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Microbial profile and antibiotic susceptibility of culture-positive bacterial endophthalmitis
Abstract
To assess the distribution of microorganisms isolated from patients with bacterial endophthalmitis and their antimicrobial susceptibility.
Retrospective analysis of medical and microbiological records of patients with suspected diagnosis of endophthalmitis. The following information was assessed: number of presumed and culture-positive endophthalmitis cases, source of infection, microbiological result (aqueous and/or vitreous culture and Gram staining), microbial characterization and distribution, and antimicrobial susceptibility.
A total of 107 (46%) of 231 patients with bacterial endophthalmitis showed positive results by gram stain or culture. Of these, 97 (42%) patients were positive for culture only. Most of them (62%) were secondary to a surgical procedure (postoperative), 12% were posttraumatic and 26% were secondary to an unknown source or the data were unavailable. A total of 100 microorganisms were isolated (38 aqueous and 67 vitreous samples) from the 97 culture-positive cases (91% were gram-positive and 9% were gram-negative). Coagulase-negative Staphylococcus(CoNS) (48%) were the most frequently isolated, followed by Stretococcus viridans(18%), and Staphylococcus aureus(13%). The antimicrobial susceptibility for CoNS was as follows: amikacin-91.6%, cephalothin-97.9%, ceftriaxone-50%, ciprofloxacin-62.5%, chloramphenicol-91.8%, gatifloxacin-79.5%, gentamicin-72.9%, moxifloxacin-89.5%, ofloxacin-70.8%, oxacillin-58.3%, penicillin-33.3%, tobramycin-85.4%, and vancomycin-100%.
Gram-positive bacteria were the major causes of infectious endophthalmitis in this large series, usually following surgery. CoNS was the most common isolate. Of interest, susceptibility to oxacillin and fourth-generation quinolones was lower than previously published.
... The rate of positive bacterial identification in cases of endophthalmitis is 44.4-46% using conventional culture methods, in which the specimen is directly applied onto nutrient agar and incubated to facilitate the growth of bacteria [5,6]. Rates of identification increase to approximately 50-70% when hemoculture bottles are used [7][8][9][10][11]. ...
... This was slightly lower than previous reports (44.4-46%) [5,6]. The present study included all cases of suspected acute bacterial endophthalmitis admitted to our hospital over the study period. ...
... Melo et al. [5] studied the microbial profiles of patients diagnosed with suspected endophthalmitis and found that 91% of bacteria in such cases were Grampositive. Among these cases, coagulase-negative staphylococci were the most common organisms (48%). ...
Background
Identification of bacterial pathogens in endophthalmitis is important to inform antibiotic selection and treatment decisions. Hemoculture bottles and polymerase chain reaction (PCR) analysis have been proposed to offer good detection sensitivity. This study compared the sensitivity and accuracy of a blood culture system, a PCR approach, and conventional culture methods for identification of causative bacteria in cases of acute endophthalmitis. Methods
Twenty-nine patients with a diagnosis of presumed acute bacterial endophthalmitis who underwent vitreous specimen collection at King Chulalongkorn Memorial Hospital were enrolled in this study. Forty-one specimens were collected. Each specimen was divided into three parts, and each part was analyzed using one of three microbial identification techniques: conventional plate culture, blood culture, and polymerase chain reaction and sequencing. The results of the three methods were then compared. ResultsBacteria were identified in 15 of the 41 specimens (36.5%). Five (12.2%) specimens were positive by conventional culture methods, 11 (26.8%) were positive by hemoculture, and 11 (26.8%) were positive by PCR. Cohen’s kappa analysis revealed p-values for conventional methods vs. hemoculture, conventional methods vs. PCR, and hemoculture vs. PCR of 0.057, 0.33, and 0.009, respectively. Higher detection rates of Enterococcus faecalis were observed for hemoculture and PCR than for conventional methods. Conclusions
Blood culture bottles and PCR detection may facilitate bacterial identification in cases of presumed acute endophthalmitis. These techniques should be used in addition to conventional plate culture methods because they provide a greater degree of sensitivity than conventional plate culture alone for the detection of specific microorganisms such as E. faecalis. Trial registrationThai Clinical Trial Register No. TCTR20110000024.
... are currently the most common etiologic agents of acute postoperative endophthalmitis. 6,7 In contrast, indolent organisms are usually responsible for chronic endophthalmitis, including Propionibacterium acnes and Corynebacterium spp. 4,6 However, it is well known that microorganisms can be introduced into the eye from the patient's external microbiota during surgery. ...
... 13 Detection of endophthalmitis and identification of the causative agent are therefore essential to ensure that rational treatment is given, 14 yet routine microbiologic diagnosis relies on time-consuming classical culture techniques that offer low sensitivity; indeed, the positivity rates range from 22% to 30% in the aqueous humor and from 40% to 69% in the vitreous humor. 15 Modern molecular techniques-such as polymerase chain reaction (PCR) combined with different post-PCR analyses-now allow for greater sensitivity and more rapid results 7,14,16 and are particularly useful when only a small amount of material is available (eg, aqueous humor) or if the patient has previously received antibiotic treatment. 14 In addition, molecular techniques are promising for the detection of organisms associated with chronic postoperative endophthalmitis because the samples are often small, difficult to culture, fastidious, or slow growing. ...
... This confirms that molecular techniques improve bacterial DNA detection by providing a more sensitive and rapid assessment compared with conventional microbiology. 7,14,16 This may be especially so with small samples (especially for aqueous humor), with those subject to antibiotic use before sampling, where the microorganism has fastidious growth requirements, and, of course, where there is sequestration of bacteria on solid surfaces. 14,27 However, in 2 of the ocular globes analyzed, DNA amplification, sequencing, and database comparison suggested that the identified microorganism was a probable environmental contaminant. ...
Purpose:
Postoperative endophthalmitis is a potentially sight-threatening complication of cataract surgery. However, the pathophysiological mechanisms are not completely understood. To study and evaluate the intraocular environment (aqueous and vitreous humors), the capsular tissue, and the intraocular lens (IOL) surfaces of normal eyes after long-term uncomplicated cataract surgery.
Design:
Experimental laboratory investigation.
Methods:
We studied 69 eyes donated for transplantation that had previously undergone cataract surgery with posterior chamber IOL implantation, and that had no recorded clinical history of postoperative inflammation. We assessed the intraocular environment (DNA traces and biofilm formation) by microbiological evaluation of intraocular fluids using conventional microbiology and molecular techniques, including assessment for the presence of microbes (biofilm formation) on the IOL surface by scanning electron microscopy and ultrastructural capsular remnants by transmission electron microscopy.
Results:
Isolated or aggregated cocci were probable in 18.8% of IOL optic surfaces (n = 13) studied by scanning electron microscopy, suggesting the presence of bacterial biofilm. In three intraocular fluid samples for IOLs with biofilm, we identified 16S rDNA by polymerase chain reaction and sequencing. No microbial contamination was found in intraocular fluids by conventional microbiological methods.
Conclusions:
Our data suggest the possibility of bacterial biofilm formation on the optic surface of IOLs in normal eyes after long-term uncomplicated cataract surgery even in the absence of clinical or sub-clinical symptomatology.
... Forty-one of the cases in this study (87 %) were Grampositive. A similar rate (90 %) was reported in the EVS [3] and elsewhere (63-91 %) [7][8][9][10]. CNS was grown from 22 samples in this study (47 %), representing the most common causative organism. ...
... CNS was grown from 22 samples in this study (47 %), representing the most common causative organism. This has been found in other centres, and in the EVS CNS represented 70 % of the culturepositive isolates [3,7,11]. CNS are the most prevalent commensal bacteria of skin and conjunctiva, being identified in 76 % of healthy individuals; with lower frequencies of Staphylococcus aureus (7 %) and Streptococcus spp. ...
... There are at present no data to support the use of more aggressive treatment strategies such as repeat intravitreal injection or vitrectomy/washout as a matter of routine for such cases. However, given the poor visual outcomes reported here and elsewhere, careful observation of Haemophilus-associated endophthalmitis is certainly warranted, and until further data is available, subsequent treatment should be guided by clinical judgement [2,3,5,7,28]. ...
Purpose
To review the microbiology of culture-positive cases of bacterial endophthalmitis, and to correlate this with visual outcomes.
Method
Case notes were reviewed for culture-positive cases of bacterial endophthalmitis over a period from November 1999 to June 2012. Cases were identified retrospectively using a local database. The Fisher exact test was used for statistical analysis.
Results
Of the 47 cases of culture-positive bacterial endophthalmitis identified, 81 % occurred postoperatively, 11 % followed intravitreal injection, 6 % had an endogenous source and 2 % followed ocular trauma. Eighty-seven percent of bacteria cultured were Gram-positive. The most commonly identified organisms were coagulase-negative Staphylococci (47 %) and Streptococcus spp. (30 %). Patients were treated with intravitreal vancomycin and either amikacin or ceftazidime. All Gram-negative isolates were sensitive to aminoglycosides and ceftazidime, and all Gram-positive isolates were vancomycin-sensitive. Final visual acuity (VA) was 6/12 or better in 41 % of cases and counting fingers (CF) or worse in 30 %. Endophthalmitis caused by Streptococcus spp. was associated with a poorer final VA (OR for CF or worse = 14.9, P
... The pathogenic isolates from monomicrobial ocular infections that were used for this study were one isolate each of the GPC Staphylococcus epidermidis, Staphylococcus hominis and Streptococcus pneumoniae; GPB Corynebacterium diphtheriae; GNB non-fermenters Pseudomonas aeruginosa, Pseudomonas stutzeri and Acinetobacter baumannii; GNB members of Enterobacteriaceae such as Klebsiella pneumoniae and Serratia ficaria; and fungi Aspergillus flavus and Fusarium solani. Coagulase negative Staphylococcus is one of the commonest ocular GPC pathogens, of which again S. epidermidis is the commonest worldwide [17,18]. S. pneumoniae is also a common ocular pathogen with high virulence and frequently poor outcomes [19]. ...
... The authors specifically chose the study isolates from microbiologically proven monomicrobial ocular infections, so that any change in the antimicrobial susceptibility of these single pathogens in polymicrobial settings compared with their monomicrobial results could be attributed to their polymicrobial interactions alone. S. epidermidis is one of the commonest GPC isolated, while P. aeruginosa is one of the commonest GNB isolated in ocular infections [17,18,20]. The results of the present experiments show that the general assumption that microbial interactions in polymicrobial infections almost always lead to increased AMR for the co-infectants appears to be untrue. ...
Purpose: Investigate the effect of polymicrobial interactions on antimicrobial resistance (AMR) of ocular pathogens in polymicrobial settings, compared with monomicrobial infections. Methods: Polymicrobial interactions were labeled as antagonistic, synergistic or indifferent based on a reduction, an increase or no change, respectively, in antibiotics' MIC by the Vitek 2 compact system, compared with monomicrobial pathogens. Results: Staphylococcus epidermidis showed antagonistic polymicrobial interactions (22.6%); Pseudomonas aeruginosa showed synergistic interactions (62.5%); multidrug-resistant Acinetobacter baumannii showed increased susceptibility to select antibiotics; Serratia ficaria (inherently colistin resistant) became colistin-susceptible in polymicrobial combinations. Conclusion: Both antagonistic and synergistic interactions exist among human pathogens in polymicrobial settings. Gram-positive pathogens had significantly higher antagonistic polymicrobial interactions (increased MICs: 20.4%) compared with Gram-negative ones (synergistic: 59.4%).
... In this report, we analyze a rare case of acute anterior uveitis in which the characteristic ocular symptom was the sudden appearance of a large amount of exudate in the anterior chamber accompanied by a sudden decrease in visual acuity. Endophthalmitis is one of the most devastating eye infections and may lead to irreversible blindness in the infected eye within hours or days of symptom onset [10]. According to the patient's history, auxiliary examinations and changes in signs during treatment, their disease was not consistent with the development and characteristics of endophthalmitis. ...
Purpose
This report describes a rare case of acute uveitis with severe anterior chamber inflammation due to abnormal glucose and lipid metabolism.
Case presentation
A 31-year-old male patient complained of redness in the right eye with decreased visual acuity for 3 days. Ocular examination revealed a milky white clouding of the right anterior chamber of the eye. Two clusters of yellowish-white exudates were visible on the surface of the iris in the upper nasal and temporal areas in addition to elevated intraocular pressure. He had a previous diagnosis of type 2 diabetes mellitus (T2DM). Laboratory tests suggested hyperlipidemia and ketoacidosis. After admission, topical glucocorticoids, mydriasis, and intraocular pressure-lowering drugs combined with hypoglycemic and lipid-lowering therapy and fluid replacement therapy were given immediately. After 10 days of treatment, the uveitis and systemic condition of the right eye were effectively controlled and improved.
Conclusion
Abnormal glucose and lipid metabolism leads to impairment of the blood-aqueous barrier, which causes a severe uveitis response in the anterior chamber. After the use of topical steroids and mydriatic eye drops combined with systemic hypoglycemic and lipid-lowering interventions, the condition was significantly relieved.
... These etiologies are also the most common causes of endophthalmitis seen in other hospitals in the United States and globally. [59][60][61][62][63][64][65][66] Samples collected from 12 culture-proven endophthalmitis cases were processed using our novel diagnostic approach. We found complete agreement between culture results and molecular identification at the genus level. ...
Purpose:
Intraocular infections are sight-threatening conditions that can lead to vision loss. Rapid identification of the etiologies plays a key role in early initiation of effective therapy to save vision. However, current diagnostic modalities are time-consuming, lack sensitivity and inclusiveness. We present here a newly developed comprehensive ocular panel designed to improve diagnostic yields and provide a tool for rapid and sensitive pathogen detection.
Design:
Experimental laboratory investigation.
Methods:
A panel containing 46 pathogens and 2 resistance/virulence markers that are commonly detected in intraocular infections was developed. Genomic targets were scrutinized for stretches predicted to be specific for a particular species while being conserved across different strains. A set of primers for sample enrichment, and two 50mer NanoString compatible probes were then designed for each target. Probe-target hybrids were detected and quantified using the NanoString nCounter SPRINT Profiler. Diagnostic feasibility was assessed in a pilot clinical study testing samples from infectious retinitis (n=15) and endophthalmitis (n=12) patients for which the etiologies were confirmed by PCR or culture.
Results:
Analytical studies demonstrated highly sensitive detection of a broad spectrum of pathogens, including bacteria, viruses and parasites, with limits of detection being as low as 2.5 femtograms per reaction. We also found excellent target specificity, with minimal cross-reactivity detected. The custom-designed NanoString ocular panel correctly identified the causative agent from all clinical specimens positive for a variety of pathogens.
Conclusion:
This highly multiplexed panel for pathogen detection offers a sensitive, comprehensive, and uniform assay run directly on ocular fluids that could significantly improve diagnostics of sight-threatening intraocular infections.
... Conjunctival bacterial flora could be source of infection if introduced into the eye during intraocular surgery leading to postoperative endophthalmitis, common organisms are Coagulase-negative staphylococcus, Staphylococcus aureus, and Streptococcus species (4)(5)(6). An analysis of vitrectomy specimens in 82% of patients with post-operative endophthalmitis revealed that the organisms isolated were genetically indistinguishable from the isolates recovered from the patient's eyelid, conjunctiva or nose (7). ...
Background: Bacterial contamination from conjunctiva of surgical eye patients may lead to infective endophthalmitis and identification of conjunctival isolates and their antibiotic sensitivity would help in planning appropriate prophylactic interventions. The objective was to determine the predominant conjunctiva bacterial flora in patients scheduled for cataract surgery and their antibiotic sensitivity pattern. Materials and methods: The study comprised of 275 consecutive adult patients who underwent cataract surgery from January to April 2017 and met the inclusion criteria. The participants' socio-demographic characteristics, social, and medical history were obtained through interviewer-administered Questionnaire. Conjunctival swabs were collected from patients prior to cataract surgery and used to inoculate blood agar and chocolate agar plates and then incubated at 37°C for 18-24 hours. Bacterial identification was then carried out using standard. methods. Susceptibility testing was done on Mueller Hinton agar based on modified Kirby Bauer methods using the following drugs; Chloramphenicol, Ciprofloxacin, Ofloxacin, Levofloxacin, Imipenem, Cefuroxime, Ceftriaxone, Ceftazidime, Amikacin, Gentamicin, Tetracycline and Penicillin. Epi Info 7 software was used for univariate and bivariate data analysis as appropriate. Results: Bacterial growth was seen in 118 (42.9%) of the patients. The bacteria identified were: Staphylococcus epidermidis (48.3%); Staphylococcus aureus (44%); Gram positive bacilli (6%) and Streptococcus species (1.7%). The isolates were susceptible to Imipenem, Cefuroxime, Gentamicin, Chloramphenicol, Amikacin and Levofloxacin. Resistance to Tetracycline and Penicillin was also recorded. A statistically significant relationship was found between age and culture status (p = 0.0192). Conclusion: The predominant bacteria on the conjunctival sac were Staphylococcus epidermidis and Staphylococcus aureus, which were sensitive to some commonly perioperative antibiotics like chloramphenicol and gentamicin. Keywords: Cataract surgery; Conjunctival flora; Antibiotic sensitivity
... is classic model provides a basis for the accurate use of antibiotics in later clinical trials [15]. However, the traditional model has the following limitations: (1) the positivity rate of bacterial culture results ranges from 40% to 70% [16], and can be negatively affected by the use of antibiotics during the perioperative period, insufficient specimen volume, low bacterial count in specimens, and suboptimal growth of micro-organisms in the experimental conditions [17]; (2) the pathogenic bacteria identified are not always the main pathogenic organisms, as some pathogenic bacteria grow more easily during the culture process, leading to biased results. is was observed in a prospective study, in which 36 patients with endophthalmitis were recruited and the vitreous or aqueous humor was extracted for metagenomic next-generation sequencing (mNGS) and microbiological culture. In one case, culture identified K. pneumoniae, but mNGS identified C. jeikeium and P. putida. ...
Infectious endophthalmitis is an important cause of vision loss worldwide. It is an inflammatory reaction caused by bacteria, fungi, and other micro-organisms and often occurs as a complication of intraocular surgery, especially following cataract surgery or intravitreal injection. The focus of the prevention and treatment of infectious endophthalmitis is the early detection of microbial flora, such as fungi or bacteria. Current identification methods for bacteria include Gram staining-based, culture-based, and polymerase chain reaction (PCR)-based methods. The matrix-assisted laser desorption/ionization time-of-flight mass spectrometry technology is now the standard identification method of bacteria and fungi after their isolation in culture. The remarkable sensitivity of PCR technology for the direct detection of micro-organisms in clinical samples makes it particularly useful in culture-positive and culture-negative endophthalmitis. Furthermore, PCR increases the rate of microorganism detection in intraocular samples by 20% and can provide a microbiology diagnosis in approximately 44.7–100% of the culture-negative cases. This review aims to introduce the development of different methods for the detection and identification of micro-organisms causing endophthalmitis through a literature review; introduce the research status of the first, second, and third-generation sequencing technologies in infectious endophthalmitis; and understand the research status of endophthalmitis microbial flora. For slow-growing and rare micro-organisms, high-throughput sequencing (HTS) offers advantages over conventional methods and provides a basis for the identification of pathogens in endophthalmitis cases with negative culture. It is a reliable platform for the identification of pathogenic bacteria of infectious endophthalmitis in the future and provides a reference for the clinical diagnosis and treatment of infectious endophthalmitis. The application of HTS technology may also be transformative for clinical microbiology and represents an exciting future direction for the epidemiology of ocular infections.
... It is often caused by infection, either as a consequence of intraocular surgery (post-operative endophthalmitis), penetrating injury (post-traumatic endophthalmitis), or spread of bacteria from a distant site of infection to the eye (endogenous endophthalmitis) [7]. Most cases of bacterial endophthalmitis are caused by coagulase-negative staphylococci (CoNS), Staphylococcus aureus and viridans group streptococci [8]. E. faecalis are infrequently isolated from post-operative endophthalmitis, but patients with post-operative enterococcal endophthalmitis have worse clinical outcomes compared with similar infections caused by CoNS and S. aureus [9]. ...
Enterococcus faecalis are hospital-associated opportunistic pathogens and also causative agents of post-operative endophthalmitis. Patients with enterococcal endophthalmitis often have poor visual outcomes, despite appropriate antibiotic therapy. Here we investigated the genomic and phenotypic characteristics of E . faecalis isolates collected from 13 patients treated at the University of Pittsburgh Medical Center Eye Center over 19 years. Comparative genomic analysis indicated that patients were infected with E . faecalis belonging to diverse multi-locus sequence types (STs) and resembled E . faecalis sampled from clinical, commensal, and environmental sources. We identified known E . faecalis virulence factors and antibiotic resistance genes in each genome, including genes conferring resistance to aminoglycosides, erythromycin, and tetracyclines. We assessed all isolates for their cytolysin production, biofilm formation, and antibiotic susceptibility, and observed phenotypic differences between isolates. Fluoroquinolone and cephalosporin susceptibilities were particularly variable between isolates, as were biofilm formation and cytolysin production. In addition, we found evidence of E . faecalis adaptation during recurrent endophthalmitis by identifying genetic variants that arose in sequential isolates sampled over eight months from the same patient. We identified a mutation in the DNA mismatch repair gene mutS that was associated with an increased rate of spontaneous mutation in the final isolate from the patient. Overall this study documents the genomic and phenotypic variability among E . faecalis causing endophthalmitis, as well as possible adaptive mechanisms underlying bacterial persistence during recurrent ocular infection.
... Endophthalmitis is an infection of the vitreous and/or aqueous by microbial agents like bacteria or fungi. If intraocular infections is caused by viruses or parasites, it is usually considered as a types of uveitis rather than endophthalmitis [1] . Endophthalmitis can be either exogenous, where microbes on the ocular surface or from an external source are introduced into the eye or endogenous where endophthalmitis is caused by hematogenous spread of pathogens during septicaemia. ...
... These results were similar to the study of Cornut in 17 cases of posttraumatic endophthalmitis [20]. The reports of Melo and Do Tan on endogenous bacterial endophthalmitis also showed a much higher rate of detecting pathogenic bacteria in vitreous specimens than aqueous specimens [21], [22]. ...
Background:
Pediatric endophthalmitis after open-globe injury had its clinical features, microbiological profile different from those in aldults. In Viet Nam, there was no report on the clinical and microbiological characteristics of pediatric posttraumatic endophthalmitis. Therefore, we conduct this study.
Aim:
To describe clinical features, ultrasound results, gram stain and culture results of endophthalmitis in pediatric open globe injuries.
Methods:
Prospective non-controlled study. Case series of 30 eyes presenting with post-traumatic endophthalmitis between 2015 and 2016 were reviewed.
Results:
Mean age was 8.03 ± 3.99 years. Metallic and organic etiologies were the most common causes for injuries (n = 11). 27 cases had penetrating corneal trauma. Dense opaque vitreous was seen in 25 eyes. Retinal necrosis < 1 quadrant and chorioretinal abscess > 1 quadrant were the most common fundus lesions. Dense vitreous opacity on ultrasound was most common (n = 28). Gram stain bacteria positivity was 93.3%, gram-positive was isolated in 63.3%. Vitreous samples were more often positive than aqueous (P = 0,002).
Conclusion:
Posttraumatic endophthalmitis in children is more common in boys aged 6-10 years and most often caused by injury with metallic and organic matters. Culture results were very low. Vitreous samples were more often positive than aqueous. Gram-positive bacteria were the most common causative organism.
... The efficiency of microbiological identification depends on the quality of specimen collection and transport. For post-operative endophthalmitis, reported culture positive rates range from 10 to 70%, which is greater than that from post-traumatic cases (Safneck, 2012;Durand, 1996;Kunimoto et al., 1999;Melo et al., 2011;Pathengay et al., 2004). This traditional method of bacterial culture techniques has drawbacks, as sample concentration may be time consuming, and inoculated media must be incubated immediately (Miller, 2016). ...
Bacillus cereus (B. cereus) endophthalmitis is a devastating intraocular infection primarily associated with post-traumatic injuries. The majority of these infections result in substantial vision loss, if not loss of the eye itself, within 12-48 h. Multifactorial mechanisms that lead to the innate intraocular inflammatory response during this disease include the combination of robust bacterial replication, migration of the organism throughout the eye, and toxin production by the organism. Therefore, the window of therapeutic intervention in B. cereus endophthalmitis is quite narrow compared to that of other pathogens which cause this disease. Understanding the interaction of bacterial and host factors is critical in understanding the disease and formulating more rational therapeutics for salvaging vision. In this review, we will discuss clinical and research findings related to B. cereus endophthalmitis in terms of the organism's virulence and inflammogenic potential, and strategies for improving of current therapeutic regimens for this blinding disease.
... The tendency of commensal microbes to form biofilms on the surface of intraocular lens is an important mechanism in the pathogenesis of post-cataract endophthalmitis that hiders the resolution of infection. Moreover, biofilm microbes are less likely to render culture positivity for the samples of aqueous and vitreous region (Melo et al. 2011). ...
The tremendous increase of multidrug-resistant bacterial pathogens has posed a serious threat in the management of infectious diseases. The human eye is known to commensally host the normal flora, including the opportunistic pathogens. The researchers have isolated and characterized numerous microbes belonging to different genera from healthy eye, including Pseudomonas, Propionibacterium, Acinetobacter, Corynebacterium, Brevundimonas, Staphylococcus, Sphyngomonas, Streptococcus, and many others. The human eye is virtually impermeable to microbes, despite being exposed to an array of microorganisms. Ocular infections usually occur through invasion of microbes that may come either from bloodstream or by breaching the ocular barriers. Both gram-negative and gram-positive bacteria are known to be responsible for ocular infections, with the major causative gram-positive bacteria being S. pneumoniae, coagulase-negative staphylococci, S. aureus, and S. pyogenes, with N. gonorrhoeae, Moraxella spp., P. aeruginosa, K. pneumoniae, E. coli, and Proteus spp. also being commonly isolated. Apart from the unchecked use of antibiotics and the dissemination of multidrug-resistant bacteria, development of biofilms on ocular surfaces are also a major concern for antimicrobial resistance. In biofilms, the antibiotics are less likely to penetrate, due to reduced rates of diffusions making some of the cells in biofilms more resistant, and eventually increasing the effective antibiotic dose by many folds in comparison to planktonic mode cells. In this chapter, a survey on the emergence and spread of MDR ocular bacterial pathogens has been made.
... In literature, direct inoculation and swab with subsequent convention medium have been employed for corneoscleral rim culture. [4,7,10,13,16,23] However, it seemed the positive rate would be underestimated if there were antibiotics in the preservation medium. Blood culture media (FAN), which contains agents for neutralization of antibiotic, seemed more logical for corneoscleral rim culture because of the antibiotics in the preservation medium. ...
BACKGROUND/PURPOSE: Postoperative infection is the most disastrous complication of penetrating keratoplasty (PK). Corneoscleral rim culture provided information regarding subsequent infections. Our aims were to identify the incidence of microbial contamination in donor corneas and to report the recovery of bacteria with two culture methods, i.e., conventional culture media after aerobic/anaerobic cotton swabs and blood culture media (Fastidious Antibiotic Neutralization [FAN]).
MATERIALS AND METHODS: A total of 118 patients underwent PK. Corneoscleral rim cultures were performed using aerobic/anaerobic culture cotton swabs (Transystem™, COPAN, Italia) with subsequent convention media and blood culture media (FAN bottle, BD BACTEC™, USA). The results of the different methods were reported and analyzed.
RESULTS: Microorganisms were recovered from 24 in total 118 cases (20.3%, n = 118), 14 from blood culture media (FAN) (11.8%, n = 118), 9 from conventional culture media after aerobic/anaerobic cotton swabs (7.63%, n = 118), and 2 from fungus culture (1.69%, n = 118). The most commonly identified pathogen was coagulase-negative Staphylococcus (CoNS) (n = 13, 54.2%), and more isolates of CoNS and staphylococcus aureus were recovered from blood culture media (FAN) than those from conventional culture media after aerobic/anaerobic cotton swabs (13 vs. 4,P= 0.05). Conversely, more nonfermentative Gram-negative bacilli were recovered from conventional culture media after aerobic/anaerobic cotton swabs. None of the 24 cases with positive corneoscleral rim cultures reported ocular infection for the recipients in at least 6 months' follow-up.
CONCLUSION: The conventional culture media after aerobic/anaerobic cotton swabs and blood culture media (FAN) did not yield identical isolates of bacteria. The blood culture media (FAN) could further yield Gram-positive bacteria in addition to those recovered from convention media. It seemed adding gentamicin and streptomycin could achieve bacteriostatic effect instead of the bactericidal effect. The administration of postoperative antibiotic in the recipient was suggested.
... Endophthalmitis cases caused by streptococcal species are associated with poor visual outcomes such as loss of light perception, evisceration, and enucleation [5][6][7][8][9][10][11]. In many cases, the VGS are the second most commonly identified causative agents of bacterial endophthalmitis after coagulase-negative staphylococci [8,[12][13][14][15][16]. Although the incidence of bacterial endophthalmitis is low, ocular surgeries and intravitreal injections of therapeutic agents are increasing, and the VGS have emerged as pathogens associated with infections following intravitreal injections [6, [17][18][19]. ...
The viridans group streptococci comprise multiple species and have gained more recognition in recent years as common etiologic agents of bacterial endophthalmitis. The purpose of this study was to identify the species of human endophthalmitis isolates of viridans streptococci and to characterize their potential virulence attributes. The species of 22 endophthalmitis strains of viridans streptococci were identified by Matrix Assisted Laser Desorption Ionization Time-of-Flight. Susceptibilities to 3 antibiotics commonly used for bacterial endophthalmitis were determined. The extracellular milieu of each strain was tested for cytotoxicity of retinal pigmented epithelial cells, hemolysis of sheep erythrocytes, and protease activity using gelatin zymography. Identified species were Streptococcus mitis/oralis, S. salivarius, S. vestibularis, S. parasanguinis, S. mutans, S. constellatus, and S. gordonii. One strain of S. pseudoporcinus was also identified. All strains were sensitive to vancomycin, 77% were resistant to amikacin, and 27% had intermediate resistance to ceftazidime. Extracellular milieu from all strains except one (S. pseudoporcinus) were largely devoid of toxicity to retinal pigmented epithelial cells and sheep erythrocytes. Twelve strains, 10 of which were S. mitis/oralis, produced protease activity. Interestingly, not all of the S. mitis/oralis strains were proteolytic. These findings highlight the diversity of virulence factor production in ocular strains of the viridans streptococci not only at the group level but also at the species level.
... In our study, the culture of inoculated blood culture bottles detected significantly more microorganisms compared with the culture of vitreous fluid by solid media and broth solutions. The conventional culture of native vitreous fluid on solid media as blood, chocolate and fungi selective agar has been reported to result in variable culture yield, resulting in 30-70% negative conventional culture results in this patient group [8,9]. Negative culture results have been discussed to be due to low microbial counts, spontaneously sterilising during the ocular inflammatory response for certain pathogens like CoNS or to non-infectious inflammation [10]. ...
The purpose of this investigation was to evaluate the performance of blood culture bottles in comparison to conventional microbiological culture techniques in detecting causative microorganisms of endophthalmitis and to determine their anti-infective susceptibility profiles. All consecutive cases with clinically suspected endophthalmitis in a university-based ophthalmology department between January 2009 and December 2016 were analysed in this retrospective comparative case series. Samples from 247 patients with suspected endophthalmitis underwent microbiological diagnostic work-up. All three culture methods were performed from 140 vitreous specimens. Vitreous fluid specimens were inoculated in blood culture bottles, aerobic and anaerobic broth solutions, and on solid media. Anti-infective susceptibility profiles were evaluated by semi-automated methods and/or gradient diffusion methods. Microorganisms were grown in 82 of 140 specimens for which all methods were performed (59%). Microorganisms were more frequently grown from blood culture bottles (55%) compared to broth solution (45%, p = 0.007) and solid media (33%, p < 0.0001). Considerable differences in the performance among culture media were detected for fungal pathogens. All grown fungi were detected by blood culture bottles (11 of 11, 100%). Broth solution recovered 64% and solid media 46% of grown fungi. No Gram-positive bacterium was resistant to vancomycin and all Gram-negative pathogens except for one isolate were susceptible to third-generation cephalosporins. In suspected endophthalmitis patients, blood culture bottles have a higher overall pathogen detection rate from vitreous fluid compared to conventional microbiological media, especially for fungi. The initial intravitreal antibiotic therapy with vancomycin plus third-generation cephalosporins appears to be an appropriate treatment approach for bacterial endophthalmitis.
... In a retrospective study, Melo et al reported that only 42% of all presumed endophthalmitis cases have had culture-positive results, and most of culture-positive cases were secondary to surgical procedures (62%). 40 In the current study, S. viridans was found to be the most frequent cause of postoperative endophthalmitis (37.5%) followed by S. epidermidis (21.9%) and Pseudomonas aeruginosa (12.5%) as the second and third most common organisms, respectively. ...
Background: Endophthalmitis is a severe and sight-threatening complication of ocular surgery or ocular trauma. The identification of common types and causative organisms is essential for prevention and management. Objective: The current study describes the prevalence of various types of endophthalmitis and the causative microbiological spectrum of each type treated in the Tertiary Referral Center in Iran. Methods: All cases of endophthalmitis admitted to the Emergency Department of Farabi Eye hospital (Tehran, Iran) between July 2013 and December 2014 were included in this study. The patients’ demographic data, type of endophthalmitis, aqueous or vitreous culture results, and treatment methods were recorded. Results: From 108 presumed endophthalmitis cases, post-operative endophthalmitis (68.5%) was the most frequent type followed by post-traumatic (25%), bleb-associated (4.6%), and endogenous (1.9%) types. Streptococcus viridians (37.5%) was the most common isolated organism in post-operative cases. In post-traumatic endophthalmitis patients, the most frequent causative organism was Staphylococcus epidermidis (70%). Conclusion: Many studies from other countries have reported that S. epidermidis is the leading cause of endophthalmitis after either intraocular surgeries or open-globe injuries, but the current study has shown that S. viridians is the most common isolated organism in post-operative endophthalmitis.
... Staphylococcus epidermidis an opportunistic pathogen and member of coagulase negative Staphylococci (CoNS) are normal inhabitant of human skin, mucosal and ocular surfaces and cause hospital acquired infections (Graham et al., 2007;Rogers et al., 2009;Le et al., 2014). This organism can cause number of ocular diseases like bacterial endophthalmitis conjunctivitis, blepharitis, and keratitis (Melo et al., 2011;Schimel et al., 2013;Bispo et al., 2014;Park et al., 2015). The predisposing risk factors associated with infections are mostly use of contact lenses, ocular surgery, and ocular inflammatory diseases (Bourcier et al., 2003;Keay et al., 2006;Park et al., 2015). ...
We examined the presence of virulence and antibiotic resistance genes, SCCmec types and determined the genomic diversity among ocular S. epidermidis isolates (patients-23, healthy controls-29). PCR determined the presence of antibiotic resistance genes, virulence genes and SCCmec types among all isolates. MLST and PFGE determined the genomic relatedness among them. All isolates of S. epidermidis showed resistance to at least one class of antibiotics of which 48 isolates were multidrug resistant and carried ARGs. Thirty-five isolates were methicillin resistant and carried mecA gene. Majority of the isolates were resistant to fluoroquinolones and showed mutation in gyrA, parC, and parE genes, however, few isolates showed additional novel mutations in parC gene. Of the MRSE strains, 17 strains carried SCCmec type IV, four type V, two type II, and two UT4. Seven strains carried novel combination of ccr complex and SCCmercury element, not reported earlier. All the S. epidermidis strains harbored icaA and icaD genes, 47 carried ACME operon, and 50 contained IS256. A noteworthy finding was the presence of ST179 among 43% of infected eye isolates an observation rarely reported among S. epidermidis. PFGE and MLST analysis showed genomic diversity among them. Statistical analysis suggests that few healthy conjunctiva isolates had characteristics similar to infected eye isolates. S. epidermidis strains carrying mecA gene are multidrug resistant, virulent and diverse irrespective of sources of isolation. IS256 cannot be used as marker to differentiate isolates of infected eye from healthy conjunctiva.
... Staphylococcus aureus is a significant cause of acute endophthalmitis, encountered most commonly following cataract surgery at a rate of 0.04 % [1,2]. S. aureus endophthalmitis can also follow trauma, intravitreal injections [3][4][5], other ocular surgeries, and septicemia [6,7]. S. aureus possesses virulence factors that give it the ability to adhere to and invade host tissues, combat the immune system, and resist a variety of antibiotics [8][9][10]. ...
PurposeTo compare the antibiotic susceptibilities and visual acuity (VA) outcomes in endophthalmitis caused by methicillin-resistant (MRSA) versus methicillin-sensitive S. aureus (MSSA). Methods
The records of 34 cases of S. aureus endophthalmitis at The New York Eye and Ear Infirmary from Jan 1997 to June 2011 were reviewed. Antibiotic susceptibility profiles over time and VA at presentation and at 3, 6, and ≥12 months were recorded. S. aureus isolates were grouped based on oxacillin resistance. ResultsOf the 34 cases, 15 (44 %) were MRSA and 19 (56 %) MSSA. Median presenting VA was hand motions (logMAR 4.0) in both the MRSA and MSSA groups. There was no statistically significant difference in VA between the MRSA and MSSA groups at 3, 6, or ≥12 months. No MRSA isolates were resistant to vancomycin or gentamicin. While over 85 % of MRSA isolates tested for fourth-generation fluoroquinolones were resistant, just 10 % MSSA isolates tested were resistant. There was a trend suggesting an increase in the proportion of MRSA isolates compared to MSSA isolates over the course of the study period. Conclusions
There was no statistical difference in short- or long-term VA outcomes between the MRSA and MSSA groups at any time point. Resistance to fourth-generation fluoroquinolones was present in over 85 % of MRSA isolates, but just 10 % of MSSA isolates. An increasing proportion of MRSA amongst S. aureus isolates was noted over the course of the study period.
... [14][15][16][17] However, cases of endophthalmitis due to fluoroquinolone-resistant isolates have begun to emerge. [18][19][20][21] Besifloxacin, a chlorinated fluoroquinolone, is the latestgeneration topical fluoroquinolone with broad-spectrum antibacterial activity, including activity against drug-resistant staphylococci, [22][23][24][25][26] comparable to that of vancomycin. 25,26 Besifloxacin was developed for ophthalmic use only and has been reported to have potent and balanced activity against DNA gyrase and topoisomerase IV. ...
The purpose of this study was to investigate the ocular bacterial flora in patients scheduled to undergo cataract surgery and compare the antibacterial effects of besifloxacin ophthalmic suspension 0.6% and moxifloxacin ophthalmic solution 0.5% in these patients.
This was a prospective, randomized, laboratory-masked clinical trial. Patients received besifloxacin or moxifloxacin "quater in die" or QID (four times a day) for 3 days before cataract surgery in the surgical eye and 1 hour before surgery in the nonsurgical fellow eye. Conjunctival and eyelid swabs were obtained from both eyes at baseline and after treatment, on the day of surgery (Visit 2). Swabs were processed for bacterial colony counts (in terms of colony-forming units) and species identification. In vitro antibiotic susceptibilities of isolates were determined using Clinical and Laboratory Standards Institute breakpoints.
Fifty-nine patients (n=28 besifloxacin, n=31 moxifloxacin) completed the study. The majority (73%) of conjunctival samples were culture negative at baseline. The most frequent isolates were coagulase-negative staphylococci (CoNS, 89%), specifically Staphylococcus epidermidis (72%). Both fluoroquinolones reduced the lid CFU values when administered QID for 3 days (P≤0.019), but only besifloxacin reduced the lid CFU estimate 1 hour following instillation of a single drop (P=0.039). Fewer besifloxacin-treated eyes had lids that were culture positive for CoNS at Visit 2 compared with moxifloxacin-treated eyes regardless of dosing regimen (P≤0.03). The minimum inhibitory concentration (MIC90) of besifloxacin against methicillin-resistant S. epidermidis (MRSE) was eightfold lower than that of moxifloxacin.
Besifloxacin appeared more effective in reducing bacterial counts on eyelids of patients undergoing cataract surgery, with significant reductions as early as 1 hour postdose, compared with moxifloxacin. Besifloxacin was more active in vitro against MRSE.
... The ability of commensal bacteria to form biofilms on the surface of IOLs prevents their clearance, and likely represents an important mechanism in the pathogenesis of post-cataract endophthalmitis. The occurrence of microbes in biofilms is consistent with the low rates of culture positivity for aqueous and vitreous samples [68]. ...
The ability to form biofilms in a variety of environments is a common trait of bacteria, and may represent one of the earliest defenses against predation. Biofilms are multicellular communities usually held together by a polymeric matrix, ranging from capsular material to cell lysate. In a structure that imposes diffusion limits, environmental microgradients arise to which individual bacteria adapt their physiologies, resulting in the gamut of physiological diversity. Additionally, the proximity of cells within the biofilm creates the opportunity for coordinated behaviors through cell-cell communication using diffusible signals, the most well documented being quorum sensing. Biofilms form on abiotic or biotic surfaces, and because of that are associated with a large proportion of human infections. Biofilm formation imposes a limitation on the uses and design of ocular devices, such as intraocular lenses, posterior contact lenses, scleral buckles, conjunctival plugs, lacrimal intubation devices and orbital implants. In the absence of abiotic materials, biofilms have been observed on the capsule, and in the corneal stroma. As the evidence for the involvement of microbial biofilms in many ocular infections has become compelling, developing new strategies to prevent their formation or to eradicate them at the site of infection, has become a priority.
... The spectrum and antibiotic susceptibility of organisms isolated from patients with endophthalmitis vary by region and country. Several reports have shown that all the Gram positive bacterial isolates are susceptible to vancomycin [8][9][10][11] except few cases of endophthalmitis with vancomycin resistant Enterococcus species [12,13]. Khera et al. from Hyderabad, India have shown that 1.5 % of the total Gram positive isolates are resistant to vancomycin [14]. ...
To review the susceptibility of bacterial isolates to ceftazidime and vancomycin isolated from patients with endophthalmitis. Microbiology records of patients with endophthalmitis between June 2010 and May 2013 were reviewed. Vitreous and AC fluids obtained from patients with endophthalmitis were subjected to direct microscopy examination and culture. Antibiotic susceptibility of the isolates was performed by Kirby Bauer disk diffusion method. Resistant to ceftazidime in Gram negative bacteria (GNB) by disk diffusion method is confirmed by minimum inhibitory concentration using E test. Culture was positive for bacteria/Fungi in 224/356 patients (62.9 %). Out of 224 patients, 191 (85.2 %) patients showed bacterial growth and 33 (14.0 %) showed fungal growth. Mixed bacterial infection was seen in five patients. Among the GNB, 23/123 (18 %) of the isolates were resistant to ceftazidime, and all the Gram positive bacteria 73/73 (100 %) were susceptible to vancomycin. Sixteen of 123 (13 %) GNB were resistant to amikacin. Although there is an increase in resistance to ceftazidime compared to amikacin in GNB, amikacin intravitreal injection is associated with macular toxicity and no single antibiotic has full coverage for all GNB. Combination of vancomycin and ceftazidime empiric therapy can be continued in patients with suspected endophthalmitis and treatment is modified based on clinical response and susceptibility results.
... Sequencing of culture-negative but PCR-positive samples allowed the identification of causative agent in seven patients, including a Proteus mirabilis, an uncommon but possible agent in postoperative endophthalmitis, 17 as well as a case of Moraxella spp., a Gram-negative bacteria with fastidious growth requirements. 26,27 However, the identification of causative organisms may be hindered by the presence of possible mixed infections, as it has been described in cases of acute or delayed endophthalmitis. 2,8 Mixed infection could also be suspected if exogenous or cross-contamination takes place. ...
Purpose:
Three different methods of DNA extraction from intraocular fluids were compared with subsequent detection for bacterial and fungal DNA by universal PCR amplification.
Material and methods:
Three DNA extraction methods, from aqueous and vitreous humors, were evaluated to compare their relative efficiency. Bacterial (Gram positive and negative) and fungal strains were used in this study: Escherichia coli, Staphylococcus epidermidis and Candida albicans. The quality, quantification, and detection limit for DNA extraction and PCR amplification were analyzed. Validation procedures for 13 aqueous humor and 14 vitreous samples, from 20 patients with clinically suspected endophthalmitis were carried out.
Results:
The column-based extraction method was the most time-effective, achieving DNA detection limits ≥10(2) and 10(3 )CFU/100 µL for bacteria and fungi, respectively. PCR amplification detected 100 fg, 1 pg and 10 pg of genomic DNA of E. coli, S. epidermidis and C. albicans respectively. PCR detected 90.0% of the causative agents from 27 intraocular samples collected from 20 patients with clinically suspected endophthalmitis, while standard microbiological techniques could detect only 60.0%. The most frequently found organisms were Streptococcus spp. in 38.9% (n = 7) of patients and Staphylococcus spp. found in 22.2% (n = 4).
Conclusions:
The column-based extraction method for very small inocula in small volume samples (50-100 µL) of aqueous and/or vitreous humors allowed PCR amplification in all samples with sufficient quality for subsequent sequencing and identification of the microorganism in the majority of them.
... The prognosis of streptococcal and Gram-negative B. cereus endophthalmitis is worse than coagulase-negative staphylococcal endophthalmitis. Also there has been increased resistance of coagulase-negative bacteria to fourth-generation quinolones [80] and hence systemic antibiotics should be tailored according to clinical needs and in consultation with local infection control team. There is high incidence of retinal detachment (17-58%) and risk of phthisis in eyes with post-traumatic endophthalmitis. ...
Management of ocular trauma is both challenging and controversial. Using current available evidence in literature and author experience this review aims to highlight critical issues in management of ocular and orbital trauma. This review provides a working framework from initial presentation, investigations, management principles, complications and prognosis to outcome and controversies involved in management. The review will focus on the concept of atraumatic repair of traumatized globe and will also give guidelines about strategic planning in ocular trauma management. Clinicians are occasionally faced with dilemmas and challenges in management of severely traumatized eyes with limited or no visual potential in view of life-time risk of sympathetic ophthalmia and the authors aim to address the controversy surrounding it.
... S taphylococcus epidermidis is the main colonizer of the human skin and wet mucosa, where it maintains a benign relationship with the host. Although found as a common constituent of the ocular surface microbiota (1), S. epidermidis is the leading cause of bacterial endophthalmitis following trauma and intraocular procedures (2,3) and has been frequently associated with infectious keratitis worldwide in patients with predisposing risk factors, including contact lens wear, trauma, surgery, and ocular surface inflammatory diseases (4,5). The success of S. epidermidis as a pathogen is particularly attributed to its capability to form agglomerations of cells embedded in and protected by an extracellular matrix composed of polysaccharides and/or proteins, known as biofilm, which confers resistance to antibiotic action and host immune defenses (6). ...
Staphylococcus epidermidis is an abundant member of the microbiota of the human skin and wet mucosa, which is commonly associated with sight-threatening infections in eyes with predisposing factors. Ocular S. epidermidis has become notorious because of its capability to form biofilms on different ocular devices and due to the evolving rates of antimicrobial resistance. In this study, the molecular epidemiology of 30 ocular methicillin-resistant S. epidermidis (MRSE) isolates was assessed using multilocus sequence typing (MLST). Antimicrobial resistance, accessory gene-regulator and staphylococcal cassette chromosome mec (SCCmec) types, biofilm formation and occurrence of biofilm-associated genes were correlated with MLST clonal complexes. Sequence types (STs) frequently found in the hospital setting were rarely found in our collection. Overall, 12 different STs were detected with a predominance of ST59 (30%), ST5 and ST6 (13.3% each). Most of the isolates (93.3%) belonged to the clonal complex 2 (CC2) and grouped mainly within subcluster CC2-II (92.9%). Isolates grouped within this subcluster were frequently biofilm producers (92.3%) with a higher occurrence of the aap (84.5%) and bhp (46.1%) genes compared to icaA (19.2%). SCCmec type IV (53.8%) was predominant within CC2-II strains, while 38.4% were nontypeable. In addition, CC2-II strains were frequently multidrug-resistant (80.7%) and demonstrated to be particularly resistant to ciprofloxacin (80.8%), ofloxacin (77%), azithromycin (61.5%) and gentamicin (57.7%). Our findings demonstrate the predominance of a particular MRSE cluster causing ocular infections, which was associated with high rates of antimicrobial resistance and particularly carriage of biofilm-related genes coding for proteinaceous factors implicated in biofilm accumulation.
... These findings are consistent with other studies. 35,36 Recently, these older generation broad spectrum antibiotics are regaining clinical interest due to their activity against wide range of multiple antibiotic resistant microorganisms. Their activity is assumed to be maintained due to low level use in the medical field. ...
Pharmaceutical manufacturing workers are exposed to significant amounts of product ingredients, including antibiotics. Such exposure could affect their nasal microflora.
To assess the effect of exposure to various unidentified pharmaceutical ingredients in cephalosporin-manufacturing and non-cephalosporin plants on the nasal carriage of Staphylococcus spp. and their antibiotic resistance.
Nasal swab samples were collected from 39 workers in both plants on three different occasions. Staphylococci were isolated and identified to genus level. Antibiotic resistance profiles were determined and subsequent identification to species level was performed.
There was complete absence of S. aureus in the samples collected from workers in both facilities. Multiple drug resistant coagulase-negative staphylococci (MDR CONS) prevalence rates were higher in the non-cephalosporin plant than in the cephalosporin plant, with resistance towards six classes of antibiotics. S. epidermidis was the prevalent species in the non-cephalosporin plant and S. haemolyticus prevailed in the cephalosporin-producing plant.
The observed prevalence of CONS in both production plants was the same. However, exposure to intermittent non-cephalosporin pharmaceuticals results in higher prevalence of MDR CONS compared to continuous exposure to cephalosporin.
Objective:
To identify characteristics and visual outcomes of coagulase-negative staphylococci (CoNS) endophthalmitis in the era after the Endophthalmitis Vitrectomy Study.
Design:
Single-centre retrospective analysis.
Participants:
Forty-two samples from 40 patients with documented CoNS endophthalmitis.
Methods:
Visual acuity outcomes of patients with CoNS endophthalmitis were assessed in relation to species and type of treatment instituted (e.g., pars plana vitrectomy [PPV] versus tap and injection of intravitreal antibiotics [T&I]). Strains were speciated using Gram and Giemsa staining and were further identified using API Staph and Biolog GEN III microplates. Genetic analysis was performed via polymerase chain reaction. Antibiotic susceptibility was assessed with disk diffusion.
Results:
Staphylococcus epidermidis was the most prevalent CoNS in our study. Cataract surgery and intravitreal injections were the most common sources for acute CoNS endophthalmitis. Eyes presenting with hand motion or better vision had similar mean final vision after either intravitreal antibiotics or PPV, whereas those with light perception or worse vision at onset had better outcomes after PPV only. Subanalysis showed that patients with S. epidermidis endophthalmitis (n = 39 eyes) had similar visual outcomes with either intravitreal injections or PPV regardless of visual acuity. Hypopyon and vitritis are not always present.
Conclusions:
Patients with S. epidermidis endophthalmitis may benefit similarly from either early vitrectomy or intravitreal antibiotic injections regardless of visual acuity. This finding complements the management standards set forth by the Endophthalmitis Vitrectomy Study.
In the world, microorganisms are the main cause of eye illnesses. Common bacterial infections of the eye, if untreated, can damage the eye's structures and lead to blindness and other visual impairments. The eye may get infected from the outside or as a result of bloodstream-borne germs invading the eye. Infectious bacteria can cause eye infections. Blepharitis, conjunctivitis, Listeriosis, keratitis, dacryocystitis, etc. are some of the frequent eye illnesses brought on by bacterial and fungal pathogens. The information on the variety of ocular surface microorganisms has been significantly increased by the series of genome-based methods through 16S rRNA gene-based identification. According to this research, a sufficient number of bacteria have a substantial part in the pathophysiology of eye illnesses, even though certain bacteria contribute to normal ocular processes. As a result, those with good vision can shed light on the intricacy of the ocular microflora and learn more about some visual requirements in addition to their vital contribution to the regular operation of the eye. Under these conditions, it is crucial to establish a quick, dependable, and affordable procedure that will eventually become a standard diagnostic process. In this literature review, many databases have searched, and the review has been methodically conducted to produce specific results for the hard eye infection disorders.
Case reports are detailed descriptions of unique clinical cases or short case series. They represent helpful first-hand source of evidence in clinical practice. The aim of this research was to perform a retrospective eight-year-period survey of a microbiology laboratory records, gathering microbiological and clinical patient information in orther to detect unusual patient-isolate-disease associations. Despite the common belief that infrequent pathogens are unlikely to be isolated in small cities like ours, we could recognize between the records reviewed a Salmonella urinary tract infection, a Bacteroides fragilis bacteriemia, a soft tissue infection with Mycobacterium tuberculosis in a lupic patient, a mycobacterioses caused by the recently described species Mycobacterium conceptionense and a postsurgical acute endophtalmitis outbreak caused by Streptococcus salivarius group. Working conditions that could facilitate or interfere unusual findings were identified as well. Finally, we concluded that case reports are invaluable tools in generating new hypothesis for future studies and clinical and epidemiological knowledge that can improve medical services as well as patients quality of life.
Postoperative endophthalmitis is a dreaded complication of intraocular surgery. Acute presentations need prompt management and good knowledge of differential diagnoses. In the last 10 years, progress in direct microbial detection and identification from intraocular samples included the use of blood culture systems and, more recently, matrix-assisted laser desorption ionization time-of-flight mass spectrometry, improving the rate of bacterial identification. Whatever the method used, diagnostic sensitivity is better for vitreous samples than for aqueous humor samples. Besides, molecular biology techniques have further improved the identification rate of infectious agents in intraocular samples. They also provide faster results compared to culture-based techniques. Quantitative real-time PCR (qPCR) can also determine the bacterial load in intraocular samples. Several studies have shown that intraocular bacterial loads in endophthalmitis patients are usually high, which helps differentiating infection from contamination. The prognostic value of qPCR remains to be validated. Whole genome DNA sequencing technologies facilitate direct and sequencing of single DNA molecules. They have the potential to increase the rate of microbiological identification. Some antibiotic resistance markers (e.g., methicillin resistance in staphylococci and vancomycin resistance in enterococci) may be detected earlier using molecular techniques (usually real-time PCR tests). Early determination of the involved microorganism and their antibiotic resistances can help establishing an earlier therapeutic strategy.
Purpose:
Methicillin-resistant Staphylococcus aureus (MRSA) is an opportunistic pathogen that can cause vision-threatening infections of the ocular surface, orbit, and periorbital structures. MRSA decolonization is a widespread technique employed outside of ophthalmology to reduce MRSA transmission and infection rates. Herein we explore whether decolonization protocols have a place in ophthalmology for combatting ocular MRSA infections.
Methods:
We conducted a focused review of the MRSA decolonization literature using PubMed and Cochrane databases to identify key studies in ophthalmology and the broader medical literature.
Results:
We summarize the relevance of the recent literature from an ophthalmic perspective, focusing on the clinical evidence supporting pre-operative MRSA decolonization. We also discuss current real-world decolonization practices, existing challenges, and propose recommendations for future opportunities to address these issues.
Conclusion:
Incorporating pre-operative MRSA decolonization approaches discussed herein may offer a new frontier for enhancing the ophthalmic care of patients colonized with MRSA.
The biofilm-forming potential of Staphylococcus aureus and Staphylococcus epidermidis, isolated from patients with Endophthalmitis, was monitored using glass cover slips and cadaveric corneas as substrata. Both the ocular fluid isolates exhibited biofilm-forming potential by the Congo red agar, Crystal violet and 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-(phenylamino) carbonyl-2H-tetra-zolium hydroxide (XTT) methods. Confocal microscopy demonstrated that the thickness of the biofilm increased from 4–120 h of biofilm formation. Scanning electron microscopic studies indicated that the biofilms grown on cover slips and ex vivo corneas of both the isolates go through an adhesion phase at 4 h followed by multilayer clumping of cells with intercellular connections and copious amounts of extracellular polymeric substance. Clumps subsequently formed columns and eventually single cells were visible indicative of dispersal phase. Biofilm formation was more rapid when the cornea was used as a substratum. In the biofilms grown on corneas, clumping of cells, formation of 3D structures and final appearance of single cells indicative of dispersal phase occurred by 48 h compared to 96–120 h when biofilms were grown on cover slips. In the biofilm phase, both were several-fold more resistant to antibiotics compared to planktonic cells. This is the first study on biofilm forming potential of ocular fluid S. aureus and S. epidermidis on cadaveric cornea, from attachment to dispersal phase of biofilm formation.
We describe a case of endogenous endophthalmitis in an elderly man caused by Streptococcus salivarius . An 88-year-old male patient with diabetes with iron deficiency anaemia and history of transcatheter aortic valve implantation presented with an insidious clinical picture of atraumatic endophthalmitis. No internal or external source could be identified. Diagnostic and therapeutic vitrectomy revealed papillomacular abscess and vitreous fluids grew S. salivarius . Despite lack of an identifiable source of infection, a high index of suspicion for atypical presentations is required in patients with multiple comorbidities that could weaken their immune system towards opportunistic infections. Early detection, microbiological evaluation and prompt treatment are critical to avoid disastrous outcomes. While S. salivarius has been implicated in cases of exogenous endophthalmitis, this is the first reported case of endogenous endophthalmitis due to S. salivarius .
Purpose
To review the incidence, aetiology and outcomes of endophthalmitis during a 20‐year period in a Norwegian university hospital.
Methods
Single‐centre retrospective review. Medical records of all patients admitted to Stavanger University Hospital with suspected endophthalmitis between January 1999 and December 2018 were reviewed.
Results
We identified 84 eyes of 81 patients. Postoperative endophthalmitis (PE) was seen in 64 eyes (76%), endogenous endophthalmitis in thirteen eyes (15%), trauma in four eyes (5%) and three eyes (4%) had keratitis‐associated endophthalmitis. Administration of intravitreal injections (IVI) was the most common cause (30%), followed by cataract surgery (CS) (21%). Of 40238 IVI, 23 PE cases were identified (incidence, 0.057%; 95% confidence interval [CI] 0.036–0.086%). Of 39697 CS, 12 PE cases were identified (incidence, 0.030%; 95%CI 0.016–0.053%). After introduction of intracameral cefuroxime PE incidence after CS decreased from 0.10% in 1999–2003 to 0.015% in 2004–2018 (p = 0.003). Eighty‐four per cent of organisms were Gram‐positive. Coagulase‐negative staphylococci accounted for 54% of culture‐proven cases, and 89% of post‐IVI culture‐proven cases. Thirty eyes (36%) either regained their previous vision or lost ≤1 Early Treatment Diabetic Retinopathy Study line. One third of endophthalmitis cases had a favourable visual outcome of logMAR 0.2 or better.
Conclusion
PE after IVI occurred in 1 in 1750 procedures, and was the most common cause of PE. The incidence of PE after CS has decreased >sixfold since 2003, to 1 in 6700 surgeries. A high proportion of low‐virulence bacterial species may have contributed to the favourable visual outcome.
Purpose: To evaluate the performance and speed of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) when identifying the pathogenic microorganism of endophthalmitis compared to conventional microbiological culturing.
Methods: Forty-four patients with suspected endophthalmitis who had undergone vitrectomy were enrolled. Vitreous specimen was analyzed using either conventional culturing or MALDI-TOF MS.
Results: The identification rates of the conventional microbiological culture and MALDI-TOF MS were 45.5% (20/44) and 65.9% (29/44), respectively (Kappa value 0.787, P < 0.000). The mean detection times by the standard culturing method and MALDI-TOF MS were 5.39 ± 0.56d and 3.17 ± 0.40d (P < 0.001). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MALDI-TOF MS were 70.59%, 54.17%, 80.00%, and 86.67%, respectively. Polymicrobial endophthalmitis was identified in 6.82% of the patients (3/44) using conventional microbiological culturing. However, MALDI-TOF MS failed to identify any polymicrobial infection.
Conclusions: With a higher sensitivity, acceptable specificity and a shorter detection time, MALDI-TOF MS was an efficient technique for the rapid identification of a pathogenic microorganism in endophthalmitis.
Early diagnosis and treatment of endophthalmitis will optimise visual prognosis. Blood culture sensitivities should tailor antibiotic choice.
Staphylococcus aureus is an important human bacterial pathogen responsible for a wide variety of ocular diseases, including sight-threatening infections such as keratitis, corneal flap melt after laser-assisted in situ keratomileusis (LASIK), cellulitis, endophthalmitis, and panophthalmitis. Staphylococcus aureus isolates that are resistant to methicillin are known as methicillin-resistant Staphylococcus aureus (MRSA) and are usually also resistant to other β-lactam antimicrobial drugs. In current practice, methicillin sensitivity is usually performed with oxacillin or cefoxitin, as methicillin is no longer commercially available in the United States. Oxacillin is more likely to maintain its activity during storage better than methicillin, while cefoxitin can give more reproducible and accurate results than tests with oxacillin or methicillin. The organisms are still called “MRSA” and not “oxacillin-resistant Staphylococcus aureus” or “cefoxitin-resistant Staphylococcus aureus” because of this historic role.
Prevention and elimination of endophthalmitis are a constant goal of every ophthalmic surgeon. Today virtually every surgeon follows a standard of care that involves antisepsis and antibiotics without knowing exactly the reason (why), the modality (how), and the precise time (when) to intervene with effective prophylactic measures [1]. The introduction of various antimicrobials for treating a variety of infections was the reason for performing antimicrobial susceptibility testing as a routine procedure in all microbiology laboratories. Pharmacokinetics and spectrum of activity of antimicrobial intravitreal drugs are an important consideration. Dose, pH, ionization, protein binding, and route of entry also affect the drug concentration. Ocular factors such as the surgical status of the eye, the presence or absence of lens and vitreous, and degree of breakdown of the blood retinal barrier are the host factors to consider [2]. The microbial spectra and susceptibility patterns have exhibited variations over time and differ according to geographic location, population, and ethnic groups. Because of the rapidly progressive nature of endophthalmitis, it is important to monitor the microbial spectra and antibiotic susceptibilities at the local level through periodic analyses to ensure that empirical therapy remains appropriate [1]. The results of in vitro antibiotic susceptibility testing guide clinicians in an appropriate selection of initial empiric regimens and the drugs used for individual patients in specific situations. The selection of an antibiotic panel for susceptibility testing is based on the commonly observed susceptibility patterns and is revised periodically. In the present chapter, we have reviewed the global trends in the last few decades in the changes in antibiotic susceptibility patterns for bacteria and fungi causing endophthalmitis.
Purpose:
The host immune reaction during endophthalmitis, studied in particular through the intraocular cytokine network, is essential for the comprehension of the disease and the development of new therapies. Therefore, the purpose of this study was to elucidate the cytokine composition of aqueous humor during endophthalmitis.
Methods:
In a multicenter case-control study, forty-nine patients with postoperative endophthalmitis and 60 controls (cataract surgery) were included. Visual acuity, local inflammatory grading, medical history and intraocular levels of 27 cytokines and chemokines (measured by multiplex immunoassay) were recorded.
Results:
During endophtalmitis, an increase in total cytokines was observed. The raise of Th1 cytokines was particularly noticeable. Chemokines, such as IL-8, MIP-1 β, MCP-1, G-CSF and IP-10, also increased. Pearson's correlation analyses showed a poor visual prognosis with high levels of IL-8, MCP-1 and VEGF and a low level of IL-10 at admission.
Conclusion:
An increase in inflammatory cytokines is noticeable during endophthalmitis, with a particular emphasis on IL-8, MCP-1 and VEGF. Targeted anti-inflammatory and anti-VEGF treatments may be of interest in the future.
Endophthalmitis is a severe eye infection that may result in permanent loss of useful vision in the affected eye. Most cases are exogenous and occur as a complication of cataract surgery, an intravitreal injection, or penetrating ocular trauma. Endogenous endophthalmitis results from hematogenous seeding of the eye by bacteria or fungi, but bacteremia or fungemia may be transient and patients may present without symptoms of systemic infection. Nearly all endophthalmitis patients present with decreased vision, and some also have eye pain. Eye examination usually reveals a hypopyon and intraocular inflammation. Diagnosis is clinical, supported by cultures of the vitreous and/or aqueous or by blood cultures in some endogenous cases. Molecular diagnostic techniques have been used in research laboratories for pathogen identification in endophthalmitis and offer the possibility of rapid diagnosis, including in culture-negative cases. Intravitreal injection of antibiotics is the most important component of treatment; some cases also benefit from surgical debridement of the vitreous by a vitrectomy. The visual outcome depends partly on the pathogen: coagulase-negative staphylococcal endophthalmitis has a better prognosis than does streptococcal endophthalmitis, for example. Endophthalmitis is a medical emergency, and prompt diagnosis and treatment are essential for saving vision.
Endophthalmitis is a potentially devastating eye infection involving the vitreous and/or aqueous. In most patients, endophthalmitis results in some degree of irreversible vision loss in the affected eye; in some patients, all useful vision in that eye is lost. The term “endophthalmitis” is nearly always used to describe intraocular infection due to bacteria or fungi, while cases of intraocular inflammation due to viruses, parasites, and noninfectious etiologies are usually considered types of uveitis.
Endophthalmitis cases may be classified by etiology into categories such as postoperative, post-intravitreal injection, post-traumatic, bleb-related, keratitis-related, or endogenous. The clinical features and microbiology vary by category, and the relative frequency of these categories varies worldwide. This chapter provides an overview of endophthalmitis as seen around the world, and summarizes our current understanding of the pathogenesis, clinical presentation, microbiology, diagnostic methods, treatment options, and visual outcomes of endophthalmitis.
Resistance to antimicrobial agents used to treat human infections is a major public health threat that results from the broad use of antibiotics in medicine, veterinary care, and agriculture. Exposure to antibiotics promotes the selection of successful resistant bacterial lineages possessing molecular mechanisms that lead to variable levels of resistance. Increasing use of antibiotics for treatment and prophylaxis of eye infections has resulted in the emergence of resistant ocular organisms. The use of topical antibiotics for prophylaxis of postoperative endophthalmitis, especially fluoroquinolones, has paralleled the recent increase in the number of patients undergoing intraocular procedures. This has resulted in the upsurge of antibiotic-resistant organisms colonizing the ocular microbiota and also as significant causes of postoperative infections. Contemporary ocular staphylococci isolates, the leading causes of bacterial endophthalmitis, are becoming increasingly resistant to the most commonly used topical fluoroquinolone agents. Despite the widespread use of these agents for prophylaxis, current evidence does not support the efficacy of topical fluoroquinolones in preventing endophthalmitis, but does support an association with their use and the selection of spontaneous resistant mutants in the ocular surface microbiota. Studies of pharmacokinetics and pharmacodynamics have demonstrated that due to reduced penetration in association with increasing levels of resistance, none of the currently used topical fluoroquinolones are likely to be effective in eliminating staphylococci isolates in the anterior chamber. This highlights the need for prospective randomized studies to evaluate whether or not these topical antibiotics are really needed for preventing postoperative or post-injection endophthalmitis. The development of new strategies to increase regimens or delivery mechanisms that would optimize the intraocular concentration of antibiotics may help prevent the selection and spread of resistant mutants and improve clinical effectiveness.
Microbiological diagnosis in endophthalmitis is evolving. Stains and cultures remain the “gold standard” for laboratory diagnosis and confirmation; however, the role of the laboratory is being redefined and expanded to meet the demand for increased sensitivity and quicker turnaround times. The demand for quicker turnaround times and increased diagnostic sensitivity is fueled and paralleled by the increase in the number of patients at risk.
New culture-dependent and culture-independent procedures are slowly being integrated into clinical microbiology laboratories to help meet this need. Incorporating these new tests to complement traditional method will result in improved diagnostics and increased benefit for patient care and positive outcomes.
Purpose:
To review antibiotic resistance associated with S. aureus endophthalmitis and the virulence of S. aureus.
Methods:
Review of the current and prospective approaches for treating S. aureus endophthalmitis.
Results:
Bacterial endophthalmitis remains to be a major threat for vision. S. aureus endophthalmitis specifically, carries a poor visual prognosis making early diagnosis and treatment crucial. Methicillin resistant Staphylococcus aureus (MRSA) endophthalmitis represents a significant number of S. aureus endophthalmitis cases. MRSA with reduced susceptibility to glycopeptide antibiotics such as vancomycin (vancomycin intermediate S. aureus, VISA) have also emerged in the ocular infections, and there has been a rise in S. aureus resistance to new and old generation fluoroquinolones that are commonly used for prophylaxis after intravitreal injections and intraocular surgeries.
Conclusions:
With the rise in the number of penetrating procedures in the ophthalmology practice and the parallel rise in antibiotic resistance, prophylaxis and awareness of the antimicrobial resistance profiles remain crucial and the identification of novel antimicrobials is essential.
Molecular analysis of ocular fluids and biopsies has taken a prominent position in the diagnosis of ocular infections. Currently real-time PCR is the mostly applied assay worldwide. In particular for viruses and fastidious microorganisms, PCR has replaced culture since PCR is faster and more sensitive. PCR has been used for the diagnosis of trachoma, herpes virus keratitis, and infectious uveitis for a long time and is not only applied for the detection of the infectious agent but also to monitor the effect of treatment. The application of molecular tools for the diagnosis of bacterial and fungal keratitis and endophthalmitis is taking a flight. Panbacterial and panfungal PCR assays not only allow for fast detection of a microorganism but can be combined with subsequent species and strain identification and antibiotic resistance profiling. However, most current molecular tools are expensive and require costly well-equipped laboratories. Therefore, inexpensive and point-of-care molecular detection assays are being developed. PCR analysis and other molecular diagnostic tools have their limitations. False-negative results may occur due to the absence of the infectious agent in the analyzed sample which may be related to the type of sample analyzed, to the time of sampling in the course of disease, or merely to the nature of the ocular infection. False-positive outcomes may occur due to contamination or bystander effects, resulting from the ever-increasing sensitivities of the molecular assays. When using molecular diagnostic tools, one should be aware of their limitations and consider other diagnostic tools as well.
To report a case of a rapidly progressive endogenous endophthalmitis with subretinal abscess that involved the macula and was treated with early vitrectomy.
To study the prevalence of methicillin-resistant Staphylococcus aureus among S. aureus ocular infections in a tertiary health center in Brazil and compare antibiotic susceptibility patterns between MRSA and methicillin-susceptible S. aureus isolates.
Electronic records from the ocular microbiology laboratory of the Universidade Federal de São Paulo were retrospectively reviewed. During a 10-year period (between January 2000 and December 2009) all conjunctivitis, keratitis, and endophthalmitis cases with a positive culture for S. aureus were identified. Antibiotic susceptibility was determined using the Kirby-Bauer disk diffusion method.
Five hundred sixty-six S. aureus isolates were identified; of those, 56 (9.9%) were resistant to methicillin. Throughout the 10-year period, Staphylococcus aureus showed a significant increasing trend from 7.55% to 16.18% among overall S. aurues infections (p=0.001) and from 3.7% to 13.16% in conjunctivitis (p=0.001). Conversely, we did not observe the same trend among those with keratitis (p=0.38). Staphylococcus aureus isolates showed higher resistance rates to tobramycin, gentamicin, ciprofloxacin, gatifloxacin, and moxifloxacin when compared with S. aureus isolates (p< 0.001). All cases were susceptible to vancomycin.
We observed an increasing trend in the overall prevalence of Staphylococcus aureus ocular infections and statistically significant higher resistance rates to commonly used antibiotics compared to Staphylococcus aureus. Our data supports the need for constant bacterial surveillance and should be taken into consideration before initiating empiric treatment of ocular infections.
Staphylococcus epidermidis is considered a commensal bacterium; however, it is frequently isolated from ocular infections showing a multidrug resistance. Ciprofloxacin-resistant strains have been isolated from ocular infections; however, resistance to quinolone, such as gatifloxacin and moxifloxacin, is not often studied, consequently the resistance mechanism is unknown. Our aim was to address the quinolone resistance and to explore the resistance mechanism in S. epidermidis strains isolated from ocular infections.
S. epidermidis strains were isolated from patients with conjunctivitis (n = 23), endophthalmitis (n = 14) and corneal ulcers (n = 7). Minimum inhibition concentrations were determined by broth and agar dilution methods for moxifloxacin, gatifloxacin, balofloxacin, rufloxacin and pazufloxacin. Mutations were identified by sequencing the gyrA and parC genes, and their expression was determined by reverse transcriptase polymerase chain reaction.
We found that 13.6% (6/44) of the strains were quinolone resistant. In endophthalmitis, 21.4% were gatifloxacin, moxifloxacin and balofloxacin resistant. In corneal ulcers, 14.2, 14.2 and 28.5% were gatifloxacin, moxifloxacin and balofloxacin resistant, respectively, and in conjunctivitis only 4.3% were gatifloxacin resistant. The 6 strains with quinolone resistance showed mutations at Ser84Phe for the gyrA gene, and Ser80Phe for the parC gene. Gatifloxacin did not change the expression levels of gyrA and parC genes.
S. epidermidis strains isolated from three ocular pathologies were gatifloxacin and moxifloxacin resistant due to mutations on the gyrA and parC genes.
Diagnosis of bacterial endophthalmitis (BE) often fails due to: (1) insufficient volumes of vitreous fluid (VF) and aqueous humour (AH); (2) lack of sensitivity of culture; (3) antibiotic treatments; (4) polymerase chain reaction (PCR) cross-contamination; and (5) limitations on the interpretation of the real-time PCR melting curve. We developed a fast real-time (f-real-t) PCR to improve the performance of the laboratory diagnosis of BE.
The following samples were processed after adding an internal control: phosphate buffered saline (PBS); VF, AH and cell suspensions spiked with Bacteria (Bac); VF and AH from patients with endophthalmitis; and VF and AH from non-infective patients. DNA was extracted (MagNA Pure) and added to four tubes containing selected primers and probes for the identification and quantification of all Bac and eight genera by f-real-t PCR. Diagnostic performances based on direct microscopic examination, culture and f-real-t PCR were compared.
The f-real-t PCR detected at least 0.01 colony-forming units (CFU) of Bac/microl with no cross-reactivity with fungi. Correlation with culture-positive results was 100%. Sixty per cent of BE samples tested culture-positive, but f-real-t PCR tested positive for 90%. Samples from non-infective cases were negative.
The f-real-t PCR detected and quantified Bac, Staphylococci, Streptococci, Haemophilus, Pseudomonas, Enterobacteria, Acinetobacter, Propionibacteriacae and Corynebacteria in one run. Cultures required several hours to days (with a non-negligible number of false-negative results) and the f-real-t PCR was completed in 90 min. The f-real-t PCR is presented as a new tool for the diagnosis of BE: its usefulness requires validation with larger series of samples.
To assess the distribution of microorganisms isolated from patients with bacterial endophthalmitis and their antimicrobial susceptibility.
Retrospective analysis of medical and microbiological records of patients with suspected diagnosis of endophthalmitis and bacterial culture-proven at the Department of Ophthalmology, UNIFESP, between January 1 2000 and December 31 2005.
153 (33.9%) of 451 patients showed positive bacterial culture. A total of 155 microorganisms were isolated, 79.35% were gram-positive and 20.65% gram-negative. Staphylococcus (CoNS) (41.94%) were the most frequently isolated. The antimicrobial susceptibility for gram-negative microorganisms was as follows: amikacin 87.10%, tobramycin 80.65%, ciprofloxacin 96.67%, levofloxacin, gatifloxacin and moxifloxacin 100%, ceftazidime 85.0%, and gentamicin 80.65%. Vancomycin sensitivity among gram-positive microorganisms was 100%. S. aureus and CoNS showed 83.33% of susceptibility to oxacillin, 89.61% to ciprofloxacin and 100% to gatifloxacin and moxifloxacin. The main acquisition mechanism was postoperative (60.65%).
We detected a low sensitivity of vitreous/aqueous culture for the etiologic diagnosis of endophthalmitis. The empiric antimicrobial therapy or prophylaxis should be active against gram-positive bacteria, particularly staphylococci. Surveillance studies of bacterial resistance are important for a better utilization of antimicrobials in this clinical setting.
Endophthalmitis is a severe inflammation of the interior of the eye caused by the introduction of contaminating microorganisms following trauma, surgery, or hematogenous spread from a distant infection site. Despite appropriate therapeutic intervention, bacterial endophthalmitis frequently results in visual loss, if not loss of the eye itself. Although the pathogenicity of bacterial endophthalmitis has historically been linked with toxin production during infection, a paucity of information exists as to the exact mechanisms of retinal toxicity and the triggers for induction of the intraocular immune response. Recently, research has begun to examine the bacterial and host molecular and cellular events that contribute to ocular damage during endophthalmitis. This review focuses on the causative agents and therapeutic challenges of bacterial endophthalmitis and provides current data from the analysis of the role of bacterial virulence factors and host inflammatory interactions in the pathogenesis of eye infections. Based on these and related studies, a hypothetical model for the molecular pathogenesis of bacterial endophthalmitis is proposed. Identifying and understanding the basic mechanisms of these bacterium-host interactions will provide the foundation for which novel, information-based therapeutic agents are developed in order to prevent vision loss during endophthalmitis.
PURPOSE: To determine the antibiotic susceptibility of preoperative conjunctival bacterial flora. DESIGN: In vitro study. METHODS: Antibiotic susceptibility of conjunctival bacterial strains isolated from 164 patients undergoing intraocular surgery was determined using the Kirby-Bauer disk,diffusion technique. RESULTS: Among the 162 bacteria isolated, 124 (76%) were coagulase,negative staphylococci (CNS), with 2% resistant to gatifloxacin and moxifloxacin, and none were resistant to vancomycin or minocycline. Other bacteria isolated were 19 Staphylococcus aureus (S. aureus), 8 Streptococcus Group D, and 11 gram negative rods. Most S. aureus (> 85%) were susceptible to all antibiotics except for the penicillin and macrolide groups. No streptococci were resistant to gatifloxacin, levofloxacin, moxifloxacin, mezlocillin, imipenem, or vancomycin. None of the gram,negative rods were resistant to the fluoroquinolones. Approximately one half of all bacteria were resistant to erythromycin. One in three patients harbored multi-resistant bacteria (resistant to >= five antibiotics). CONCLUSIONS: Newer-generation fluoroquinolones provide excellent broad-spectrum coverage against conjunctival bacterial flora. (c) 2005 by Elsevier Inc. All rights reserved.
PURPOSE: To present the microbial spectrum and susceptibilities of isolates in postoperative endophthalmitis.
To compare the susceptibility and efficacy of 3 fluoroquinolones, (levofloxacin, gatifloxacin, and moxifloxacin) in treating conjunctival bacteria in patients having ocular surgery.
Osaka University Hospital, Osaka, and Tohoku University Hospital, Miyagi, Japan.
Eyes of patients were examined preoperatively. Aerobic and anaerobic cultures were obtained from conjunctival swabs. The minimum inhibitory concentrations (MICs) of levofloxacin, gatifloxacin, and moxifloxacin for isolated strains were determined. Using the MIC values, descriptive statistics (median, MIC(50), MIC(90), mode, and range), susceptibility, and efficacy of each fluoroquinolone were calculated for the bacteria isolated, and the data were analyzed statistically.
Of the 200 eyes sampled, 163 (81.5%) had positive bacterial growth. From the 163 eyes, 235 bacterial strains were isolated: 116 (49.4%) Propionibacterium acnes; 58 (24.7%) coagulase-negative Staphylococcus (CNS), including 36 methicillin-sensitive CNS (MS-CNS) and 22 methicillin-resistant CNS (MR-CNS); 10 (4.3%) Staphylococcus aureus, including 6 methicillin-sensitive S aureus and 4 methicillin-resistant S aureus (MRSA); and 29 (12.3%) Corynebacterium. Approximately 40% of Staphylococci (22/58 CNS, 37.9%; 4/10 S aureus, 40.0%) were methicillin-resistant. Furthermore, 18 (81.8%) of MR-CNS and all 4 MRSA were fluoroquinolone resistant. The MICs of moxifloxacin and gatifloxacin were statistically significantly lower than those of levofloxacin for CNS and P acnes (P<.05, Kruskal-Wallis test). However, there was no statistically significant difference in the susceptibility patterns of the fluoroquinolones for these strains (P>.05, McNemar test).
Because many methicillin-resistant and fluoroquinolone-resistant strains were isolated from the conjunctiva preoperatively, clinicians should be mindful of endophthalmitis or ocular infections associated with these strains.
To determine the microbiologic spectrum and antibiotic susceptibilities of infecting organisms in postoperative endophthalmitis and to evaluate the effects of operative factors on the microbiologic spectrum.
Patients with bacterial endophthalmitis presenting within six weeks of cataract extraction or secondary intraocular lens implantation (IOL) were evaluated. Cultures and Gram stains were performed on intraocular specimens and susceptibility tests on the isolates.
Confirmed microbiologic growth was demonstrated from intraocular specimens from 291 of 420 patients (69.3%). Gram-positive bacteria were isolated from 274 patients (94.2%) with confirmed growth and gram-negative bacteria from 19 (6.5%). Two hundred twenty-six of the 323 isolates obtained (70.0%) were gram-positive, coagulase-negative micrococci, 32 (9.9%) Staphylococcus aureus, 29 (9.0%) Streptococcus species, seven (2.2%) Enterococcus species, ten (3.1%) miscellaneous gram-positive species, and 19 (5.9%) gram-negative species. All gram-positive isolates tested were susceptible to vancomycin. Seventeen gram-negative isolates (89%) were susceptible to both amikacin and ceftazidime and two (11%) were resistant to both. Anterior chamber or secondary IOL implantations were associated with higher rates of infection with gram-positives other than coagulase-negative micrococci than were posterior chamber IOL implantations (P = .022) or primary cataract extractions (P = .024).
Gram-positive, coagulase-negative micrococci predominated in this series. Vancomycin was active against all gram-positive isolates tested. Amikacin and ceftazidime showed equivalent activity against gram-negative isolates. Secondary or anterior chamber lens implantations were associated with a possible spectrum shift toward gram-positive organisms other than the coagulase-negative micrococci.
Endophthalmitis is an inflammatory reaction of intraocular fluids or tissues. Infectious endophthalmitis is one of the most serious complications of ophthalmic surgery. Occasionally, infectious endophthalmitis is the presenting feature of an underlying systemic infection. Successful management of infectious endophthalmitis depends on timely diagnosis and institution of appropriate therapy. Recognition of the different clinical settings in which endophthalmitis occurs and awareness of the highly variable presentation it may have facilitate timely diagnosis. Biopsy of intraocular fluid/tissue is the only method that permits reliable diagnosis and treatment. The different presenting clinical settings, a rational approach to diagnosis (i.e., when, what, and how to biopsy), and the treatment of infectious endophthalmitis are reviewed.
Endophthalmitis following penetrating eye injuries has a relatively poor prognosis due to the underlying eye trauma and the frequency of more virulent organisms such as Bacillus species. Risk factors for infection include 1) retained intraocular foreign body, 2) a rural injury setting, 3) delay in primary wound closure, and 4) disruption of the crystalline lens. Although endophthalmitis is difficult to distinguish from traumatic changes, recognition of early clinical signs of endophthalmitis, such as hypopyon, vitritis, or retinal periphlebitis, is important and early treatment is recommended. Comprehensive prophylactic antibiotic treatment at the time of injury repair combined with timely diagnostic vitrectomy and injection of intravitreal antibiotics when infection is suspected may significantly improve visual acuity outcomes following penetrating injuries. Treatment includes intravitreal, periocular, and systemic antibiotics. Intravitreal and periocular corticosteroids are also recommended. Recent and past literature supporting these recommendations, as well as the authors' specific prevention and treatment protocols for post-traumatic endophthalmitis, is included in this review.
To present the microbial spectrum and susceptibilities of isolates in posttraumatic endophthalmitis.
Isolates from 182 eyes of 182 patients who underwent vitrectomy for posttraumatic endophthalmitis were examined.
One hundred thirteen (62.1%) of 182 vitreous samples were culture-positive, and 23 (20.4%) of 113 culture-positive cases were polymicrobial, including three (2.7%) trimicrobial cases, yielding a total of 139 isolates. Isolates included 63 (45.3%) gram-positive cocci, 24 (17.3%) gram-positive bacilli, 25 (18.0%) gram-negative organisms, seven (5.0%) Actinomycetes-related organisms, and 20 (14.4%) fungi. Susceptibilities to amikacin, ceftazidime, chloramphenicol, cefazolin, ciprofloxacin, gentamicin, and vancomycin are reported.
This study represents a large series on microbial spectrum and susceptibilities in posttraumatic endophthalmitis. We report a high prevalence of gram-positive bacilli species and polymicrobial infections containing gram-negative species, underscoring the importance of broad-spectrum, combination antibiotics in the empiric treatment of posttraumatic endophthalmitis.
To assess the usefulness of polymerase chain reaction (PCR) in detection of bacteria in ocular samples.
Thirty-seven samples (aqueous and vitreous) were collected from 25 eyes showing typical symptoms and clinical signs of bacterial endophthalmitis. Ocular samples were also collected from 38 eyes that underwent routine surgery and from 15 eyes with intraocular inflammation due to nonbacterial causes. Panbacterial PCR was performed with a nested pair of 16S rRNA gene primers. Subsequent bacterial identification was completed for 18 paired samples (nine eyes) using restriction fragment length polymorphism (RFLP) and DNA sequencing.
A 100% concordance was obtained between PCR and culture-positive samples. A PCR product was amplified from all 37 intraocular samples from eyes with suspected infection, whereas only 15 of 22 vitreous samples and 5 of 15 aqueous samples were culture positive. Culture-negative PCR-positive samples contained a preponderance of gram-negative bacterial sequences. Cloning and DNA analysis revealed 30 DNA sequences and included eight bacterial 16S rDNA, which currently remain unidentifiable. The presence of bacterial DNA was associated with an inflammatory response suggestive of infection and not colonization. All 15 samples from inflamed eyes with diverse uveitis diagnoses were PCR negative. The false-positive rate, due to contamination during sampling, was 5%.
Bacterial DNA was detected in all patients with typical clinical signs of endophthalmitis. Gram-negative organisms seem to play a much more important role in the pathogenesis of this disease than previously thought. PCR-based techniques have great value in the confirmation of the diagnosis of bacterial endophthalmitis especially in culture-negative eyes.
In eyes with suspected endophthalmitis, early diagnosis and appropriate treatment have been noted to be associated with a better visual outcome. Currently, however, confirmation of the diagnosis of endophthalmitis (bacterial and/or fungal) is dependent on conventional techniques of microbiological isolation of organisms which require between one and twelve days. Furthermore, many samples prove to be culture-negative. In order to improve the rate of microbiological diagnosis, PCR technology has been successfully applied to the detection of bacteria and fungi in ocular samples. Specific oligonucleotide primers have been used to detect the presence of pathogens, which have been subsequently identified using RFLP analysis, DNA sequencing, and/or cloning techniques. Results demonstrated that PCR-based methods are rapidly able to confirm the presence of pathogens with high specificity and sensitivity. PCR-based techniques have also been used to rule out with confidence the presence of pathogens, a unique advantage of this methodology. The use of molecular methods has significantly increased the number of intraocular samples from which a confirmed diagnosis is made and reduced the time to laboratory diagnosis. PCR-based methods promise to be useful diagnostic tools in the management of these patients, especially those from whom ocular samples prove to be culture-negative.
To determine the antibiotic susceptibility of preoperative conjunctival bacterial flora.
In vitro study.
Antibiotic susceptibility of conjunctival bacterial strains isolated from 164 patients undergoing intraocular surgery was determined using the Kirby-Bauer disk-diffusion technique.
Among the 162 bacteria isolated, 124 (76%) were coagulase-negative staphylococci (CNS), with 2% resistant to gatifloxacin and moxifloxacin, and none were resistant to vancomycin or minocycline. Other bacteria isolated were 19 Staphylococcus aureus (S. aureus), 8 Streptococcus Group D, and 11 gram-negative rods. Most S. aureus (>85%) were susceptible to all antibiotics except for the penicillin and macrolide groups. No streptococci were resistant to gatifloxacin, levofloxacin, moxifloxacin, mezlocillin, imipenem, or vancomycin. None of the gram-negative rods were resistant to the fluoroquinolones. Approximately one half of all bacteria were resistant to erythromycin. One in three patients harbored multi-resistant bacteria (resistant to > or = five antibiotics).
Newer-generation fluoroquinolones provide excellent broad-spectrum coverage against conjunctival bacterial flora.
To determine the reported incidence of acute endophthalmitis following cataract extraction over time and to explore possible contributing factors, such as type of cataract incision.
A systematic review of English-language articles was conducted by performing a broad search of PubMed from 1963 through March 2003 using such terms as cataract extraction, endophthalmitis, and postoperative complication. Additional studies were identified from bibliographies of relevant articles and published proceedings. Surgical approach was recorded, when available. Pooled incidence rates and relative risks of developing endophthalmitis using different incision techniques were assessed.
From 4916 unique, potentially relevant citations, 215 studies that addressed endophthalmitis and met the selection criteria were analyzed. A total of 3 140 650 cataract extractions were pooled resulting in an overall rate of 0.128% of postcataract endophthalmitis. However, the incidence of acute endophthalmitis changed over time, with a significant increase since 2000 compared with previous decades (relative risk, 2.44 [95% confidence interval, 2.27-2.61]). The rate of endophthalmitis was 0.265% in the 2000-2003 period, 0.087% in the 1990s, 0.158% in the 1980s, and 0.327% during the 1970s. Furthermore, an upward trend in rates after 1992 was noted, compared with 1991 and prior. Incision type appeared to significantly influence risk, as endophthalmitis following clear corneal cataract extraction during the 1992-2003 period was 0.189% compared with 0.074% (relative risk, 2.55 [95% confidence interval, 1.75-3.71]) for scleral incision and 0.062% (relative risk, 3.06 [95% confidence interval, 2.48-3.76]) for limbal incision.
This systematic review indicates that the incidence of endophthalmitis associated with cataract extraction has increased over the last decade. This upward trend in endophthalmitis frequency coincides temporally with the development of sutureless clear corneal incisions.
To examine if changes in the diagnosis and management of postoperative endophthalmitis have occurred since 1995, and to identify factors that might predict final visual outcome.
Retrospective, population-based, noncomparative, consecutive case series.
Patients with clinically diagnosed endophthalmitis after cataract surgery and lens-related surgery in Western Australia from 1980 to 2000.
Endophthalmitis cases were identified using record linkage and cross-referencing with the surgical logbooks of vitreoretinal surgeons before validation by medical record review.
Microbiological data (microorganisms isolated and antibiotic susceptibilities), diagnostic interventions, surgical procedures, therapeutic interventions, and visual acuity (VA).
During the 21-year period, 213 episodes of endophthalmitis occurred after cataract surgery. Since 1995, both anterior chamber sampling and vitreous sampling have increased significantly. The overall use of vitrectomy has also increased, but we did not observe a difference according to presenting VA. Intravitreal antibiotic use increased significantly, whereas the use of both subconjunctival and IV antibiotics decreased. In one third of patients, the VA at least 6 months after admission for endophthalmitis was worse than 6/18. This was associated with treatment that did not include the use of oral antibiotics (odds ratio [OR], 3.86; 95% confidence interval [CI], 1.21-12.39; P = 0.02), growth from intraocular samples of organisms other than coagulase-negative staphylococci (OR, 9.84; 95% CI, 2.84-34.09; P<0.001), and a discharge VA worse than 6/18 (OR, 6.10; 95% CI, 1.63-22.89; P = 0.01).
Although we observed noticeable changes in the diagnosis and management of endophthalmitis since 1995, visual outcomes have not improved and remain poor. Our finding that treatment with oral antibiotics may be associated with a better visual outcome warrants further investigation.
To evaluate the in vitro susceptibility and cross-resistance of gatifloxacin and moxifloxacin vs older fluoroquinolones among coagulase-negative staphylococci recovered from patients with clinical endophthalmitis.
A combination of E tests and disk diffusion methods was used to determine in vitro susceptibility and cross-resistance for 111 coagulase-negative staphylococci isolates recovered during a 15-year period (January 1, 1990, to December 31, 2004) against 5 fluoroquinolones.
In vitro susceptibilities (percentage sensitive) in descending order were as follows: gatifloxacin, 74.5%; moxifloxacin, 72.1%; levofloxacin, 69.3%; ciprofloxacin, 65.6%, and ofloxacin, 60.4%. More than 65% of the coagulase-negative staphylococci resistant to ciprofloxacin (n = 38) demonstrated in vitro cross-resistance to gatifloxacin (25 [65.8%] of 38) and moxifloxacin (27 [71.1%] of 38). During the initial 5 years (January 1, 1990, to December 31, 1994), 96.6% of the coagulase-negative staphylococci were sensitive to gatifloxacin and moxifloxacin, with minimal inhibitory concentration required to inhibit or kill 90% of the isolates of 0.19 microg/mL and 0.12 microg/mL, respectively. During the last 5-year period (January 1, 2000, to December 31, 2004), the percentage of sensitive coagulase-negative staphylococci declined to 65.4% for gatifloxacin and moxifloxacin (P=.02). Minimal inhibitory concentration required to inhibit or kill 90% of the isolates was 32 microg/mL or greater for both drugs.
Gatifloxacin and moxifloxacin demonstrated an in vitro efficacy of less than 80% for coagulase-negative staphylococci endophthalmitis in the present study. Ciprofloxacin resistance may serve as a surrogate for concurrent in vitro resistance for gatifloxacin and moxifloxacin. Resistance increased significantly during the last 5 years. Declining in vitro susceptibility to gatifloxacin and moxifloxacin may have important implications for the prevention and treatment of postoperative endophthalmitis.
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The rates of PCE are low and range from 0.06% to 0.24%. This relatively low incidence of PCE renders it difficult to conduct prospective studies, investigating possible risk factors and effective prophylactic strategies. Currently, the only prophylaxis proven to decrease the incidence of PCE is the application of perioperative PVI. Prophylactic use of topical broad-spectrum antibiotics is commonly employed both preoperatively and postoperatively. Further prospective studies are needed to assess the usefulness of subconjunctival, intracameral, and irrigated antibiotics in cataract surgery. Variables such as incision type incision location, and use of suture also need to be further evaluated.
To investigate the antibiotic sensitivities and clinical outcomes of eyes with endophthalmitis caused by methicillin-sensitive versus methicillin-resistant Staphylococcus epidermidis (MSSE/MRSE).
A retrospective, consecutive case series of all patients with endophthalmitis caused by S. epidermidis from January 1, 1996, through July 1, 2004, was conducted. The antibiotic sensitivities and clinical outcomes were obtained from the corresponding medical records.
The study included 86 eyes of 86 patients with S. epidermidis endophthalmitis (34 MSSE and 52 MRSE). Endophthalmitis categories included cataract surgery (58), glaucoma surgery (12), trauma (7), vitrectomy (4), penetrating keratoplasty (4), and corneal suture ulcer (1). In vitro testing revealed that all MSSE and MRSE isolates were sensitive to vancomycin, 67% of MSSE isolates and 67% of MRSE isolates were sensitive to gatifloxacin, and 73% of MSSE isolates and 67% of MRSE isolates were sensitive to moxifloxacin (overall 68% sensitive). All eyes were treated with intravitreal vancomycin and either ceftazidime or amikacin. Visual acuity improved to a median of 20/80 at 3 months and 20/60 at 1 year. I CONCLUSIONS: In the current study, all MSSE and MRSE isolates were sensitive to vancomycin and 68% were sensitive to the fourth-generation fluoroquinolones. There were no significant differences in visual acuity outcomes of endophthalmitis caused by MSSE versus MRSE isolates.
To investigate the spectrum of organisms causing culture-proven endophthalmitis and their sensitivities to commonly used antimicrobial agents.
Retrospective, noncomparative, consecutive case series.
Medical records were reviewed of all patients with culture-proven endophthalmitis at a single institution between January 1, 1996, and December 31, 2001. Endophthalmitis categories included postoperative, posttraumatic, endogenous, and miscellaneous (for example, keratitis). The outcome measures included intravitreal isolates identified, antibiotic sensitivities, and category of endophthalmitis.
In all, 313 organisms were isolated from 278 patients during the study interval. The most common organisms identified were Staphylococcus epidermidis in 27.8% (87/313), Streptococcus viridans group in 12.8% (40/313), other coagulase-negative staphylococci in 9.3% (29/313), Staphylococcus aureus in 7.7% (24/313), and Propionibacterium acnes in 7.0% (22/313). Overall, 246 of 313 (78.5%) isolates were gram-positive organisms, 37 (11.8%) were gram-negative organisms, and 27 (8.6%) were fungi. For gram-positive organisms, sensitivities were the following: vancomycin 100%, gentamicin 78.4%, ciprofloxacin 68.3%, ceftazidime 63.6%, and cefazolin 66.8%. For gram-negative organisms, sensitivities were the following: ciprofloxacin 94.2%, amikacin 80.9%, ceftazidime 80.0%, and gentamicin 75.0%. Fungal isolates were Candida species (9/313), Aspergillus species (9/313), and other molds (9/313). Among the endophthalmitis categories, the most frequent organisms were the following: (1) acute-onset postoperative: S epidermidis, 46.9%; (2) delayed-onset postoperative: S epidermidis, 22.7%; (3) delayed-onset bleb-associated: fastidious gram-negative rods, 20.4%; (4) posttraumatic: S epidermidis, 20.8%; (5) endogenous: Aspergillus species, 20.8%; and (6) miscellaneous: molds (other), 36.4%.
In considering antibiotic treatment of endophthalmitis, it is important to recognize that no single antibiotic provided coverage for all of the microbes isolated from eyes with endophthalmitis. Combination therapy is recommended as the initial empiric treatment of suspected bacterial endophthalmitis. Appropriate history and characteristic clinical features may justify the use of initial antifungal agents. Knowledge of the most frequent causative organisms in various categories will help direct appropriate initial therapy.
- Ms Kresloff
- Aa Castellarin
- Ma Zarbin
- Endophthalmitis
Kresloff MS, Castellarin AA, Zarbin MA. Endophthalmitis.
Surv Ophthalmol 1998; 43(3): 193–224.
- D Miller
- Pm Flynn
- Iu Scott
- Ec Alfonso
- Flynn Jr
17 Miller D, Flynn PM, Scott IU, Alfonso EC, Flynn Jr HW.
In vitro fluoroquinolone resistance in staphylococcal endophthalmitis isolates. Arch Ophthalmol 2006; 124(4): 479–483.
Microbiologic spectrum and susceptibility of isolates: part I. Postoperative endophthalmitis. Endophthalmitis Research Group
- D Y Kunimoto
- T Das
- S Sharma
- S Jalali
- A B Majji
- U Gopinathan
- DY Kunimoto