion:
The review describes the concerns related to candidiasis, its current treatment strategy, resistance mechanisms and imminent ways to tackle the problem. The review explored that natural plant extracts and essential oils could act as sources of newer therapeutic agents, however, the focus was on novel strategies, such as combinational therapy, new antibodies, utilization of photodynamic therapy and adaptive transfer primed immune cells with emphasis on the development of effective vaccination.
Subject. The problem of complex treatment of candida-associated periodontitis is considered. The authors propose a two-component probiotic, which, due to antagonistic activity regarding periodontal pathogenic infection and fungi of the genus Candida, leads to the relief of the inflammatory process, positive dynamics and stabilization of immunological parameters. The aim ― to evaluate the dynamics of clinical and immunological parameters in the complex treatment of candida-associated periodontitis with an average degree of quantitative seeding of periodontal pockets using a two-component probiotic. Methodology. A clinical and laboratory examination of three groups (I, II, III) of patients with Candida-associated periodontitis with an average degree of quantitative contamination of periodontal pockets (> 3 <6 CFU / ml) was carried out. Patients I groups were prescribed the well-known complex treatment including an antimycotic drug, patients II groups included a two-component probiotic locally in the treatment complex, and patients III groups locally and per os. The state of the oral mucosa was assessed, PMA, PI, OHI - S were determined, and indicators of cellular and humoral immunity were examined. Results. The study made it possible to establish that the inclusion of a two-component probiotic in the complex of treatment of candida-associated periodontitis with an average degree of quantitative contamination of periodontal pockets with fungi of the genus Candida contributes to the relief of the inflammatory process, an increase in phagocytosis, the metabolic activity of neutrophils, the concentration of immunoglobulins A, lysozyme levels, and a decrease in the concentration of immunoglobulins. G, positive dynamics of other indicators of immunity and their stabilization. Conclusions. The inclusion of a two-component probiotic from two strains in the complex treatment of chronic hepatitis C associated with fungi of the genus Candida contributes to the rapid relief of the inflammatory process in periodontal tissues, positive dynamics and stabilization of cellular and humoral immunity parameters.
The increasing incidence and high mortality rates associated with invasive fungal infections (IFIs) impose an enormous clinical, social, and economic burden on humankind. In addition to microbiological resistance to existing antifungal drugs, the large number of unexplained treatment failures is a serious concern. Due to the extremely limited therapeutic options available, it is critical to identify and understand the various causes of treatment failure if patient outcomes are to improve. In this study, we examined one potential source of treatment failure: antagonistic drug interactions. Using a simple screen, we systematically identified currently approved medications that undermine the antifungal activity of three major antifungal drugs - fluconazole, caspofungin, and amphotericin B - upon four prevalent human fungal pathogens – Candida albicans , Candida glabrata , Candida parapsilosis , and Candida tropicalis . This revealed that a diverse collection of structurally and functionally distinct drugs exhibit antagonistic interactions with fluconazole. Several antagonistic agents selected for follow-up studies induce azole resistance through a mechanism that depends upon Tac1p/Pdr1p zinc-cluster transcription factors, which activate the expression of drug efflux pumps belonging to the ABC-type transporter family. Few antagonistic interactions were identified with caspofungin or amphotericin B, possibly reflecting their cell-surface mode of action that should not be affected by drug efflux mechanisms. Given that patients at greatest risk of IFIs usually receive a multitude of drugs to treat various underlying conditions, these studies suggest that chemically inducible azole-resistance may be much more common and important than previously realized.
We have previously reported that an erg11 mutation affecting ergosterol synthesis and a hem13 mutation in the heme synthesis pathway significantly sensitize the fission yeast Schizosaccahromyces pombe to hydroxyurea (HU) (1, 2). Here we show that treatment with the inhibitors of Erg11 and the heme biosynthesis phenocopies the two mutations in sensitizing wild type cells to HU. Importantly, HU synergistically interacts with the heme biosynthesis inhibitor sampangine and several Erg11 inhibitors, the antifungal azoles, in causing cell lethality. Since the synergistic drug interactions are also observed in the phylogenetically divergent Saccharomyces cerevisiae and the opportunistic fungal pathogen Candida albicans, the synergism is likely conserved in eukaryotes. Interestingly, our genetic data in S. pombe has also led to the discovery of a robust synergism between sampangine and the azoles in C. albicans . Thus, combinations of HU, sampangine, and the azoles can be further studied as a new method for the treatment of fungal infections.
In the study, some new 1,3,4-thiadiazole compounds were synthesized and we have reported identification of the structures by using UV-Vis, FT-IR, ¹H NMR, ¹³C NMR and Mass spectroscopic methods. Antimicrobial activities of the compounds against three microorganisms, namely, Candida albicans ATCC 26555, Staphylococcus aureus ATCC 9144, and Escherichia coli ATCC 25922 were investigated by using disk diffusion method. These thiadiazoles exhibited an antimicrobial activity against Staphylococcus aureus and Candida albicans. The experimental data was supported by the quantum chemical calculations. Density functional theory (DFT) calculations were carried out to obtain the ground state optimized geometries of the molecules using the B3LYP, M06 and PBE1PBE methods with 3–21 g, 4–31 g, 6–311++g(2d,2p), cc-pvtz and cc-pvqz basis sets in the different combinations. Frontier molecular orbitals (FMOs) energies, band gap energies and some chemical reactivity parameters were calculated by using the aforementioned methods and basis sets, and the results were also compared with the experimental UV-Vis data.
Patients admitted to intensive care units (ICUs) represent 8 to 15% of overall hospital population [1]. A frequent problem related to ICU stay is the relative high incidence of infections, rates of which are higher than 40% as reported in some prevalence studies [2, 3]. This percentage is 5–10 times higher when compared with the infections in patients admitted in the normal wards; furthermore, in some hospitals of United States, recurrence of infections in ICUs represents more than 20% of overall nosocomial infections [4].
Background:
Immunosuppressive therapy places pediatric patients at risk of developing life-threatening sinonasal infections. Diagnosis and treatment is challenging owing to nonspecific signs and symptoms. The aim of the study was to present our department's experience with the surgical management of acute rhinosinusitis in immunosuppressed children.
Methods:
The records of all children with a hematologic or oncologic disease who underwent endoscopic sinus surgery (ESS) for acute rhinosinusitis from January 2005 to May 2014 were reviewed. Data were retrospectively collected on demographics, clinical and imaging characteristics, microbiology, pathology, treatment and outcome.
Results:
Thirty-four immunosuppressed children underwent ESS for acute rhinosinusitis. Most patients had a fungal infection. Nineteen patients died at the end of follow-up; ten deaths were infection-related. Facial swelling was the only symptom that correlated with death of infection. Relapse of the underlying disease, bone marrow transplantation, and long duration of neutropenia correlated with infection-related mortality. Fungal infection, and specifically Aspergillus, correlated with death from infection.
Conclusions:
ESS is a safe and efficient procedure for diagnosing and treating immunosuppressed pediatric patients with acute rhinosinusitis. Early detection and aggressive medical and surgical treatment, with control of underlying risk factors, are crucial to improve outcome.
The incidence of invasive fungal infections has increased steadily, namely due to the increasing number of immunocompromised and critically ill patients. Candida spp. is by far the most frequent fungal pathogen isolated in critically ill patients, accounting for more than 85 % of fungal infections. Intensive care candidiasis represents 25 – 50 % of all invasive candidiasis. The incidence of candidemia, although rather variable from unit to unit, ranging from 2.8 to 22 per 10 000 patient days, is tenfold higher in the intensive care unit (ICU) than in the wards and Candida species are responsible for around 10 % of all ICU-acquired infections worldwide. In the recent Sepsis Occurrence in Acutely ill Patients (SOAP) study, Candida spp. accounted for 17 % of all cases of sepsis in the ICU and for 20 % of all ICU-acquired sepsis [1]. In the large, multicenter Extended Prevalence of Infection in the ICU (EPIC II) study, fungi were responsible for 20 % of all microbiologically documented infections and Candida spp. was the main fungal pathogen (17 %) [2]. However, previously uncommon or even new fungal pathogens are increasing in the ICU, namely Aspergillus spp. (mainly Aspergillus fumigatus), Zygomycetes (mainly Mucor and Rhizopus) and Fusarium. In recent years, several reports have described an increasing incidence of invasive pulmonary aspergillosis in critically ill patients admitted to the ICU, even in the absence of an apparent predisposing immunodeficiency, such as neutropenia or hematologic malignancy. Factors like the use of steroids, chronic obstructive pulmonary disease (COPD) and chronic liver failure seem to be associated with the development of invasive pulmonary aspergillosis in the ICU, whose incidence ranges from 0.3 % to as much as 5.8 % [3]–[5].
Candidemia and systemic candidiasis were considered rare diseases until the 1950s; in 1964, only 48 cases of disseminated candidiasis were described. Endemic mycosis such as coccid-iomycosis, blastomycosis and histoplasmosis, described in the early twentieth century, remained a medical curiosity for a long time.
Fungal infections are a significant problem and represent a major cause of morbidity and mortality in a variety of patients. Improvements in supportive care and widespread use of antimicrobial agents have resulted in an expanding population of at-risk patients. This trend concerns not only severely compromised hosts such as transplant recipients, neutropenic and HIV-positive patients but also non-compromised patients on surgical and medical intensive care units (ICUs), burns and neonatal units with specific risk factors for infection.
In 1990 National Nosocomial Infection Surveillance (NISS) Program data heightened the awareness of nosocomial fungal infections in the U.S. During the 1980s nosocomial fungal infection rates doubled andCandidaspecies(Candidasp.) emerged as the sixth most common nosocomial pathogen. Increases in fungal infection rates occurred regardless of hospital type or size and were primarily due to one genus,Candidasp, which caused nearly 80% of all nosocomial fungal infections (1,2).
It has been shown in the last decade that the incidence of nosocomial fungal infections is increasing both in the USA (1) and in European hospitals (2,3). In the ICU setting Candida species are the most common cause of invasive fungal infections. The increase in nosocomial invasive candidosis parallels the advance made in the medical and surgical supportive care towards survival of critically ill patients, which would previously have died of severe illness. One of the most important risk factors for development of invasive fungal infections in these debilitated patients is the enormous increase in appropriate or in-appropriate use of broad spectrum antibiotics. Carefully considered presumptive treatment of infectious diseases in the ICU prior to establishment of a diagnosis is a common and proper practice of medicine. However ill-considered use of antibiotics can lead to a spiraling empiricism of antibiotic therapy incurring unnecessary risk of side effects and ultimately fungal infections (4). Their modulation of the bacterial flora induces an overgrowth of gastrointestinal Candida colonization which is a major first step in the development of invasive candidosis. It is an important task for the ICU physician to prevent development of invasive fungal infections because of its high attributable mortality. Appropriate use of broad spectrum antibiotics, strict hygienic measures and preemptive treatment with antimycotics in a certain subset of ICU patients with identified risk factors should prove essential to decrease the number of patients with invasive fungal disease. Neutropenic patients and transplant recipients is a distinct group with regard
Candida is an opportunistic yeast normally found in the oral cavity and gastrointestinal tract. Its ability to multiply and to invade the bloodstream and deep tissues is increasing. This has produced new clinical patterns of systemic disease whose expression is dependent on the immune status of the host. Thus, presence of Candida is intimately linked to the effects of chemotherapy and radiation therapy for cancer, hematological malignancies, human immunodeficiency virus (HIV) infection, malnutrition, corticosteroid therapy, and broad-spectrum antibiotics.
The presence of fever in patients in the surgical intensive care unit (SICU) demands prompt attention because infection, often heralded by an elevation in core body temperature, is the leading cause of death in this patient population (1). Fever is defined as “a state of elevated core temperature,” and is present when the oral temperature is higher than 99°F (>37.3°C) in the early morning or higher than 100°F (>37.8°C) at any time during the day. This frame of reference is obviously of limited value when applied to seriously ill patients in the SICU, some of whom may exhibit an absent or blunt response to infection and others who are not candidates for oral temperature measurements. Most authorities consider the thermistor of a pulmonary artery catheter to be the most accurate device for measuring core temperature. However, when pulmonary artery catheters are not in place, most believe that electronic probes, placed in the rectum or external auditory canal, are acceptable alternatives. Measurements from the axilla are unreliable and should not be used (2).
Die Bedeutung einer adäquaten intensivmedizinischen Antibiotikatherapie in Verbindung mit sinnvollen und konsequent durchgeführten hygienischen Maßnahmen geht aus folgenden Fakten klar hervor:
Patienten auf Intensivstationen haben im Krankenhaus das höchste Infektionsrisiko [13].
Multiorganversagen ist die Haupttodesursache von Intensivpatienten und wird überwiegend durch septische Komplikationen ausgelöst oder unterhalten [50].
In den USA erkranken jährlich etwa 400.000 Patienten an einer Sepsis, etwa die Hälfte davon (200.000) erleiden einen septischen Schock, der bei ca. 50% der Patienten tödlich verläuft [63].
10-30% der Mortalität auf Intensivstationen werden nosokomialen Pneumonien zugeschrieben [71].
Objective. The aims of this study were to evaluate the use of intravenous antifungal agents and to compare the strategies and the drugs used with those recommended in the guidelines of our hospital. Method. 1) We established recommendations issued from the data of the published guidelines and the experience of the local specialists. We proposed a decisional guide with a simplified classification. 2) A prospective study was conducted from January to June 2001 including all adults and children treated with intravenous antifungal agents. Collection of prescribed antifungal therapy and clinical data allowed a classification and judgement of the strategy (i.e. disease prevention, empirical and curative therapy). Results. One hundred twenty-one patients were treated during this period. All the patients were at high risk of developing invasive fungal infections because of their underlying disease. The antifungal drugs prescribed were amphotericin B (AMB) in 26% of the cases, liposomal amphotericin B in 14% and fluconazole (FCZ) in 54%. Therapy was modified in 29%, in general because of nephrotoxicity or unfavorable course. The treatments were prescribed in 21% of cases for disease prevention (including 88% of FCZ), in 36% of cases as empirical treatment with similar use of AMB and FCZ and finally in 42% the antifungal drugs were prescribed as curative treatment using FCZ in 65% of candidosis and AMB in all filamentous fungal infections. Conclusion. This study shows that the choice of the drugs was well adapted to the recommendations. The drug generally prescribed in hematology for disease prevention, empirical or curative treatment was AMB. In the absence of prolonged neutropenia and in the absence of criteria of candidosis severity, FCZ remained the drug of choice.
Introduction. Although there has been an improved management of Invasive Candidiasis in the last decade, controversial issues still remain, especially in the diagnostic and therapeutic approaches. Objectives. We sought to identify the core clinical knowledge and to achieve high level agreement recommendations required to care for critically ill adult patients with Invasive Candidiasis. Methods. Prospective Spanish survey reaching consensus by the Delphi technique, anonymously conducted by electronic e-mail in a first term to 25 national multidisciplinary experts in invasive fungal infections from five national scientific societies, including Intensivists, Anesthesiologists, Microbiologists, Pharmacologists and Infectious Disease Specialists, responding to 47 questions prepared by a coordination group after a strict review of the literature in the last five years. The educational objectives spanned five categories, including epidemiology, diagnostic tools, prediction rules, and treatment and de-escalation approaches. The level of agreement achieved among the panel experts in each item should exceed 75% to be selected. In a second term, after extracting recommendations from the selected items, a face to face meeting was performed where more than 80 specialists in a second round were invited to validate the preselected recommendations. Measurements and Main Results. In the first term, 20 recommendations were preselected (Epidemiology 4, Scores 3, Diagnostic tools 4, Treatment 6 and De-escalation approaches 3). After the second round, the following 12 were validated: Epidemiology: Think about Candidiasis in your ICU and do not forget that non-albicans species also exist. Diagnostic tools: Blood cultures should be performed under suspicion every 2-3 days and, if positive, every 3 days until obtaining the first negative result. Obtain sterile fluid and tissue, if possible (direct examination of the sample is important). Use nonculture based methods of microbiological tools, whenever possible. Determination of antifungal susceptibility is mandatory. Scores: As screening tool, use the Candida Score and determine multicolonization in high risk patients. Treatment: Start early. Choose Echinocandins. Withdraw the catheter. Fundoscopy is needed. De-escalation: Only applied when knowing susceptibility determinations and after 3 days of clinical stability. The higher rate of agreement was achieved in the optimization of microbiological tools and the withdrawal of the catheter, whereas the lower rate corresponded to de-escalation therapy and the use of scores. Conclusions. The management of invasive candidiasis in ICU patients requires the application of a broad range of knowledge and skills that our summarized in our recommendations. These recommendations may help to identify the potential patients, standardize their global management and improve their outcomes, based on the DELPHI methodology.
Superficial and systemic fungal infections are a major problem among severely immunocompromised patients who undergo bone marrow transplantation. We performed a double-blind, randomized, multicenter trial in which patients receiving bone marrow transplants were randomly assigned to receive placebo or fluconazole (400 mg daily). Fluconazole or placebo was administered prophylactically from the start of the conditioning regimen until the neutrophil count returned to 1000 per microliter, toxicity was suspected, or a systemic fungal infection was suspected or proved.
By the end of the treatment period, 67.2 percent of the 177 patients assigned to placebo had a positive fungal culture of specimens from any site, as compared with 29.6 percent of the 179 patients assigned to fluconazole. Among these, superficial infections were diagnosed in 33.3 percent of the patients receiving placebo and in 8.4 percent of the patients receiving fluconazole (P less than 0.001). Systemic fungal infections occurred in 28 patients who received placebo as compared with 5 who received fluconazole (15.8 percent vs. 2.8 percent, P less than 0.001). Fluconazole prevented infection with all strains of candida except Candida krusei. Fluconazole was well tolerated, although patients who received it had a higher mean increase in alanine aminotransferase levels than patients who received placebo. Although there was no significant difference in overall mortality between the groups, fewer deaths were ascribed to acute systemic fungal infections in the group receiving fluconazole than in the group receiving placebo (1 of 179 vs. 10 of 177, P less than 0.001).
Prophylactic administration of fluconazole to recipients of bone marrow transplants reduces the incidence of both systemic and superficial fungal infections.
The incidence of fungal infection, particularly with Candida species, has increased dramatically over the past decade [1]. Data from the National Nosocomial Infections Surveillance (NNIS) system show that between 1980 and 1989, the incidence of primary bloodstream infections attributable to Candida species increased by 487% in large teaching hospitals and by 219% in small hospitals ( < 200 beds) [2].
Deep Candida infections are increasing in incidence, especially in non-neutropenic, intensive care patients including neonates. The attributable mortality of candidaemia and candida peritonitis is 37-38% with a 57% overall mortality. The BSAC set up a working party to develop recommendations for management in the absence of controlled trials. These recommendations focus on the role of the microbiology laboratory, management strategies, the respective roles of amphotericin B, flucytosine and fluconazole and long-term maintenance therapy. The indications for initiation of therapy are given special consideration.
The application of methods of Candida albicans DNA fragment length polymorphism analysis to correlations with phenotype and to questions in the epidemiology of Candida is shown. Twenty-nine different DNA types, in two broad classes, have thus far been demonstrated in 91 isolates. One type,
IA2, was easily the most common (41% of isolates). A type is constant after multiple generations in vivo, as demonstrated
in a mouse model. Isolates from individual medical centers were polymorphic, and DNA types were widely distributed geographically.
Persons colonized with and/or having disease due to C. albicans at two or more body sites almost always had the same individual type. Sex partners studied had the same type in genital isolates.
There was neither tight concordance nor random association of DNA type with previously described phenotypic groups. Likewise,
some phenotypic characteristics were significantly associated with DNA type. Urogenital isolates were significantly associated
with DNA type IA2. Colonizing and invading isolates included many different and overlapping DNA types. A cluster of cases
in a hospital, previously reported to have been caused by a single organism (based on phenotypic studies), was shown to be
due to multiple types. Phenotype switching, associated with transition from colonization to invasion, is suggested in these
studies. The present series of studies demonstrates the application of DNA typing methods to classification and clinical problems.
Adherence of bacteria to intestinal epithelial cells may be the crucial initiating event for translocation and is normally prevented by both specific (secretory IgA) and nonspecific (mucus, bacterial antagonism, desquamation) mucosal defense mechanisms. The purpose of this study was to examine the effect of dexamethasone administration on mucosal immunity; specifically bacterial adherence and IgA. Twenty Fischer rats were randomly assigned to two groups of 10 animals each. Group I received 0.5 mL saline injection intraperitoneal (IP); and group II, 0.8 mg/150 g body weight dexamethasone IP per day for 2 consecutive days. The cecum, mesenteric lymph nodes, and bile were aseptically collected, and bacterial adherence, bacterial translocation, and IgA concentration were determined. Results indicate that, compared with saline-treated animals, dexamethasone-treated animals had a fall in IgA (54 +/- 24 versus 232 +/- 41 ng/mg protein), an increase in bacterial adherence (8.2 +/- 0.5 versus 3.4 +/- 0.6 cfu (log10)/g cecum), and an increased incidence of bacterial translocation to the mesenteric lymph nodes (60% versus 0%). These data suggest that glucocorticoids may promote bacterial translocation by impairment of mucosal IgA synthesis.
• The microbiology of infection acquired in the intensive care unit (ICU) was studied prospectively in 205 consecutive patients admitted to a surgical intensive care unit. A multiple organ failure (MOF) score was calculated for each admission. Susceptibility to ICU-acquired infection increased with increasing MOF scores. While Escherichia coli, Bacteroides fragilis, and enterococci were the most common isolates from infections present at the time of ICU admission, Staphylococcus epidermidis, Candida, and Pseudomonas dominated infections occurring in patients with high MOF scores. Mortality correlated highly with infection due to S epidermidis or Candida and only poorly with infection due to Pseudomonas or E coli; significant foci of invasive infection were frequently absent at autopsy. Quantitative cultures of proximal gastrointestinal fluid in 16 of these patients showed Candida, S epidermidis, and Pseudomonas to be the most common isolates, and all but one patient colonized with these organisms had invasive infection with the same organism. The proximal gastrointestinal tract appears to be an important occult reservoir of the predominant pathogens in MOF.
(Arch Surg 1988;123:309-315)
Objective: To evaluate the efficacy and safety of fluconazole for prevention of fungal infections. Design: A randomized, placebo-controlled, double-blind, multicenter trial. Patients: Adults (257) undergoing chemotherapy for acute leukemia. Intervention: Patients were randomly assigned to receive either fluconazole (400 mg orally once daily or 200 mg intravenously every 12 hours) or placebo. The study drug was started at initiation of chemotherapy and continued until recovery of neutrophil count, development of proven or suspected invasive fungal infection, or the occurrence of a drug-related toxicity
• Nosocomial candidemia has become an important infection not only because of an apparently increasing incidence but also because of its high fatality rate. We studied 28 risk factors through a matched case-control study that included 88 pairs of patients hospitalized between July 1983 and December 1986. The strongest single risk factor found in the univariate analysis was the number of prior antibiotics administered: the exposure odds ratio (OR) was 12.50 when patients who received three to five antibiotics were compared with those who received none to two antibiotics. A multiple logistic regression analysis using a conditional likelihood method was performed to evaluate several risk factors simultaneously. The final model selected by a stepwise procedure Included the following variables: number of antibiotics received prior to infection (OR, 1.73 per unit increase), isolation of Candida species from sites other than blood (OR, 10.37), prior hemodialysis (OR, 18.13), and prior use of a Hickman catheter (OR, 7.23). It remains to be shown in controlled clinical trials whether limiting the number of antibiotics or instituting prophylaxis and/or early treatment for high-risk patients will reduce the incidence of nosocomial candidemia.
(Arch Intern Med. 1989;149:2349-2353)
Background:
Candida is becoming an important nosocomial pathogen as the incidence of hospital-acquired candidemia is rising. Candida endophthalmitis is a good indicator of systemic candidiasis in hospitalized patients.
Methods:
Thirteen (17%) of 76 ophthalmologic consultations for Candida endophthalmitis in our institution had positive findings during a 12-month period. We studied these 13 patients with Candida endophthalmitis to evaluate their outcomes.
Results:
All 13 patients were admitted to a large tertiary care hospital, and 10 (77%) were in an intensive care unit. The overall mortality was 77% for all patients and 80% for the intensive care patients. This mortality was higher than the overall mortality for all patients in the surgical intensive care unit in our institution (17%), as well as the mortality for our patients with candidemia in the surgical intensive care unit (61%).
Conclusions:
The strikingly high mortality in our group of patients with Candida endophthalmitis reflects the fact that they are a seriously ill group with multiple risk factors for Candida infection. This information suggests that the presence of Candida endophthalmitis is a good indicator of high mortality in seriously ill patients in intensive care units.(Arch Intern Med. 1994;154:2093-2097)
• Between 1977 and 1984, estimates of hospital-acquired bloodstream infections caused by Candida species increased in the United States from 0.5 to 1.5 per 10000 admissions (National Nosocomial Infection Study data). We examined crude and attributable mortality rates and excess length of stay in 88 closely matched pairs of cases and controls with illnesses occurring between July 1983 and December 1986. The crude mortality rates for cases and controls were 57% and 19%, respectively; thus the attributable mortality rate was 38% with a 95% confidence interval of 26% to 49%. The risk ratio was 2.94 with a 95% confidence interval of 1.95 to 4.43. The median length of stay was 48 days for all cases and 40 days for all controls. An analysis of the length of stay for the 34 matched pairs that survived showed a median of 70 days for cases and 40 days for controls. Candida bloodstream infections represented 10% of all nosocomial bloodstream infections in the period studied at our University Hospital; they are associated with a significant medical and economic burden well above that expected of the underlying diseases alone.
(Arch Intern Med 1988;148:2642-2645)
Optimal chemoprophylaxis for fungal infection is not yet well defined. This study evaluates the respective roles of oral amphotericin B and fluconazole in granulocytopenic cancer patients. Fluconazole was better tolerated and had to be discontinued in only 1 of 30 patients compared with 5 of 29 patients receiving amphotericin B. The number of febrile episodes was similar in each group, but the median duration of prophylaxis prior to the first fever episode was longer in patients receiving fluconazole (8 days) than in those receiving amphotericin B (5 days). The number of patients requiring the initiation of intravenous amphotericin B was similar in each group. Documented fungal infections occurred in 4 patients receiving fluconazole and 6 receiving amphotericin B, including 2 patients in each group who developed fungaemia. No invasive candidiasis caused by Candida albicans was observed. Although the overall mortality was similar in each group, there was only one fungal death in the fluconazole group (due to aspergillosis) compared with 3 in the amphotericin B group (due to aspergillosis or trichosporosis).
DeepCandida infections are increasing in incidence, especially in non-neutropenic, intensive care patients including neonates. The attributable mortality of candidaemia andcandida peritonitis is 37–38% with a 57% overall mortality. The BSAC set up a working party to develop recommendations for management in the absence of controlled trials. These recommendations focus on the role of the microbiology laboratory, management strategies, the respective roles of amphotericin B, flucytosine and fluconazole and long-term maintenance therapy. The indications for initiation of therapy are given special consideration.
In the past decade there has been a dramatic increase in the incidence of life-threatening Candida infections in patients in intensive care units (ICUs). Once considered a minor pathogen, Candida is now among the most commonly cultured pathogens in the ICU. This phenomenon is in part attributable to greater numbers of immunocompromised patients being hospitalized and the more frequent use of surgery, instrumentation, and broadspectrum antibiotics. Serious Candida infections can present as generalized sepsis, as focal involvement of virtually any organ, or as part of the syndrome of multiple system organ failure. Once established, these infections can be difficult to detect until their late stages and consequently are responsible for significant morbidity and mortality in ICU patients. For treatment to be successful it must be instituted promptly and, on occasion, empirically. As a result, new diagnostic techniques, treatments, and prophylactic strategies to minimize the occurrence of Candida infections are the subjects of ongoing research. This article is intended to provide practitioners with an understanding of why serious Candida infections are increasing, as well as information on pathogenesis, diagnosis, treatment, and some measures that can be taken to prevent such infections in critically ill patients.
Nosocomial infection is a common complication of hospital admission affecting 5-10% of admissions in general hospitals. Although intensive care units (ICUs) make up only 5% of hospital beds, infections acquired in these units account for at least 20% of nosocomial infections. Rates of infection are two- to fivefold higher for ICU patients than for those admitted to general wards.
Objective.
—To determine the prevalence of intensive care unit (ICU)—acquired infections and the risk factors for these infections, identify the predominant infecting organisms, and evaluate the relationship between ICU-acquired infection and mortality.
In a four-month period, 371 isolates of Candida (C albicans, 68%; C tropicalis, 31%) were identified at Boston City Hospital. Sputum, urine, and wounds were the most frequent sources, in that order. Inocula replicating tests for susceptibility to eight antimicrobials showed that hamycin and amphotericin B were the most active; nystatin, kalafungin and endomycin ranked next; flucytosine (5-fluorocytosine) was slightly active and lomofungin and rifampin were inactive. Review of clinical records of 41 patients with apparent Candida infection revealed a high incidence of multiple chronic diseases and high fatality rates. Acquisition of Candida was associated with prolonged hospitalization and antibiotic therapy, candiduria with indwelling urinary catheters, and candidemia with intravenous catheters. There was only one case of systemic candidiasis. Specific therapy is rarely required for apparent Candida infection in hospitalized patients.
The successful management of invasive fungal infections continues to plague the clinician. They are
associated with an unacceptably high morbidity and mortality, with reliable diagnostics a major issue.
Although well described in the immunocompromised, especially haemato-oncology patients, there is no
doubt that these infections are on the rise in the critically ill, intensive care patient. This article aims to
examine and focus on the changing epidemiology, problems with diagnostics and the management of
such life threatening sepsis
Candida species are responsible for the large majority of fungal infections acquired in critically ill patients. Candida infections have become increasingly important. Infections mainly evolve from endogenous colonization facilitated by the use of broad-spectrum antibiotics. The intensity of Candida species colonization constitutes a strong predictor of subsequent infection. Hand carriage of Candida species is, however, highly prevalent in ICUs, and nosocomial transmission has been documented. Careful epidemiologic investigation coupled with intraspecies delineation of Candida strains are frequently necessary for a complete understanding of the infection process. New drugs available will offer better alternatives for earlier intervention strategies.
(C) Lippincott-Raven Publishers.
The results of surveillance cultures in 424 neutropenic patients with hematologic malignancies were analyzed to evaluate the relationship between colonization and infection by Candida species. Eighteen (32%) of 56 patients with multiple noncontiguous colonized sites developed proven (13 cases) or probable (five cases) systemic candidiasis, versus two patients with proven candidiasis (1.2%) of 170 with one colonized site (P < 0.00000001), and one patient with proven candidiasis (0.5%) of 198 without any evidence of Candida colonization (P < 0.00000001). Twenty-two patients with multiple colonized sites who developed a febrile episode resistant to antibiotics were treated with empiric amphotericin B. Nine of 11 given empiric amphotericin B within day 6 survived versus three of 11 receiving antifungal therapy after day 6 (P = 0.014). The above data seem to justify further prospective studies on Candida colonization as indication to early antifungal therapy in febrile neutropenic patients.
More than 25,000 primary bloodstream infections (BSIs) were identified by 124 National Nosocomial Infections Surveillance System hospitals performing hospital-wide surveillance during the 10-year period 1980–1989. These hospitals reported 6,729 hospital-months of data, during which time approximately 9 million patients were discharged. BSI rates by hospital stratum (based on bed size and teaching affiliation) and pathogen groups were calculated. In 1989, the overall BSI rates for small (<200 beds) nonteaching, large nonteaching, small (<500 beds) teaching, and large teaching hospitals were 1.3, 2.5, 3.8, and 6.5 BSIs per 1,000 discharges, respectively. Over the period 1980–1989, significant increases (p < 0.0001) were observed within each hospital stratum, in the overall BSI rate and the BSI rate due to each of the following pathogen groups: coagulase-negative staphylococci, Staphylococcus aureus, enterococci, and Candida species. In contrast, the BSI rate due to gram-negative bacilli remained stable over the decade, in all strata. Except for small nonteaching hospitals, the greatest increase in BSI rates was observed in coagulase-negative staphylococci (the percentage increase ranged between 424% and 754%), followed by Candida species (219–487%). In small nonteaching hospitals, the greatest increase was for S. aureus (283%), followed by enterococci (169%) and coagulase-negative staphylococci (161%). Our analysis documents the emergence over the last decade of coagulase-negative staphylococci as one of the most frequently occurring pathogens in BSI.
Subclinical intestinal ischemia-reperfusion injury (IRI) causes an increase in mucosal permeability and may represent an early event in the pathogenesis of necrotizing enterocolitis. The present study was undertaken to determine whether these changes are mediated by local or systemic factors. In 6-week-old weanling rats, the ileum was divided into two isolated loops with separate vascular supplies. The mesentery of the proximal loop was occluded for 30 minutes, following which the bowel was reperfused; permeability to 51Cr EDTA was then assessed in the distal loop 30 minutes after reperfusion. In control groups, the distal loop was subjected to 30-minute IRI ("positive" control) or 30-minute sham operation ("negative" control). Permeability in the distal loop was increased only with IRI to the distal bowel (15.4 +/- 3 counts/min/standard), and not with IRI to the proximal bowel (5.1 +/- 1) or with sham operation (8.5 +/- 2). To determine whether a mild "priming" injury might be necessary for systemic factors to have an effect, the distal loop was subjected to 2-minute IRI and the proximal to 30-minute IRI or sham. Permeability was not increased in the distal loop in either of these groups (5.7 +/- 1 and 7.8 +/- 2, respectively). Thirty-minute IRI in the proximal loop did not increase permeability in the distal loop, with or without a priming injury. Only direct IRI in the distal loop resulted in a significant increase in permeability. We conclude that the permeability changes in this model are mediated through local tissue effects, rather than by systemic factors.
Demographic information, risk factors, therapy, and outcome for all patients who had candidemia at Barnes Hospital, St. Louis,
between 1 September 1988 and 1 September 1989 were retrospectively reviewed. One hundred six candidemic patients were identified,
representing 0.5% of all medical and surgical discharges and 0.33% of total patient discharges. These percentages represent
a 20-fold increase in the incidence of candidemia at our hospital in comparison with that during 1976–1979. Candida albieans was the most frequently isolated species (63%), followed by Candida tropiealis (17%), Candida glabrata (13%), Candida parapsilosis (6.5%), and Candida krusei (0.9%). Overall mortality was 57%, and 14 (23%) of 60 deaths occurred within 48 hours of the detection of candidemia. Mortality
was associated with higher APACHE II scores (25 for nonsurvivors vs. 16 for survivors; P = .0001), the presence of a rapidly fatal underlying illness (P = .0009), and sustained positivity of blood cultures (P = .02). In cases of sustained candidemia, the isolation of non-albieans Candida species also correlated with increased mortality (8 of 8 vs. 10 of 21; P = .005). Thirty candidemic patients (28%) did not receive any antifungal therapy, and 19 (63%) of these untreated patients
died. Eleven untreated patients (37%) survived without sequelae. There has been a marked increase in the incidence of candidemia
in our institution that is associated with a high overall mortality. Candidemia lasting <24 hours was associated with a lower
mortality than was that of longer duration. Severity of illness and duration of candidemia should be used as stratifying factors
in prospective studies to determine optimum therapy.
To determine the distribution of pathogens causing nosocomial infections in United States hospitals, we analysed data from
the National Nosocomial Infections Surveillance (NNIS) System. From October 1986 to December 1990, amongst hospitals conducting
hospital-wide surveillance, the five most commonly reported pathogens were Escherichia coli (13·7%), Staphylococcus aureus (11·2%), enterococci (10·7%), Pseudomonas aeruginosa (10·1%), and coagulase-negative staphylococci (9·7%). The commonest pathogens reported by site included, bloodstream: coagulase-negative
staphylococci, S. aureus, enterococci, E. coli, and Candida spp.; lower respiratory tract infection: S. aureus. P. aeruginosa and Enterobacter spp.; surgical wound infection: S. aureus, enterococci and coagulase-negative staphylococci; and urinary tract infection: E. coli, enterococci, and P. aeruginosa. Among hospitals conducting intensive care unit (ICU) surveillance, the commonest pathogens were P. aeruginosa (12·4%), S. aureus (12·3%), coagulase-negative staphylococci (10·2%), Candida spp. (10·1%), Enterobacter spp. and enterococci (8·6% each). In the ICUs, the commonest pathogens found in the bloodstream were coagulase-negative staphylococci,
S. aureus, and enterococci; in lower respiratory tract infections P. aeruginosa, S. aureus, and enterococci; in surgical wound infections enterococci, coagulase-negative staphylococci, and Enterobacter spp. and in urinary tract infections Candida spp., E. coli, enterococci, P. aeruginosa, and Enterobacter spp. These data show that S. aureus, E. coli and P. aeruginosa remain important nosocomial pathogens, that coagulase-negative staphylococci, enterococci and C. albicans are pathogens of increasing importance, and that the distribution of pathogens differs by site and hospital location.
Five previous outbreaks of disseminated candidosis due to Candida albicans are reviewed and a new outbreak on a neonatal unit in Belfast presented. This involved four disseminated cases. The control and definition of outbreaks by morpho-, immunoblot- and DNA-typing is discussed. An outbreak of Torulopsis glabrata infection involving 23 patients is described. This was defined by DNA fingerprinting with the enzyme Xba. There were five deaths attributable either completely or in part to the yeast infection.
Adherence of bacteria to intestinal epithelial cells may be the crucial initiating event for translocation and is normally prevented by both specific (secretory IgA) and nonspecific (mucus, bacterial antagonism, desquamation) mucosal defense mechanisms. The purpose of this study was to examine the effect of dexamethasone administration on mucosal immunity; specifically bacterial adherence and IgA. Twenty Fischer rats were randomly assigned to two groups of 10 animals each. Group I received 0.5 mL saline injection intraperitoneally (IP); and group II, 0.8 mg/150 g body weight dexamethasone IP per day for 2 consecutive days. The cecum mesenteric lymph nodes, and bile were aseptically collected, and bacterial adherence, bacterial translocation, and IgA concentration were determined. Results indicate that, compared with saline-treated animals, dexamethasone-treated animals had a fall in IgA (54 +/- 24 versus 232 +/- 41 micrograms/mg protein), an increase in bacterial adherence (8.2 +/- 0.5 versus 3.4 +/- 0.6 cfu (log10)/g cecum), and an increased incidence of bacterial translocation to the mesenteric lymph nodes (60% versus 0%). These data suggest that glucocorticoids may promote bacterial translocation by impairment of mucosal IgA synthesis.
To study the efficacy of fluconazole against chronic disseminated candidiasis (hepatosplenic candidiasis) in patients with leukemia in whom amphotericin B treatment had failed.
Retrospective analysis of patients with chronic disseminated candidiasis treated with fluconazole on a compassionate investigational new drug protocol.
Multi-institutional.
Twenty consecutive patients received 100 to 400 mg of fluconazole per day for a median of 30 weeks. All had either failed to respond to treatment with more than 2 g of amphotericin B or had serious amphotericin B-related toxicities.
Fourteen of 16 evaluable patients (88%) responded. Responses were observed in seven of nine patients in whom adequate doses of amphotericin B had failed and in all seven patients who had amphotericin B-related toxicities. In 12 patients, cytotoxic chemotherapy was continued without flare of the infection. Fluconazole was well tolerated with rare side effects. Aspergillus superinfection developed in three patients and contributed to the death of two of them.
Fluconazole is a safe and effective agent with significant activity against chronic disseminated candidiasis.
To determine if fluconazole is effective treatment for hepatosplenic candidiasis that has not resolved with amphotericin B and flucytosine treatment.
Six patients (ages 3 to 44) with acute leukemia and hepatosplenic candidiasis who did not respond to prior antifungal therapy were treated with fluconazole.
All six patients had fever and three had nausea and vomiting; computed tomographic (CT) scan showed lucencies in the liver in six, lucencies in the spleen in five, and lucencies in the kidneys in three. Prior therapy with 1.6 to 4 g of amphotericin B in the five adults and 526 mg of amphotericin B in the child (with the addition of flucytosine in four) failed to improve clinical symptoms or lucencies in the liver, spleen, and kidneys seen on CT scan. Fluconazole was given at a dose of 200 to 400 mg daily (70 to 100 mg in the child) for 2 to 14 months. All patients had resolution of fever and other symptoms in 2 to 8 weeks. Improvement of the lesions noted on CT scan was seen in 4 to 8 weeks in all patients. Total resolution of lesions noted on CT scan occurred by 4 weeks in two patients, but took 4 to 5 months for three patients and 13 months for one patient. Three patients had relapse of their acute leukemia and two died, presumably cured of their candidiasis. Two patients underwent successful bone marrow transplantation without relapse of their candidiasis.
Fluconazole appears to be useful in the treatment of hepatosplenic candidiasis that has not resolved with amphotericin B and flucytosine therapy.
More than 25,000 primary bloodstream infections (BSIs) were identified by 124 National Nosocomial Infections Surveillance System hospitals performing hospital-wide surveillance during the 10-year period 1980-1989. These hospitals reported 6,729 hospital-months of data, during which time approximately 9 million patients were discharged. BSI rates by hospital stratum (based on bed size and teaching affiliation) and pathogen groups were calculated. In 1989, the overall BSI rates for small (less than 200 beds) nonteaching, large nonteaching, small (less than 500 beds) teaching, and large teaching hospitals were 1.3, 2.5, 3.8, and 6.5 BSIs per 1,000 discharges, respectively. Over the period 1980-1989, significant increases (p less than 0.0001) were observed within each hospital stratum, in the overall BSI rate and the BSI rate due to each of the following pathogen groups: coagulase-negative staphylococci, Staphylococcus aureus, enterococci, and Candida species. In contrast, the BSI rate due to gram-negative bacilli remained stable over the decade, in all strata. Except for small nonteaching hospitals, the greatest increase in BSI rates was observed in coagulase-negative staphylococci (the percentage increase ranged between 424% and 754%), followed by Candida species (219-487%). In small nonteaching hospitals, the greatest increase was for S. aureus (283%), followed by enterococci (169%) and coagulase-negative staphylococci (161%). Our analysis documents the emergence over the last decade of coagulase-negative staphylococci as one of the most frequently occurring pathogens in BSI.
To determine trends in the microbial etiology of nosocomial infections in the 1980s, surveillance data on the microbiology of documented nosocomial infection reported to the National Nosocomial Infections Surveillance System and from the University of Michigan Hospital were analyzed. Antimicrobial susceptibility data on selected pathogens from both sources were also reviewed. Overall, Escherichia coli decreased from 23% of infections in 1980 to 16% in 1986-1989, Klebsiella pneumoniae dropped from 7% to 5%, whereas coagulase negative staphylococci increased from 4% to 9% and Candida albicans increased from 2% to 5%. Staphylococcus aureus, Pseudomonas aeruginosa, Enterobacter species and enterococci had minor increases, but antimicrobial resistant strains for these pathogens as well as coagulase-negative staphylococci were seen more frequently. In contrast to the 1970s, major shifts in the etiology of nosocomial infection have occurred in the decade of the 1980s. Taken as a whole, the shifts are away from more easily treated pathogens toward more resistant pathogens with fewer options for therapy. These shifts underscore the continued need for prevention and control to accompany new developments in therapy.
To examine the longitudinal and cross-sectional patterns of yeast colonization in critically ill patients using genotypic characteristics defined by contour-clamped homogeneous electric field (CHEF) gel electrophoresis, 322 clinical isolates of Candida species were prospectively collected from 29 critically ill patients under routine surveillance over a 6-month period. All isolates, recovered from multiple anatomic sites and from the same sites on different days, were characterized by several identification methods (germ tube test), phenotyping (API system), and genotyping (electrophoretic karyotyping). Electrophoretic karyotype (EK) was determined using pulsed field electrophoresis with the CHEF technique. We used a karyotyping system for Candida albicans (EK code) that facilitated intraspecies delineation. C. albicans colonized 83% of the 29 patients. Candida sp. strains isolated from an individual patient had an identical EK pattern, even when isolated from different body sites, and remained the same over a prolonged period, up to 140 days. EK delineated not only the different Candida species, but also different strains of C. albicans. Strains of C. albicans isolated from different patients were distinguished using the EK pattern, but not API system. Minor variations in EK pattern could be demonstrated in a minority of strains recovered from four patients and were interpreted as chromosomal rearrangements between parent strains. Severe candidal infections, including eight episodes of fungemia, occurred in 11 of 29 patients (38%). All patients had been previously colonized with strains with identical EK patterns. Infection occurred a mean of 25 days after initial surveillance cultures grew yeast. No horizontal transmission could be demonstrated during the study period. In conclusion, EK is a reproducible, stable marker allowing inter-, as well as, intraspecies Candida strain delineation. EK strain delineation is a useful tool in candidal epidemiologic and pathogenic studies. Yeast colonization with the same strain preceded infection in critically ill patients.
The application of methods of Candida albicans DNA fragment length polymorphism analysis to correlations with phenotype and to questions in the epidemiology of Candida is shown. Twenty-nine different DNA types, in two broad classes, have thus far been demonstrated in 91 isolates. One type, IA2, was easily the most common (41% of isolates). A type is constant after multiple generations in vivo, as demonstrated in a mouse model. Isolates from individual medical centers were polymorphic, and DNA types were widely distributed geographically. Persons colonized with and/or having disease due to C. albicans at two or more body sites almost always had the same individual type. Sex partners studied had the same type in genital isolates. There was neither tight concordance nor random association of DNA type with previously described phenotypic groups. Likewise, some phenotypic characteristics were significantly associated with DNA type. Urogenital isolates were significantly associated with DNA type IA2. Colonizing and invading isolates included many different and overlapping DNA types. A cluster of cases in a hospital, previously reported to have been caused by a single organism (based on phenotypic studies), was shown to be due to multiple types. Phenotype switching, associated with transition from colonization to invasion, is suggested in these studies. The present series of studies demonstrates the application of DNA typing methods to classification and clinical problems.
THE evolution of fungi of the genus candida from infrequent pathogens to among the most common agents of nosocomial infection has been both dynamic and interesting. The story of their emergence began in the early 1960s with events remarkably similar to those (recently recounted in the Journal by Klein1) involving the transformation of coagulase-negative staphylococci from a harmless commensal to an invasive pathogen. The severity of the problem is illustrated by the data collected by the National Nosocomial Infections Surveillance System during the past decade. Jarvis and colleagues2 reported studying 344,610 nosocomial pathogens reported to the surveillance system between . . .
The present investigation was performed to study the kinetics of tissue distribution and deposition of Escherichia coli and endotoxin translocating from the intestine after thermal injury. Escherichia coli was grown in the presence of 14C glucose and both labeled bacteria and endotoxin prepared from the labeled bacteria were used as translocation probes. Escherichia coli (10(8) to 10(10) bacteria) and E. coli endotoxin (100 micrograms per animal) were gavaged into the stomach immediately before a 30% burn injury was inflicted in mice. Animals were killed 1, 4 and 24 hours after burn injury. Translocation occurred extensively within 1 hour after burn injury. Expressed as amount of radioactivity per gram of tissue, translocation was greatest in the mesenteric lymph node (MLN) followed by spleen, lung, and liver. Translocation of endotoxin was similar to translocation of intact bacteria, with the exception that less radioactivity could be found in the peritoneal cavity and more in the liver. Both intact E. coli and endotoxin translocated directly through the intact bowel wall. Killing of bacteria was greatest in the MLN and spleen, approximating 95% to more than 99% of translocating bacteria. Killing efficiency was lowest in the lungs. It is concluded that estimation of translocation by viable bacterial counts in tissues grossly underestimates the extent of translocation of bacteria and ignores the extent of translocation of endotoxin. Translocation of endotoxin may have biologic significance that is independent of and in addition to translocation of intact bacteria.