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M A Pfaller

Publications and source records attributed to M A Pfaller.

At least 235 records · Page 13Linked to original sources

Clinical evaluation of the ASTY colorimetric microdilution panel for antifungal susceptibility testing.

A method using a commercially prepared colorimetric microdilution panel (ASTY; Kyokuto Pharmaceutical Industrial Co., Ltd.) was compared in four different laboratories with the National Committee for Clinical Laboratory Standards (NCCLS) reference microdilution method by testing 802 clinical isolates of Candida spp. (C. albicans, C. glabrata, C. tropicalis, C. parapsilosis, C. krusei, C. lusitaniae, C. guilliermondii, C. lipolytica, C. rugosa, and C. zeylanoides) against amphotericin B, 5-fluorocytosine (5FC), fluconazole, and itraconazole. Reference MIC endpoints were established after 48 h of incubation, and ASTY endpoints were established after 24 and 48 h of incubation. ASTY endpoints were determined to be the time at which the color of the first well changed from red (indicating growth) to purple (indicating growth inhibition) or blue (indicating no growth). Excellent agreement (within 2 dilutions) between the reference and colorimetric MICs was observed. Overall agreement was 93% at 24 h and 96% at 48 h. Agreement ranged from 90% with itraconazole and 5FC to 96% with amphotericin B at 24 h and from 92% with itraconazole to 99% with amphotericin B and 5FC at 48 h. The ASTY colorimetric microdilution panel method appears to be comparable to the NCCLS reference method for testing the susceptibilities of Candida spp. to a variety of antifungal agents.

Amphotericin B↗

Therapy of Candida infections: susceptibility testing, resistance, and therapeutic options.

OBJECTIVE: Review the epidemiology of fungal infections, approved susceptibility testing methods, the scope of antifungal resistance, and advances in the treatment of fungal infections. DATA SOURCES: MEDLINE databases (from 1966 to March 1998) were searched for literature pertaining to the epidemiology and management of fungal infections. STUDY SELECTION AND DATA EXTRACTION: Articles were selected to assist in providing the reader an understanding of the epidemiology and management of fungal infections. DATA SYNTHESIS: Fungi have emerged as an important class of pathogens. Even though fungi rank as the fourth most commonly encountered nosocomial bloodstream pathogen, and are associated with the highest mortality of commonly encountered pathogens, only within the past year have methods for conducting and guidelines for interpreting in vitro susceptibility tests been approved. Under the guidance of these standards, we have begun to understand important issues regarding fungi such as the scope and mechanisms of antifungal resistance. Although there has not been a significant addition to our antifungal armamentarium since 1992, advances in antifungal therapy have been realized with the reformulation of available agents and the delineation of the pharmacodynamic characteristics of several antifungals. Additionally, several new agents, including a new class of antifungals, probably will enter into clinical use within the next 5 years. CONCLUSIONS: We have entered an era in which our understanding of fungi is increasing tremendously. Clinicians need to familiarize themselves with the current concepts surrounding the management of fungal infections in order to provide optimal care for their patients.

Antifungal Agents↗

Antifungal activity of a new triazole, voriconazole (UK-109,496), compared with three other antifungal agents tested against clinical isolates of filamentous fungi.

Voriconazole is a new triazole antifungal agent with potent activity against yeast and moulds. We investigated the in vitro activity of voriconazole, itraconazole, amphotericin B and 5-flucytosine against 51 clinical isolates of filamentous fungi. Overall, voriconazole was active (MIC50, 0.5 mg l(-1) and MIC90, 8 mg l(-1)) against these mould isolates. Voriconazole was most active against P. boydii (MIC50, 0.12 mg l(-1)) and Aspergillus spp. (MIC90, 0.5 mg l(-1)) and least active against Fusarium spp. (MIC90, 8 mg l(-1)) and Rhizopus spp. (MIC50, 8 mg l(-1)). Voriconazole was more active than amphotericin B against Aspergillus spp. and P. boydii. By comparison with itraconazole, voriconazole was more active against all isolates except Rhizopus spp. Based on these results, voriconazole has promising activity against commonly encountered isolates of filamentous fungi and its clinical usefulness should be established by further studies.

Amphotericin B↗

A 1994-95 survey of Haemophilus influenzae susceptibility to ten orally administered agents. A 187 clinical laboratory center sample in the United States.

During August, 1994 to April, 1995, a total of 2278 clinical isolates of Haemophilus influenzae were obtained from 187 clinical laboratories in the United States (U.S.). The vast majority of these isolates (75%) were from respiratory sites, and the remaining organisms were from blood, ear, eye, and spinal fluid sources. The overall rate of beta-lactamase production and ampicillin resistance was 36%. The antimicrobial susceptibility of isolates was determined by reference broth microdilution testing against ten orally administered agents. MIC values were compared according to 12 geographical regions, inpatient or outpatient status, gender, and eight age groupings. Modest and occasionally significant differences were observed: 1) greater numbers of beta-lactamase-producing strains among outpatients, in males, in the mid-Atlantic region, and in children < or = 12 years of age; 2) lower prevalence of beta-lactamase-producing isolates in the Southeast and Pacific regions; 3) cefaclor, cefprozil, and loracarbef activity was lowest among the younger children (< or = six years); and 4) macrolide in vitro efficacy was lowest in patients > 50 years of age and in three eastern regions. Overall, more than 99% of the strains were susceptible to amoxicillin/clavulanic acid, cefixime, and cefpodoxime (e.g., widest potential clinical use). Susceptibilities using National Committee for Clinical Laboratory Standards (NCCLS) breakpoint criteria for the other agents were: 96.6% to cefuroxime, 86.5% to loracarbef, 84.0% to clarithromycin, 81.8% to cefaclor, and 80.7% to cefprozil. Non-beta-lactamase mechanisms of resistance to ampicillin were rare (0.2%) or episodic and were attributed to altered penicillin-binding proteins. Although there is an increased prevalence of beta-lactamase production among H. influenzae isolates compared to prior years, four beta-lactams remain highly active (> 95% susceptibility) against contemporary strains of H. influenzae. Other monitored compounds seem to have declined in spectrum and surveillance trials for resistance among H. influenzae isolates should continue in an effort to identify trends in the U.S.

Adult↗

Variations in DNA subtype and antifungal susceptibility among clinical isolates of Candida tropicalis.

Candida tropicalis has been known to be a major cause of invasive Candida infection. Numerous reports have documented C. tropicalis as the most common species of Candida other than C. albicans. The epidemiology and antifungal susceptibility of C. tropicalis are poorly defined. A series of 89 clinical isolates of C. tropicalis from 56 patients hospitalized at seven different U.S. medical centers were analyzed by restriction endonuclease analysis of genomic DNA (REAG) using the restriction enzymes Sfil and BssHII followed by pulsed-field gel electrophoresis (PFGE). The MICs of the isolates for amphotericin B, 5-fluorocytosine (5FC), fluconazole, itraconazole, and D0870 were determined by microbroth dilution testing. A total of 49 different DNA types were identified among the 89 isolates. Generally, each DNA type represented an individual patient, and serial isolates from the same patient were the same DNA type. Small clusters of patients infected with the same DNA type of C. tropicalis suggested possible nosocomial transmission. The MICs of the various antifungal agents were amphotericin B 0.5 to 2.0 micrograms/ml (MIC90 = 2.0 micrograms/ml), 5FC 0.25 to 1.0 microgram/ml (MIC90 = 0.5 microgram/ml), fluconazole 0.25 to 8.0 micrograms/ml (MIC90 = 1.0 microgram/ml), itraconazole 0.03 to 1.0 microgram/ml (MIC90 = 0.5 microgram/ml), and D0870 0.007 to 0.12 microgram/ml (MIC90 = 0.03 microgram/ml). These data support previous observations that infections caused by C. tropicalis frequently originate from the patient's own endogenous flora. Clusters of a single strain in individual hospitals also suggests that limited nosocomial transmission may occur.

Amphotericin B↗

Evaluation of growth characteristics on blood agar and eosin methylene blue agar for the identification of Candida (Torulopsis) glabrata.

Candida albicans and Candida (Torulopsis) glabrata are the most common species of yeast encountered in the clinical laboratory. In this study, we sought to evaluate simple means of screening cultures for the presence or absence of C. glabrata. Twelve thousand five hundred (12,500) consecutive cultures were evaluated for sufficient yeast growth to warrant identification. When detected (369 isolates), the amount of growth on eosin methylene blue agar (EMB) versus sheep blood agar (BAP) (both incubated in 5% CO2), wet mount morphology, and germ tube production were evaluated. All germ tube-negative yeasts were definitively identified using the Vitek YBC card. Of the 369 yeast isolates included in this study, 225 were C. albicans, 102 C. glabrata, and 42 other Candida species. Growth on EMB was greater than BAP for 92 isolates; all identified as C. glabrata. When EMB growth was equal to or less than BAP, 10 isolates were C. glabrata and 267 were other Candida ssp. An accurate presumptive identification of C. glabrata may be made using the observation of greater growth on EMB versus BAP. When coupled with the germ tube test, the majority of yeast isolates could be identified by these simple methods in our laboratory.

Agar↗

Accuracy of the Vitek system for antimicrobial susceptibility testing Enterobacteriaceae bloodstream infection isolates: use of "direct" inoculation from Bactec 9240 blood culture bottles.

A recent investigation indicates that rapid antimicrobial susceptibility tests (AST) can affect patient therapy leading to reductions in health-care costs for some patient populations. However, there is little information relative to the often performed direct inoculation of positive blood culture bottles into rapid AST systems. AST results of direct inoculated Vitek (bioMerieux Vitek, Hazelwood, MO, USA) GNS cards were compared to those inoculated per package insert recommendations and a reference broth microdilution test using 50 consecutive Enterobacteriaceae bloodstream infection isolates. Escherichia coli (44% of isolates), Klebsiella ssp. (30%), and six other members of this family were tested against 15 antimicrobial agents. The direct inoculation method produced only two false-susceptible (0.3%), seven false-resistant (0.9%; six different drugs), and 48 minor errors (6.4%). The GNS cards inoculated in the usual, recommended manner had no very major error, and 7.5% combined major and minor errors. If the results of the urinary infection-specific drugs (nitrofurantoin, trimethoprim/sulfamethoxazole; not appropriate for bacteremia therapy) and ampicillin/sulbactam were deleted, both Vitek inoculation methods yielded results well within acceptable limits (< or = 4.5% overall error). These results indicate that the direct inoculation method of Vitek GNS cards from Enterobacteriaceae bloodstream infections (detected by Bactec 9240, Becton-Dickinson, Cockeysville, MD, USA) performed as well as the NCCLS broth microdilution test. Thus, a procedural modification of this type could further accelerate rapid access to accurate AST data.

Bacteremia↗

In vitro evaluation of contemporary beta-lactam drugs tested against viridans group and beta-haemolytic streptococci.

Streptococci continue to be prevalent causes of mild as well as of serious, life-threatening infections. Furthermore, some species harbor antimicrobial resistances (pneumococcus, viridans gr. streptococci) that compromise effective chemotherapy with beta-lactam drugs or other antimicrobial classes. In this study, the potency and spectrum of 12 beta-lactams was assessed versus 274 contemporary isolates of viridans group and beta-haemolytic streptococci using reference methods. Cefotaxime and ceftriaxone (MIC90s, 0.015 to 2 micrograms/ml, 84 to 100% susceptible) were consistently most potent among the agents tested. Ceftazidime (MIC90s, 0.25 to 8 micrograms/ml) and ticarcillin (MIC90s, 0.5 to > 32 micrograms/ml) were least active among the cephalosporins and penicillins, respectively. When 25% pooled serum was added to the reference test medium, ceftriaxone activity decreased fourfold, and cefotaxime remained highly active. As penicillin/beta-lactam-resistant streptococci with altered penicillin-binding protein target sites become more prevalent, only a few "third-generation" cephems seem to have sustained activity when used alone or possibly with a carefully selected co-drug. Routine testing of these species against beta-lactams and alternative drugs should be encouraged to detect emerging resistance patterns.

Ampicillin↗

Vancomycin-resistant Enterococcus raffinosus: molecular epidemiology, species identification error, and frequency of occurrence in a national resistance surveillance program.

Enterococcal blood stream infections are the third most common among all nosocomial blood stream infections in the United States and the occurrence of glycopeptide (vancomycin, teicoplanin) resistance in these isolates has markedly increased. Control of hospital-acquired infections with vancomycin-resistant enterococci requires high quality antimicrobial susceptibility test methods and species identification procedures as a supplement to epidemiologic investigation and appropriate infection control procedures. In this report, bacteremias caused by Enterococcus avium (BioMerieux Vitek, Hazelwood, MO, USA) were observed to be Enterococcus raffinosus infections (six of eight cases; 1.1% of all cases) when reference biochemical identification methods were applied. The vancomycin-susceptible E. raffinosis (two strains) and E. avium (two strains) had unique phenotypic and genotypic molecular profiles. In contrast, four vancomycin-resistant E. raffinosus strains (van A by polymerase chain reaction) from a single institution had the same phenotypic and molecular (PCR, PFGE, ribotyping) pattern, indicating clonal dissemination among four patients over a 66-day period. Clinical laboratories should be aware of the high probability that van A genes may be transferred from Enterococcus faecium or Enterococcus faecalis to other more rarely encountered Enterococcus species. Also contemporary, widely used commercial identification systems may fail to accurately identify those rare species. Errors appear to be most prevalent for E. avium, Enterococcus durans, and E. raffinosus based on the experience of the SCOPE Program.

Anti-Bacterial Agents↗

Inducible amp C beta-lactamase producing gram-negative bacilli from blood stream infections: frequency, antimicrobial susceptibility, and molecular epidemiology in a national surveillance program (SCOPE).

A surveillance study of nosocomial blood stream infections [Surveillance and Control of Pathogens of Epidemiologic Importance (SCOPE)] was conducted during a 14-month period in 1995 to 1996 in approximately 50 American medical centers. Among the 4725 blood stream infections, the etiologic agent was Enterobacter spp. in 230, Citrobacter freundii in 24, and Serratia marcescens in 65. The vast majority of these isolates (89%) had been sent to the University of Iowa including 198 Enterobacter spp. (46 Enterobacter aerogenes, 141 Enterobacter cloacae, 11 other Enterobacter spp.), 23 C. freundii, and 62 S. marcescens. Because these species are capable of producing Amp C beta-lactamase, we examined their susceptibility to 12 broad-spectrum antimicrobial agents. The frequency of resistance to ceftazidime and the molecular epidemiology of ceftazidime-resistant strains was also examined. Among the Enterobacter spp. and C. freundii isolates, resistance to third generation cephalosporins (ceftazidime, ceftriaxone) and broad-spectrum semisynthetic penicillins (piperacillin), with or without an enzyme inhibitor (piperacillin/tazobactam), was high, e.g., 35 to 50%. The S. marcescens isolates were quite susceptible to all agents tested. Both imipenem and cefepime were active against virtually all isolates tested including 84 stably derepressed Amp C-producing ceftazidime-resistant strains of Enterobacter spp. and C. freundii. The overall rank order of activity for the six best agents against these Amp C-producing strains was: imipenem (100% susceptible) > amikacin = cefepime (98.6%) > ciprofloxacin = gentamicin = ofloxacin (93.6 to 94.0%). Molecular typing studies of ceftazidime-resistant E. cloacae using an automated ribotyping system, as well as pulsed-field gel electrophoresis, indicated that although clonal spread of a single strain occurred in some of the medical centers, most of the episodes of bacteremia were caused by patient-unique strains. Control of these resistant organisms will require attention to microbiologic recognition of phenotypes, to infection control practices, and to limiting the overuse of certain extended spectrum beta-lactams.

Anti-Bacterial Agents↗

A review of the in vitro activity of meropenem and comparative antimicrobial agents tested against 30,254 aerobic and anaerobic pathogens isolated world wide.

The in vitro activity of meropenem (formerly SM-7738), a new carbapenem, was compared with that of imipenem and five other broad-spectrum antimicrobials (ceftazidime, cefotaxime, piperacillin, piperacillin/tazobactam, and ciprofloxacin) against 30,254 clinically significant pathogens isolated in nine countries worldwide. Overall, the carbapenems, meropenem and imipenem, were the most active drugs. Meropenem was four- to 64-fold more active than imipenem against Gram-negative bacteria, including the Enterobacteriaceae, Pseudomonas aeruginosa, Burkholderia cepacia, Haemophilus influenzae, and Neisseria meningitidis. Meropenem was also quite active against ceftazidime-resistant strains of Enterobacteriaceae, inhibiting 87.5 to 100% at < or = 4 micrograms/ml. In contrast, imipenem was four- to eight-fold more active than meropenem against Gram-positive species, including methicillin-susceptible strains of Staphylococcus aureus and Staphylococcus epidermidis, Streptococcus pneumoniae, and Enterococcus faecalis. Among the anaerobes, strains resistant to meropenem or imipenem were encountered very rarely. These extensive data provide additional in vitro support for the clinical use of meropenem as a broad spectrum antimicrobial agent active against key pathogenic species of bacteria.

Anti-Bacterial Agents↗

Nosocomial enterococcal blood stream infections in the SCOPE Program: antimicrobial resistance, species occurrence, molecular testing results, and laboratory testing accuracy. SCOPE Hospital Study Group.

Characteristics of nosocomial enterococcal blood stream infection (NEBSI) isolates obtained from patients at 41 U.S. hospitals participating in the SCOPE Program were studied. Isolates from 480 episodes of NEBSI were characterized according to species and antimicrobial susceptibility profile. Selected isolates were also identified to species and vancomycin resistance genotype using polymerase chain reaction based methods. Polymerase chain reaction genotyping and ribotyping were used as genetic markers for molecular epidemiologic typing. Enterococci were the third most common cause of nosocomial blood stream infection in this study, accounting for 11.7% of all isolates reported. Enterococcus faecalis was the most common species (59.6%), followed by E. faecium (19.4%). Species identification errors involving E. faecium, E. durans, E. avium, and E. raffinosus were observed. Vancomycin resistance was observed in 36.4% of all participating medical centers and varied from 11.1% of medical centers in the Northwest to 60.9% of medical centers in the Southwest. Vancomycin-resistant enterococci accounted for 20.6% of NEBSI in the Northeast, 11.4% in the Southeast, 11.1% in the Southwest, and 9.5% in the Northwest regions. VanA genotypes predominated in the Northeast and Southwest, whereas vanA and vanB genotypes were equally prevalent in the Northwest and Southeast. Molecular typing studies identified strains that were unique to individual hospitals as well as strains that were prevalent in several different hospitals. NEBSI with vancomycin-resistant enterococci continues to escalate among hospitalized patients in all geographic areas of the USA.

Anti-Bacterial Agents↗

In vitro activity of cefepime and ceftazidime against 197 nosocomial blood stream isolates of streptococci: a multicenter sample.

The increasing prevalence of streptococci as causes of potentially fatal nosocomial bacteremia requires that antimicrobial agents used for empiric therapy in hospitalized patients include both pneumococci and viridans group streptococci as well as beta-hemolytic streptococci in their activity profile. In this study, the in vitro activity of cefepime, a new fourth-generation cephalosporin, was compared with other cephalosporins versus 197 nosocomial blood stream isolates of streptococci (20 Streptococcus pneumoniae, 104 viridans group, and 73 beta-hemolytic) isolated from patients at more than 30 medial centers from 1995 to 1997. Additional agents tested included penicillin, erythromycin, and vancomycin. Overall, cefepime inhibited 83% of the isolates at concentrations < or = 0.5 microgram/mL and 100% at < or = 8 micrograms/mL. By comparison, ceftazidime inhibited 35 and 88% of isolates at the same concentrations. Cefepime was approximately eightfold more potent than ceftazidime against S. pneumoniae, viridans group streptococci, and beta-hemolytic streptococci. Among the 42 isolates with penicillin MICs > 0.12 microgram/mL, 100% were inhibited by cefepime and only 48% by ceftazidime at < or = 8 micrograms/mL. The rank order of activity for all six agents against the 197 isolates was vancomycin > ceftriaxone > cefepime > penicillin > erythromycin > ceftazidime. Based on the results of the present study, cefepime and ceftriaxone were the superior cephalosporins in potency and spectrum for empiric coverage of patients at risk for streptococcal blood stream infections.

Anti-Bacterial Agents↗

Growth medium effect on the antifungal activity of LY 303366.

The impact of growth medium selection on antifungal susceptibility testing has been well documented. Previously we described the antifungal characteristics of LY 303366 via time-kill curve methods using RPMI 1640 buffered with 0.165 M morpholinepropane-sulfonic acid as growth medium. The purpose of the current study was to compare the previously reported kill curve results with results obtained using antibiotic medium number three (AM #3) as growth medium. Antifungal activity was assessed via susceptibility testing and time-kill studies in both media. Two isolates each of Candida albicans, C. glabrata, and C. tropicalis were studied. MICs for the six isolates were found to be 10 to 100 times lower in AM #3. Time-kill studies were conducted with multiples of the MIC ranging from 0.125 x MIC to 16 x MIC. LY 303366 exhibited fungicidal (> or = 3 log10 reduction in CFU) activity against all isolates in AM #3; however, fungicidal activity was noted only for three of the six isolates when tested in RPMI. Furthermore, the rate of fungicidal activity was more rapid when AM #3 was utilized. Not only were the rate and extent of activity influenced by choice of media, but the relationships between LY 303366 concentrations and activity were also found to be media dependent. The findings from this study serve to highlight further the importance of media selection for in vitro evaluation of antifungal activity. In vivo studies need to be conducted with LY 303366 to determine which media provides the best correlation between in vitro and in vivo findings.

Anidulafungin↗

Multicenter evaluation of antimicrobial resistance to six broad-spectrum beta-lactams in Colombia using the Etest method. The Colombian Antimicrobial Resistance Study Group.

The need for comprehensive and quantitative accurate antimicrobial resistance surveillance systems has become acute as a guide to problem recognition and to focus local interventions. A multilaboratory (10 medical centers) Colombia surveillance project was initiated in early 1997 to monitor the potency and spectrum of six (cefepime, cefotaxime, ceftazidime, cefoperazone/sulbactam, aztreonam, and imipenem) broad-spectrum antimicrobial agents tested against 100 organisms per participant center (802 strains). Ten groups of organisms were tested by a reference-quality method (Etest; AB BIODISK, Solna, Sweden) with results validated by concurrent quality control and additional challenge strain analysis. Results from nine qualifying medical centers were tabulated, and 95.7 to 96.8% of quality assurance tests were within expected ranges. Only cefepime (90.1-100.0% susceptible) and imipenem (96.3-100.0%) were active against all Enterobacteriaceae at > 90% of susceptible isolates using the breakpoint concentrations recommended by the National Committee for Clinical Laboratory Standards. Among ceftazidime- (or cefotaxime- or aztreonam-) resistant Enterobacter spp. and Citrobacter freundii, cefepime remained active, but not cefoperazone with sulbactam. Escherichia coli and Klebsiella spp. strains having resistance phenotypes consistent with extended spectrum beta-lactamase production were discovered in approximately 5 to 10% of isolates. All tested drugs except ceftazidime (31.8-57.7% susceptible) were active against > 94% of oxacillin-susceptible staphylococci. Similar rates of resistance (9.1-14.8%) were observed in Pseudomonas aeruginosa for five of six drugs (not cefotaxime; 15.9% of strains were susceptible). Acinetobacter spp. isolates were most susceptible to imipenem (95.8%), cefepime (86.1%), and cefoperazone/sulbactam (83.3%). Overall for the 1997 order of antimicrobial spectrums for these tested compounds was: imipenem (96.6%) > cefepime (93.6%) > cefoperazone/sulbactam (90.5%) > cefotaxime (74.9%) > aztreonam (74.3% for Gram-negative bacilli only) > ceftazidime (73.2%). These data should be used to guide empiric regimens in Colombia, and additionally will provide a resistance statistical baseline to which future studies in this nation can be compared.

Anti-Bacterial Agents↗

Nosocomial streptococcal blood stream infections in the SCOPE Program: species occurrence and antimicrobial resistance. The SCOPE Hospital Study Group.

Nosocomial blood stream infections due to streptococci represent an increasingly important problem, particularly among neutropenic cancer patients. This problem is compounded by the emerging resistance to antimicrobial agents commonly used for empiric or prophylactic treatment of hospitalized patients. In this study, we examined the species distribution and antimicrobial susceptibility profile of 295 streptococcal nosocomial blood stream isolates from more than 30 U.S. medical centers (SCOPE National Surveillance Program). Streptococci accounted for 5.9% of all nosocomial blood stream isolates reported. The viridans group streptococci (VGS) were the most frequently isolated streptococci (50.8%), followed by the beta-haemolytic streptococci (31.9%) and pneumococci (13.2%). The beta-haemolytic streptococci were dominated by serogroup B strains (63%), followed by serogroups A and G. Of these organisms, 193 strains were referred for subsequent monitor susceptibility testing. Approximately 14% of S. pneumoniae, 9.2% of VGS, and 0% of beta-haemolytic streptococci were resistant to penicillin. Ceftriaxone was highly active against virtually all isolates (93-100% susceptible) except the VGS (77% susceptible). The rank order for activity of the four agents tested against the 193 isolates was vancomycin > ceftriaxone > penicillin > erythromycin. Importantly, 69% of the penicillin intermediate and resistant strains of VGS were also resistant to at least one additional antimicrobial (31% resistant to ceftriaxone, 51% resistant to erythromycin, 15% resistant to both ceftriaxone and erythromycin). The relatively poor activity of erythromycin against virtually all streptococci and the frequent association of macrolide resistance with penicillin resistance among the VGS suggests that both macrolides and beta-lactam agents might have limited value as prophylactic agents for dental procedures and in empiric or prophylactic use in neutropenic patients.

Anti-Bacterial Agents↗

An outbreak of Candida parapsilosis prosthetic valve endocarditis.

Candida parapsilosis, an important nosocomial pathogen and the most common species of Candida found on the hands of health care workers, is a rare cause of prosthetic valve endocarditis (PVE). From March through June 1994, four cases of C. parapsilosis PVE were diagnosed at a 400-bed community hospital. The mean time to presentation after valve replacement surgery was 148 days (range, 20 to 345). Three of the four patients died of complications of PVE. Multiple environmental cultures were performed, and only one was positive for C. parapsilosis. Cultures from the bypass pump, cell saver, cardioplegia solution, and subsequent valves were all negative. All valve replacements were performed by the same operating room team. Interviews with the surgeon and physician assistant, the only personnel involved in all cases, revealed that their hypoallergenic gloves were subject to frequent tears during valve replacement procedures, often requiring several glove changes per procedure. Hand cultures of personnel were obtained, and cultures from 20 individuals (26%) were positive for C. parapsilosis. Hand cultures of the surgeon and physician assistant obtained 8 months after the last case had surgery were negative for yeasts. Molecular typing of the 3 available case isolates, 14 epidemiologically unrelated patient isolates, 1 environmental isolate, and 20 hand isolates was performed by electrophoretic karyotyping and restriction endonuclease analysis of genomic DNA using restriction enzymes BssHII and EagI followed by pulsed field gel electrophoresis. The three case isolates were identical by restriction endonuclease analysis of genomic DNA, and two of the three shared the same electrophoretic karyotyping profile. The remaining patient, environmental, and hand isolates represented 29 different DNA types and were distinctly different from the case isolates. All of the isolates tested were susceptible to amphotericin B, 5FC, fluconazole, and itraconazole. The circumstantial evidence suggests the probability of glove tears during valve replacement surgery and subsequent transmission of C. parapsilosis to patients.

Aged↗

Antimicrobial activity of 12 broad-spectrum agents tested against 270 nosocomial blood stream infection isolates caused by non-enteric gram-negative bacilli: occurrence of resistance, molecular epidemiology, and screening for metallo-enzymes.

A total of 270 recent nosocomial blood stream isolates of non-Enterobacteriaceae Gram-negative bacilli representing nearly 50 U.S. medical centers were characterized. The numbers of isolates of individual organisms were: Pseudomonas aeruginosa (n = 204), Acinetobacter spp. (n = 48), and Stenotrophomonas maltophilia (n = 18). MICs were determined using the broth microdilution susceptibility method with 12 antimicrobial agents: piperacillin, piperacillin/tazobactam, ceftriaxone, ceftazidime, cefepime, imipenem, ciprofloxacin, ofloxacin, amikacin, gentamicin, tobramycin, and trimethoprim/sulfamethoxazole. Based on current National Committee for Clinical Laboratory Standards breakpoints, rates of resistance to cefepime, ceftazidime, and imipenem were as follows: P. aeruginosa, 3, 9, and 5%; Acinetobacter spp., 2, 37, and 0%; and S. maltophilia, 88.7, 35.3, and 100%, respectively. Trimethoprim/sulfamethoxazole was the most active agent against S. maltophilia (100% susceptible). Twenty-eight isolates of P. aeruginosa that expressed high levels of resistance to ceftazidime (MIC, > 256 micrograms/mL) and imipenem (MIC, > 32 micrograms/mL) were examined for potential metallo-beta-lactamase production by polymerase chain reaction and were found to be negative. Molecular typing of P. aeruginosa isolates revealed many patient-unique strains, but also noted clustering of infections due to isolates of the same DNA type, suggesting possible nosocomial transmission in 9 of 14 medical centers. Given the resistance profile and pathogenic potential of these non-enteric Gram-negative bacilli, considerable effort should be exerted to develop and enforce infection control and antimicrobial utilization practices that will limit the spread of these organisms in the hospital environment.

Acinetobacter↗