European Journal of Clinical Microbiology & Infectious Diseases

Published by Springer Nature

Online ISSN: 1435-4373


Print ISSN: 0934-9723


Overview of the mass spectra of C. difficile PCR-ribotypes 001 (A), 027 (B) and 126/078 (C) in comparison to the mass spectrum of Clostridium orbiscindens (D). Each peak represents the mass of an intact protein detected in the analyses while the height of the peak depends on the amount of proteins measured. Specific masses are indicated by stars. RT ribotype, Int. intensity, m/z mass-to-charge-relation
Number of tested C. difficile isolates (double measurement) and distribution of the detected masses
Recognition of Clostridium difficile PCR-ribotypes 001, 027 and 126/078 using an extended MALDI-TOF MS system
  • Article
  • Full-text available

April 2011


133 Reads






During the last decade, Clostridium difficile infection (CDI) increased markedly inside as well as outside of hospitals. In association with the occurrence of new hypervirulent C. difficile strains, CDI became more important. Until now typing of C. difficile strains has been enabled by PCR-ribotyping. However, this method is restricted to specialized laboratories combined with high maintenance cost. Therefore, we tested MALDI-TOF mass spectrometry for typing of C. difficile to provide a fast method for surveillance of CDI. Using a standard set of 25 different C. difficile PCR ribotypes a database was made by different mass spectra recorded in the SARAMIS software (AnagnosTec, Zossen, Germany). The database was validated with 355 C. difficile strains belonging to 29 different PCR ribotypes collected prospectively from all submitted feces samples in 2009. The most frequent PCR ribotypes were type 001 (70%), 027 (4.8%) and 078/126 (4.7%). All three types were recognized by MALDI-TOF MS. We conclude that an extended MALDI-TOF system was capable to recognize specific markers for ribotypes 001, 027 and 078/126 allowing an effective identification of these strains.

Table 1 Ribotype distribution of toxin-producing strains of Clostrid- ium difficile among 307 patients in Hong Kong
Table 2 Demographic characteristics of 29 patients with culture isolation of Clostridium difficile ribotype 002 in Hong Kong
Workup for Clostridium difficile PCR ribotype 002 in a healthcare region in Hong Kong (1 January 2009 to 31 December 2009). a169 strains from 145 patients were found to have cytotoxin production by cell culture cytotoxicity neutralization assay (CCCNA) from both stool filtrates and C. difficile isolates. Another 176 strains from 162 patients had negative cytotoxin production in stool filtrates but positive toxin production in the culture supernatant of C. difficile isolates
Dendrogram of Clostridium difficile PCR ribotype 002 among 29 patients. Note: the strain number among 29 patients’ isolates and the standard strains of different PCR ribotypes from the Netherlands are listed
Trend of isolation of toxigenic Clostridium difficile in a healthcare region in Hong Kong. Note: toxigenic Clostridium difficile isolation per 1,000 admissions in: period 1 (2004–2008): 0.53 vs. period 2 (2009): 0.95 (p-value < 0.001); Percentage of patients positive for toxigenic Clostridium difficile: period 1 (2004–2008): 4.17% vs. period 2 (2009): 6.28% (p-value < 0.001)
Clostridium difficile isolates with increased sporulation: Emergence of PCR ribotype 002 in Hong Kong

April 2011


193 Reads

We identified a predominant clone of Clostridium difficile PCR ribotype 002, which was associated with an increased sporulation frequency. In 2009, 3,528 stool samples from 2,440 patients were tested for toxigenic C. difficile in a healthcare region in Hong Kong. A total of 345 toxigenic strains from 307 (13.3%) patients were found. Ribotype 002 was the predominant ribotype, which constituted 35 samples from 29 (9.4%) patients. The mean sporulation frequency of ribotype 002 was 20.2%, which was significantly higher than that of the 56 randomly selected ribotypes other than 002 as concurrent controls (3.7%, p < 0.001). Patients carrying toxigenic ribotype 002 were more frequently admitted from an elderly home (p = 0.01) and received more β-lactam antibiotics in the preceding 3 months compared with the controls (p = 0.04) . The identification of toxigenic ribotype 002 in 2009 was temporally related to a significant increase in both the incidence of toxigenic C. difficile from 0.53 to 0.95 per 1,000 admissions (p < 0.001) and the rate of positive detection from 4.17% to 6.28% (p < 0.001) between period 1 (2004-2008) and period 2 (2009). This finding should alert both the physician and the infection control team to the establishment of and possible outbreaks by ribotype 002 in our hospitals, as in the case of ribotype 027.

Marked increase of Pseudomonas aeruginosa serotype 012 in Belgium since 1982

May 1988


30 Reads

Routine typing was performed on a total of 7089 Pseudomonas aeruginosa strains isolated in 16 Belgian hospitals in the period from 1977 to 1986. The annual number of strains received ranged from 318 to 1346. The incidence of serotype O:12 was less than 2% until 1981 when it rose to 4%, steadily increasing to become the predominant serotype in 1984 (22%), 1985 (18%) and 1986 (22%). Since 1980 the O:12 isolates have exhibited characteristic patterns on pyocin and phage typing, 89% of O:12 isolates belonging to pyocin types 1, 39, 43, 45 or 105, whereas only 51% of isolates of other serotypes belonged to those pyocin types. Ninety-three per cent of serotype O:12 isolates belonged to phage types 68/119x, 68 or 119x, or were non-typable, whereas only 24.37% of other serotypes isolates exhibited these phage patterns. These distinctive patterns of pyocin and phage types suggest a high degree of homogeneity within the O:12 strains isolated in recent years in Belgium. Multi-centre or country-wide survey of Pseudomonas aeruginosa strains isolated in hospitals using epidemiological markers may be of value in identifying a sudden increase in epidemic strains.

Adoptive immunity mediated by HLA-A*0201 restricted Asp f16 peptides-specific CD8+T cells against Aspergillus fumigatus infection

June 2012


64 Reads

Aspergillus fumigatus (A. fumigatus) is the most common pathogen of invasive aspergillosis (IA), a life-threatening infection in immunocompromised patients. Recent findings revealed that CD8+ T cells can mediate cytotoxic activity against A. fumigatus. Here, we bioinformatically identified three HLA-A*0201-restricted peptides from Asp f16, an A. fumigatus antigen which was previously shown to be involved in T cell immunity. Our immunological results demonstrated that these peptides can potently induce cytotoxic T lymphocyte (CTL) response in CD8+ T cells, thus, damaging the conidia and hyphae of A. fumigatus. Moreover, the Asp f16 peptides can also raise Th1 cell-like response, as measured by interferon-γ (IFN-γ) enzyme-linked immunosorbent spot (ELISPOT). Furthermore, we established an invasive pulmonary aspergillosis model in HLA-A*0201 transgenic mice. Adoptive transfer of Asp f16 peptides-specific CTL significantly extended the overall survival time in the A. fumigatus-infected immunocompromised mice. In conclusion, our results demonstrate that the Asp f16 peptides might provide immunity against invasive A. fumigatus infection.

A multiplex, internally controlled real-time PCR assay for detection of toxigenic Clostridium difficile and identification of hypervirulent strain 027/ST-1

September 2011


55 Reads

The purpose of this study was to validate a multiplex real-time PCR assay capable of detecting toxigenic Clostridium difficile and simultaneously identifying C. difficile ribotype 027/ST-1 by targeting the toxin genes tcdA, tcdB and cdtA in one reaction and in a separate reaction identifying the Δ117 deletion in tcdC associated with ribotype 027/ST-1. PCR was done prospectively on 704 samples routinely submitted to our department and results were compared to results of toxigenic culture. Sequencing of tcdC, multi locus sequence typing (MLST) and PCR ribotyping were done on cultured isolates to confirm the correct identification of the Δ117 deletion in tcdC and C. difficile ribotype 027/ST-1, respectively. The PCR assay displayed a sensitivity, specificity, PPV and NPV of 99.0%, 97.4%, 87.4% and 99.8%, respectively, compared to toxigenic culture on 665 samples evaluable both by PCR and culture. Sequencing of tcdC, ribotyping and MLST of cultured isolates validated the genotyping assay and confirmed the ability of the assay to correctly identify C. difficile ribotype 027/ST-1 in our current epidemiological setting. We describe the use of a combination of two separate PCR assays for sensitive and specific detection of toxigenic C. difficile and presumptive identification of C. difficile 027/ST-1.

Table 2 Diagnostic parameters. Frequencies and percentages are report- ed for categorical variables. Sample sizes range between 207 and 210 except for albumin, which has a sample size of n=162
Comparison of lactoferrin median levels between diagnostic groups. Medians are noted with a bold line and bars and dots show lower and upper quartiles. Units for lactoferrin are shown in parenthesis. p values not included in the plot are above 0.05
Comparison of white blood cell (WBC) median counts in the diagnostic groups. Medians are noted with a bold line and, bars and dots show lower and upper quartiles. Units for WBC count are shown in parenthesis p values not included in the plot are above 0.05
characteristics. Mean and standard deviation are reported for continuous variables. The skew for all continuous variables was below 1.5 in magnitude. Sample sizes ranged from 206 to 210 for these measures
Ribotype 027 Clostridium difficile infections with measurable stool toxin have increased lactoferrin and are associated with a higher mortality

January 2014


82 Reads

We evaluated clinical and diagnostic indicators of severe C. difficile infection (CDI) and their association with poor clinical outcome. A total of 210 patients positive according to PCR (toxin B: tcdB) were included, with patients having a median age of 62 years and a Charlson co-morbidity index (CI) score of 5. Ninety-one percent (n = 191) were positive by toxigenic culture and 61 % (n = 129) had stool toxin. Toxin-positive patients had significantly higher fecal lactoferrin (mean 316 μg/g versus 106 μg/g stool; p < 0.0001). Forty percent of patients (n = 85) were infected with ribotype 027 and significantly more of these patients had measurable stool toxin (79 % vs. 50 %; p < 0.0001). The mean fecal lactoferrin was significantly higher for toxin-positive 027 CDI compared with the 027 toxin-negative group (317 vs 60 μg/g; p = 0.0014). Ribotype 027 CDI with stool toxin showed a higher all-cause, 100-day mortality compared with non-027 with stool toxin (36 % vs 18 %; p = 0.017). Logistic regression univariate analysis for odds ratio (OR) and p values revealed that age (OR = 1.1), intensive care unit treatment (OR = 2.7), CI (OR = 1.2), 027 CDI (OR = 2.1), white blood cell count (OR = 1.0), albumin level (OR = 0.1), and stool toxin-positive 027 CDI (OR = 2.5) were significantly associated with 100-day mortality (p < 0.05). In conclusion, CDI PCR-positive patients with 027 infection and stool toxin have increased lactoferrin and are at an increased risk of death.

Rapid detection of the Clostridium difficile ribotype 027 tcdC gene frame shift mutation at position 117 by real-time PCR and melt curve analysis

April 2009


115 Reads

The emergence of the hypervirulent strain Clostridium difficile PCR ribotype 027 has increased the necessity for rapid C. difficile typing tests for clinical and epidemiological purposes. We developed a rapid real-time polymerase chain reaction (PCR) test for the detection of C. difficile. As the target, we chose the tcdC gene, which encodes for a negative regulator in toxin production. A deletion at position 117 of the tcdC gene, which is associated with severe tcdC truncation, is well conserved in all PCR ribotype 027 isolates. Probe sequences of the real-time PCR test were designed to result in distinct melt profiles for sequence variations at positions 117 to 120 of the tcdC gene. The tcdC gene deletion at position 117 was easily detected with real-time PCR and melt curve analysis in all C. difficile ribotype 027 isolates. In five non-027 strains and 46 hospitalised patient samples, melt curve analysis detected no deletion. PCR results were confirmed by DNA sequencing. The combination of real-time PCR and melt curve analysis is a rapid and accurate method for the detection of C. difficile DNA and simultaneous screening for the tcdC gene deletion at position 117, which is closely related to the C. difficile PCR ribotype 027 strain.

demographics and culture results for the study popu- lation. The percentage of patients for each criterion is shown, along with the number of patients presented in parentheses 
Elevated lactoferrin is associated with moderate to severe Clostridium difficile disease, stool toxin, and 027 infection

June 2013


645 Reads

We evaluated blood and fecal biomarkers as indicators of severity in symptomatic patients with confirmed Clostridium difficile infection (CDI). Recruitment included patients with CDI based on clinical symptoms and supporting laboratory findings. Disease severity was defined by physician's assessment and blood and fecal biomarkers were measured. Toxigenic culture done using spore enrichment and toxin B detected by tissue culture were done as confirmatory tests. Polymerase chain reaction (PCR) ribotyping was performed on each isolate. There were 98 patients recruited, with 85 (87 %) confirmed cases of toxigenic CDI (21 severe, 57 moderate, and seven mild), of which 68 (80 %) were also stool toxin-positive. Elevated lactoferrin (p = 0.01), increased white blood cell (WBC) count (p = 0.08), and low serum albumin (p = 0.03) were all associated with the more severe cases of CDI. Ribotype 027 infection accounted for 71 % of severe cases (p < 0.01) and patients with stool toxin had significantly higher lactoferrin levels and WBC counts (p < 0.05). Our findings show that elevated fecal lactoferrin, along with increased WBC count and low serum albumin, were associated with more severe CDI. In addition, patients infected with ribotype 027 and those with stool toxin had significantly higher fecal lactoferrin and WBC counts.

Impact of ribotype 027 on Clostridium difficile infection in a geriatric department

April 2013


33 Reads

The purposes of this study were to describe the epidemiology (2001-2009) of Clostridium difficile infections (CDI) in a geriatric department and to compare the clinical data of patients infected with a 027 or non-027 strain. We retrospectively identified all geriatric patients with CDI and analysed the clinical and microbiological data of 133 patients for whom a ribotype was available between March 2003 and December 2009. The incidence of CDI in our geriatric department increased from 0.2 per 100 admissions in 2001 to 8.1 in 2004 and decreased to 1.3 in 2008 before a new rise to 2.1 in 2009. The percentage of ribotype 027 decreased from 2007 but it remained the most prevalent ribotype during the years 2007-2009, with a greater dispersion of ribotypes. The mean age of the patients was 84 years and the median Charlson index was 6.0. Previous use of fluoroquinolones was a significant risk factor for developing a CDI with an 027 strain (p = 0.001). Cure was significantly lower in the 027 group (p = 0.003). The total attributable mortality was 24.1 %. A multiparametric model showed that attributable mortality was influenced by the ribotype 027 (p = 0.037), the severity of clinical symptoms (p = 0.001) and the type of treatment (p = 0.002). Oral vancomycin had a protective effect against mortality. Attention should be paid to elderly patients developing a CDI, especially after the administration of fluoroquinolones. Oral vancomycin could be recommended as the first-line agent not only to protect against recurrence or severe CDI, but to diminish the attributable mortality risk.

Bioassay for A-56268 (TE-031) and identification of its major metabolite, 14-hydroxy-6-O-methyl erythromycin

March 1988


16 Reads

A-56268 is a new macrolide which is generally two-fold more potent than erythromycin. A new bioassay is described in which plasma samples are extracted with acetonitrile prior to bioassay. The concentration range for the assay is between 0.05-4.0 micrograms/ml, and the concentrations measured are within 6% of those measured by high-power liquid chromatography. An active metabolite which is as active as erythromycin was identified in the plasma. The plasma half-life and area under the plasma curve values of A-56268, as determined by bioassay, were significantly greater than those of erythromycin.

In vitro activity of tosufloxacin (A-60969) and clarithromycin (A-56268, TE-031) against resistant Haemophilus influenzae, Streptococcus pneumoniae and Branhamella catarrhalis isolates

June 1990


9 Reads

The activity of tosufloxacin (A-60969), a new oral quinolone, and clarithromycin (A-56268, TE-031), a new oral macrolide, was compared in vitro to that of other oral quinolones and beta-lactam antimicrobial agents against clinical isolates of ampicillin and/or chloramphenicol resistant Haemophilus influenzae, penicillin resistant Streptococcus pneumoniae and beta-lactamase producing Branhamella catarrhalis. Results were compared to those for sensitive isolates. Tosufloxacin was the most active compound against Haemophilus influenzae and was more active than ciprofloxacin or ofloxacin against all strains of Streptococcus pneumoniae. Tosufloxacin was also more active than any of the beta-lactam drugs tested against penicillin resistant or relatively penicillin resistant isolates. Clarithromycin was the most active compound tested against both penicillin sensitive and penicillin resistant Streptococcus pneumoniae, and was as active as ciprofloxacin against Branhamella catarrhalis. In view of the favourable in vitro activity against common bacterial respiratory pathogens, tosufloxacin should be considered for clinical trials in adults with respiratory tract infections, while clarithromycin might be useful in treatment of infection with these organisms in all age groups.

Activity of the fourth generation cephalosporin FK-037 against methicillin-resistantStaphylococcus aureus under conditions maximizing PBP2′ production

January 1995


8 Reads

To investigate the in vitro activity of the fourth generation cephalosporin FK-037, MICs were determined for 80 strains of methicillin-resistant Staphylococcus aureus from 11 countries. Methicillin and cefamandole served as comparators. The method ensured good expression of PBP2' by use of a large inoculum, salt supplement and incubation for 48 hours at 30 degrees C. FK-037 was twice as active as cefamandole against both strains with high-level and strains with low-level methicillin resistance (geometric mean MICs 23.4 and 10.8 mg/l, respectively).

In vitro activity of FK-037, a novel parenteral cephalosporin, against bacterial isolates from neutropenic cancer patients

September 1994


9 Reads

The in vitro activity of FK-037, a novel parenteral cephalosporin, was compared to that of ceftazidime, aztreonam and piperacillin (agents often used in empiric regimens in cancer patients) against recent bacterial isolates from patients with cancer. FK-037 was either equal to or 2 to 16-fold more active than the comparative agents against members of the Enterobacteriaceae. It was also active against Acinetobacter spp., Aeromonas spp., Pseudomonas aeruginosa, and other Pseudomonas spp. Xanthomonas maltophilia and Alcaligenes denitrificans were relatively resistant to all four agents. FK-037 was also 4 to 16-fold more active against most gram-positive organisms (including some methicillin-resistant staphylococci) than was ceftazidime. Enterococcus spp., Listeria monocytogenes and Staphylococcus haemolyticus were relatively resistant to FK-037 and ceftazidime. Overall, FK-037 has a broad antimicrobial spectrum that includes the majority of gram-positive and gram-negative isolates.

Multicentre comparative study on the antibacterial activity of FK-037, a new parenteral cephalosporin

April 1995


16 Reads

The in vitro antibacterial activity of FK-037, a new parenteral cephalosporin structurally related to cefpirome and cefepime, was compared with that of cefotaxime, ceftazidime, aztreonam, cefpirome, cefepime, imipenem and meropenem against 1,837 clinical isolates obtained from three Spanish hospitals. FK-037 inhibited 90% of Enterobacteriaceae isolates at < or = 0.25 microgram/ml, with the exception of Enterobacter aerogenes (MIC90 1 microgram/ml), Enterobacter cloacae and Citrobacter freundii (MIC90 8 micrograms/ml). In cefotaxime- and ceftazidime-resistant Klebsiella pneumoniae strains producing SHV-2 and SHV-6 beta-lactamases, the activity of FK-037, cefpirome and cefepime was similar (MIC range 0.25-32 micrograms/ml). In Enterobacteriaceae strains hyper-producing chromosomally inducible beta-lactamases, FK-037 (MIC90 range, 0.25-8 micrograms/ml) was 8- to 16-fold more active than cefotaxime and ceftazidime but two- to eightfold less active than cefpirome and cefepime. FK-037 and cefpirome were twofold more active than ceftazidime and cefepime against Pseudomonas aeruginosa isolates, with MIC90 values of 16 micrograms/ml. The activity of FK-037, cefpirome and cefepime was two- to eightfold lower in ceftazidime-resistant derepressed Pseudomonas aeruginosa mutants. FK-037 (MIC range, 0.12-2 micrograms/ml) and the other beta-lactam agents tested were active against methicillin-susceptible staphylococci; however, only cefpirome and, particularly, FK-037 (MIC90 of 32 micrograms/ml) displayed some activity against methicillin-resistant strains. In penicillin-susceptible, -intermediate and -resistant Streptococcus pneumoniae isolates, the MIC90s of FK-037 were 0.03, 0.5 and 1 microgram/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Fig. 1 Population analysis profiles (PAP) of methicillin-resistant Staphylococcus aureus (MRSA) strains that were positive by the macro Etest (MET). Isolates Sa400, Sa300, Sa061 and Sa616 were confirmed to be heteroresistant vancomycin-intermediate S. aureus (hVISA); strains Sa847 and Sa393 did not show heteroresistant subpopulations. Controls included strain Mu3 (h-VISA) and ATCC29213 (susceptible isolate) 
Table 2 Phenotypic and genotypic characteristics of the macro Etest (MET)-positive isolates submitted to population analysis profiles (PAP) 
Table 3 Phenotypic and genotypic characterisation of the principal spa types among MRSA 
Vancomycin-heteroresistant phenotype in invasive methicillin-resistant Staphylococcus aureus isolates belonging to spa type 041

July 2010


127 Reads

The aim of this study was to characterise invasive methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) strains from Italy and to investigate the presence of heteroresistant vancomycin-intermediate S. aureus (h-VISA). Eighty-two MSSA and 66 MRSA strains obtained from 19 laboratories were submitted to in vitro susceptibility testing; MRSA strains were also analysed by the macro Etest (MET) and vancomycin population analysis profiles (PAP) to detect the presence of h-VISA. Genotyping included the detection of agr locus, SCCmec typing, spa typing and multilocus sequence typing (MLST). By Etest, 66% of all isolates showed a minimum inhibitory concentration (MIC) >or=1.5 microg/ml and two MRSA strains were categorised as VISA (MIC = 3 microg/ml). Twelve MRSA strains were positive by MET; of these, 9 (14% of all MRSA) were confirmed as h-VISA by PAP. MRSA strains were assigned to 14 spa types, with t001, t008 and t041 including 77% of the isolates. The most common spa type, t041, characterised as ST228/273-MRSA-I (CC5) and comprising 24 isolates, included one VISA and eight h-VISA. This is the first description of a close association between h-VISA and t041, a spa type common in Italy and in other European countries, that highlights the importance of molecular typing to identify clones of special clinical relevance.

Table 1 : Patient demographics and baseline characteristics of AIDS patients with cytomegalovirus reti- nitis. 
Combination of ganciclovir and granulocyte-macrophage colony-stimulating factor in the treatment of cytomegalovirus retinitis in AIDS patients. The ACTG 073 Team

January 1994


109 Reads

The efficacy and safety of a combination of ganciclovir plus GM-CSF was evaluated in AIDS patients with cytomegalovirus retinitis. In phase A, patients were randomized to receive ganciclovir, 5 mg/kg every 12 h for 14 days followed by 5 mg/kg daily, with (n = 24) or without (n = 29) GM-CSF (1-8 micrograms/kg daily subcutaneously) to maintain absolute neutrophil counts between 2500 and 5000 cells/microliters. In phase B, after 16 weeks zidovudine was added to the regimen of 16 patients receiving ganciclovir plus GM-CSF and 20 receiving ganciclovir alone. At this stage, GM-CSF was added to the treatment protocol of any patient receiving ganciclovir plus zidovudine who became neutropenic. In phase A, patients in the ganciclovir plus GM-CSF group had significantly higher neutrophil counts than ganciclovir-alone patients (p = 0.0001). Overall, 12.5% of patients treated with GM-CSF developed neutropenia (absolute neutrophil counts < 500/microliters phase A and < 750/microliters phase B) compared with 45% of patients treated without GM-CSF. GM-CSF patients missed 10 of a possible 4705 scheduled doses of ganciclovir compared with 34 missed doses of a possible 6584 in the ganciclovir-alone group (p = 0.011). There was a trend, although not statistically significant, for patients in the GM-CSF group to experience delayed progression of their retinitis.(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro activity of Ro 09-1428 compared to other cephalosporins

September 1991


17 Reads

The in vitro activity of Ro 09-1428, a new catechol-type parenteral cephalosporin, was compared to that of ceftazidime, E-1040, cefpirome and cefepime against gram-positive and gram-negative organisms. Ro 09-1428 inhibited group A streptococci at less than or equal to 0.12 micrograms/ml, and group B, C and G streptococci and Streptococcus pneumoniae at 0.5 micrograms/ml, whereas for Staphylococcus aureus Ro 09-1428 had MICs of 8-16 micrograms/ml similar to ceftazidime and E-1040. Against Pseudomonas aeruginosa Ro 09-1428 was the most active agent, inhibiting isolates at less than or equal to 0.12-2 micrograms/ml, and inhibited ceftazidime-resistant isolates. The majority of Escherichia coli, Klebsiella spp., Proteus mirabilis, Citrobacter diversus, Providencia, Salmonella and Shigella were inhibited by less than or equal to 0.5 micrograms/ml as with the other cephalosporins. For most Citrobacter freundii and Enterobacter cloacae Ro 09-1428 had higher MICs of 4-16 micrograms/ml; most ceftazidime-resistant isolates of these species were resistant. Anaerobes, enterococci and Listeria monocytogenes were resistant to Ro 09-1428. Ro 09-1428 was not hydrolyzed by TEM-1, TEM-2, Staphylococcus aureus PC-1, Moraxella catarrhalis Bro-1, Enterobacter P-99, Pseudomonas aeruginosa Sabath-Abraham or Klebsiella beta-lactamases, but was hydrolyzed by TEM-3, TEM-7 and TEM-9. Ro 09-1428 was markedly less active at an acid pH.

In Vitro Activity of the New Echinocandin Antifungal, MK-0991, against Common and Uncommon Clinical Isolates of Candida Species

May 1999


9 Reads

A broth macrodilution method, performed as recommended by the National Committee for Clinical Laboratory Standards, was used for comparative testing of the new echinocandin antifungal agent MK-0991 and fluconazole against 50 yeast isolates belonging to 12 species of Candida. MK-0991 was shown to be highly effective against both fluconazole-susceptible and -resistant Candida spp., yielding minimum inhibitory concentrations ranging from < or = 0.19 to 0.78 microg/ml. Fungicidal activity was exerted at < or = 1.5 microg/ml for 73% of the isolates tested. This study suggests that MK-0991 has significant potential for clinical development.

Effects of caspofungin (MK-0991) and anidulafungin (LY303366) on phagocytosis, oxidative burst and killing of Candida albicans by human phagocytes

September 2004


23 Reads

The objective of the present study was to investigate the influence of the new echinocandins caspofungin (MK-0991) and anidulafungin (LY303366) on human phagocytes. Phagocytosis, oxidative burst and intracellular killing of Candida albicans were analyzed by flow cytometry. Neither caspofungin nor anidulafungin significantly influenced phagocytosis. Only caspofungin significantly influenced oxidative burst after 15 min of incubation ( P<0.05). Both caspofungin and anidulafungin improved intracellular killing rates of C. albicans after 2 h of incubation (42.4% and 43.2%, respectively, compared to 37.9% in controls; P<0.05). In conclusion, caspofungin significantly improves oxidative burst and intracellular killing, which may be advantageous for clinical therapy.

Fig. 1 Area under the curve (AUC) of the receiver-operating characteristic (ROC) curves of galactomannan (GM) and/or (1,3)-β- D-glucan (BG) determinations in serum for: a proven IA cases; b all  
Table 1 Baseline characteristics of 98 critically ill patients at risk of invasive fungal disease 
Table 3 Characteristics of critically ill patients at risk of IFD, and microbiological and serological data 
Prospective study in critically ill non-neutropenic patients: Diagnostic potential of (1,3)-β-D-glucan assay and circulating galactomannan for the diagnosis of invasive fungal disease

August 2011


256 Reads

Diagnosis of invasive fungal disease (IFD) in patients under intensive care is challenging. Circulating biomarkers, (1,3)-β-D-glucan (BG) and galactomannan (GM), were prospectively assessed in 98 critically ill patients at risk of IFD. There were 11 cases of invasive aspergillosis (IA; 4 proven and 7 probable), 9 cases of proven invasive candidiasis (IC), 1 case of mixed proven IC and probable IA, 1 case of proven zygomycosis, and 1 case of mixed mycelial proven IFD. In all IA cases there was no significant difference when the area under the receiver operating characteristic curve (AUC) of GM (0.873 [95%CI, 0.75-0.99]) and BG (0.856 [95% CI, 0.71-0.99]) were compared (p = 0.871). The AUC for BG in IC and for the rest of the IFD cases was 0.605 (95% CI, 0.39-0.82) and 0.768 (95% CI, 0.63-0.90) respectively. Positive BG (40%) predated blood culture (n = 3) and abdominal pus (n = 1) a mean of 3.25 days before Candida was grown. In patients with IFD caused by molds, BG appeared a mean of 5.65 days before culture results. For the diagnosis of patients at risk of IC, BG has shown a high NPV (94.5%), with positive results also predating blood cultures in 30% of patients. In conclusion, early BG results permit a timely initiation of antifungal therapy in patients at risk of IFD.

Efficacy of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)-cytosine and 9-(1,3-dihydroxy-2-propoxymethyl)-guanine in the treatment of intracerebral murine cytomegalovirus infections in immunocompetent and immunodeficient mice

May 1993


7 Reads

The efficacy of HPMPC and DHPG against systemic and intracerebral murine cytomegalovirus (MCMV) infections was examined in immunocompetent NMRI mice and in mice with severe combined immunodeficiency (SCID). HPMPC proved to be far superior to DHPG in preventing mortality and growth retardation in MCMV-infected NMRI mice even when given as a single dose on the day of infection. In intraperitoneally infected SCID mice, HPMPC administered as a single dose of 2, 10, 20 or 50 mg/kg per week increased the survival period of the mice by 22, 49, 77 and 156 days, respectively. In contrast, DHPG at daily doses of 10, 20 or 50 mg/kg for five consecutive days every week did not delay death by more than 13, 17 and 21 days, respectively. About one week before the MCMV-infected SCID mice (treated with either DHPG or HPMPC) died, they developed signs of neurological disease and intranuclear inclusion-bearing cells were found in their brains. The virus that was recovered from the brains of these mice did not prove to be resistant to HPMPC or DHPG. Only the virus recovered from the brains of mice treated with HPMPC at a dosage of 50 mg/kg/week had a slightly decreased susceptibility to HPMPC. When HPMPC (50 mg/kg for 4 consecutive days) was administered to SCID mice at the time when neurological symptoms became apparent, death of the animals could be delayed by another 35 to 40 days.

Table 1 Distribution of the operation type case load 
Table 2 Microbiology of the 109 post-operative central nervous system infections (PCNSIs) 
Post-operative central nervous system infections after cranial surgery in China: Incidence, causative agents, and risk factors in 1,470 patients

December 2013


402 Reads

A post-operative central nervous system infection (PCNSI) is a dangerous complication after cranial surgery. Although a large number of neurosurgical procedures are performed in hospitals in China, PCNSI-related data from this country are rarely reported. To address this issue, we examined the incidence of PCNSI after cranial surgery, the potential risk factors, and the offending etiologic agents in a large Chinese population. The medical records and post-operative courses for patients >16 years of age who underwent elective or emergency cranial surgeries between May 2010 and May 2012 and who survived for >7 days were reviewed retrospectively. Pre-operative data, surgery-related records, and post-operative variables were evaluated as risk factors for PCNSI after cranial surgery. Among 1,470 surgeries, 1,340 were craniotomies and 130 involved the cerebrospinal fluid (CSF). There were 109 patients with PCNSIs, resulting in a total infection rate of 7.4 %. The dominant Gram-positive organism isolated (Staphylococcus aureus) was the most common pathogen isolated. Based on multivariate analysis, the risk of PCNSI was increased by a CSF leak [odds ratio (OR), 3.545; 95 % confidence interval (CI), 2.053-6.122; p < 0.001], CSF drainage of any kind (OR, 2.858; 95 % CI, 1.577-5.181; p = 0.001), subsequent short-term surgery (OR, 2.224; 95 % CI, 1.229-4.024; p = 0.008), and surgery duration (OR, 1.331; 95 % CI, 1.230-1.440; p < 0.001). PCNSI remains a critical problem for neurosurgeons in China. CSF leakage, CSF drainage of any kind, subsequent short-term surgery, and surgery duration were major risk factors, indicating that surgery-focused management might be the most effective way to minimize the risk for PCNSI after cranial surgery.

Top-cited authors