Search PubMed⌕ Search

Biomedical subjects

M A Pfaller

Publications and source records attributed to M A Pfaller.

At least 73 records · Page 4Linked to original sources

Age-related trends in pathogen frequency and antimicrobial susceptibility of bloodstream isolates in North America: SENTRY Antimicrobial Surveillance Program, 1997-2000.

We report age-related trends in pathogen frequency and antimicrobial susceptibility from 25,745 bloodstream infections (BSI) due to bacterial pathogens reported from medical centres participating in the North American SENTRY Antimicrobial Surveillance Program between January 1997 and September 2000. Staphylococcus aureus, Escherichia coli and coagulase-negative staphylococci (CoNS) were the most common pathogens, together accounting for 55% of all BSI pathogens during this time period. Among nosocomial BSI, CoNS were the most frequently isolated pathogens in infants less than 1 year of age, but S. aureus increased in frequency with increasing age. Among community-onset BSI pathogens, Streptococcus pneumoniae was the most frequently reported pathogen causing BSI in patients aged 1-5, S. aureus among those aged 6-64, and E. coli predominated at the extremes of age (less than 1 year and > or = 65 years of age). Among key organism: antimicrobial agent combinations evaluated, oxacillin resistance in S. aureus increased with increasing age; conversely, oxacillin resistance among CoNS was highest among children 5 years of age or younger. Penicillin resistance among S. pneumoniae BSI was highest in children younger than 5 years, while vancomycin resistance among Enterococcus spp. predominated among nosocomial BSI in patients over 50 years of age. Important age-related differences exist in species distribution and antimicrobial susceptibility of pathogens causing BSI. This information should be helpful for clinicians as they consider empirical antimicrobial therapy for patients with suspected BSI across the age continuum.

Adolescent↗

Comparison of Etest, chequerboard dilution and time-kill studies for the detection of synergy or antagonism between antifungal agents tested against Candida species.

Currently, there is considerable debate regarding the best in vitro method for testing antifungal combinations against Candida spp. In this study, we compared the results obtained by chequerboard dilution, time-kill studies and Etest for several antifungal combinations against Candida spp. Three Candida albicans isolates (fluconazole MICs of 1.0, 32 and >256 mg/L) and three non-albicans Candida isolates (C. glabrata, C. tropicalis and C. krusei) were tested in RPMI 1640 medium. By chequerboard testing, the majority of antifungal combinations were found to be indifferent. Notably, antagonism was identified by time-kill studies and by Etest for combinations of amphotericin B-fluconazole, but it was not detected by the chequerboard method. Pre-exposure of isolates to fluconazole did not affect results of the Etest or chequerboard method, but it did increase the frequency of antagonism noted by time-kill methods. This study indicates that chequerboard dilution testing in RPMI medium may not reliably detect the attenuation of amphotericin B activity. Of the three methods, Etest was the simplest to use and yielded reproducible results for testing antifungal combinations.

Amphotericin B↗

In vitro activities of 5-fluorocytosine against 8,803 clinical isolates of Candida spp.: global assessment of primary resistance using National Committee for Clinical Laboratory Standards susceptibility testing methods.

We determined the in vitro activity of flucytosine (5-fluorocytosine [5FC]) against 8,803 clinical isolates of Candida spp. (18 species) obtained from more than 200 medical centers worldwide between 1992 and 2001. The MICs were determined by broth microdilution tests performed according to NCCLS guidelines by using RPMI 1640 as the test medium and the following interpretive breakpoints: susceptible (S), < or =4 micro g/ml; intermediate (I), 8 to 16 micro g/ml; resistant (R), > or =32 micro g/ml. 5FC was very active against the 8,803 Candida isolates (MIC(90), 1 micro g/ml), 95% S. A total of 99 to 100% of C. glabrata (MIC(90), 0.12 micro g/ml), C. parapsilosis (MIC(90), 0.25 micro g/ml), C. dubliniensis (MIC(90), 0.12 micro g/ml), C. guilliermondii (MIC(90), 0.5 micro g/ml), and C. kefyr (MIC(90), 1 micro g/ml) were susceptible to 5FC at the NCCLS breakpoint. C. albicans (MIC(90), 1 micro g/ml; 97% S) and C. tropicalis (MIC(90), 1 micro g/ml; 92% S) were only slightly less susceptible. In contrast, C. krusei was the least susceptible species: 5% S; MIC(90), 32 micro g/ml. Primary resistance to 5FC is very uncommon among Candida spp. (95% S, 2% I, and 3% R), with the exception of C. krusei (5% S, 67% I, and 28% R). The in vitro activity of 5FC, combined with previous data demonstrating a prolonged post-antifungal effect (2.5 to 4 h) and concentration-independent activity (optimized at 4x MIC), suggest that 5FC could be used in lower doses to reduce host toxicity while maintaining antifungal efficacy.

Antifungal Agents↗

Antifungal activities of posaconazole, ravuconazole, and voriconazole compared to those of itraconazole and amphotericin B against 239 clinical isolates of Aspergillus spp. and other filamentous fungi: report from SENTRY Antimicrobial Surveillance Program, 2000.

Posaconazole, ravuconazole, and voriconazole are new triazole derivatives that possess potent, broad-spectrum antifungal activity. We evaluated the in vitro activity of these investigational triazoles compared with that of itraconazole and amphotericin B against 239 clinical isolates of filamentous fungi from the SENTRY Program, including Aspergillus spp. (198 isolates), Fusarium spp. (7 isolates), Penicillium spp. (19 isolates), Rhizopus spp. (4 isolates), Mucor spp. (2 isolates), and miscellaneous species (9 isolates). The isolates were obtained from 16 different medical centers in the United States and Canada between January and December 2000. In vitro susceptibility testing was performed using the microdilution broth method outlined in the National Committee for Clinical Laboratory Standards M38-P document. Overall, posaconazole was the most active compound, inhibiting 94% of isolates at a MIC of < or = 1 microg/ml, followed by voriconazole (91%), amphotericin B (89%), ravuconazole (88%), and itraconazole (70%). All three new triazoles demonstrated excellent activity (MIC, < or = 1 microg/ml) against Aspergillus spp. (114 Aspergillus fumigatus, 22 Aspergillus niger, 13 Aspergillus flavus, 9 Aspergillus versicolor, 8 Aspergillus terreus, and 32 Aspergillus spp.): posaconazole (98%), voriconazole (98%), ravuconazole (92%), amphotericin B (89%), and itraconazole (72%). None of the triazoles were active against Fusarium spp. (MIC at which 50% of the isolates tested were inhibited [MIC(50)], >8 microg/ml) or Mucor spp. (MIC(50), >8 microg/ml). Posaconazole and ravuconazole were more active than voriconazole against Rhizopus spp. (MIC(50), 1 to 2 microg/ml versus >8 microg/ml, respectively). Based on these results, all three new triazoles exhibited promising activity against Aspergillus spp. and other less commonly encountered isolates of filamentous fungi. The clinical value of these in vitro data remains to be seen, and in vitro-in vivo correlation is needed for both new and established antifungal agents. Surveillance efforts should be expanded in order to monitor the spectrum of filamentous fungal pathogens and their in vitro susceptibility as these new antifungal agents are introduced into clinical use.

Amphotericin B↗

In vitro activities of ravuconazole and voriconazole compared with those of four approved systemic antifungal agents against 6,970 clinical isolates of Candida spp.

The in vitro activities of ravuconazole and voriconazole were compared with those of amphotericin B, flucytosine (5FC), itraconazole, and fluconazole against 6,970 isolates of Candida spp. obtained from over 200 medical centers worldwide. Both ravuconazole and voriconazole were very active against all Candida spp. (MIC at which 90% of the isolates tested are inhibited [MIC(90)], 0.25 microg/ml; 98% of MICs were < or 1 microg/ml); however, a decrease in the activities of both of these agents was noted among isolates that were susceptible-dose dependent (fluconazole MIC, 16 to 32 microg/ml) and resistant (MIC, > or = 64 microg/ml) to fluconazole. Candida albicans was the most susceptible species (MIC(90) of both ravuconazole and voriconazole, 0.03 microg/ml), and C. glabrata was the least susceptible species (MIC(90), 1 to 2 microg/ml). Ravuconazole and voriconazole were each more active in vitro than amphotericin B, 5FC, itraconazole, and fluconazole against all Candida spp. and were the only agents with good in vitro activity against C. krusei. These results provide further evidence for the spectrum and potency of ravuconazole and voriconazole against a large and geographically diverse collection of Candida spp.

Antifungal Agents↗

Precision and accuracy of fluconazole susceptibility testing by broth microdilution, Etest, and disk diffusion methods.

Interpretive agreements among the results of fluconazole broth microdilution tests, Etests, and disk diffusion tests were documented by evaluating 495 Candida spp. Microdilution reference test results were in agreement with 96% of the Etest results; most discrepancies were minor differences. Fluconazole resistance of Candida krusei strains often required a full 48 h of incubation in order to be observed by the standard method. For the disk diffusion tests that were performed on Mueller-Hinton agar with glucose and methylene blue, 97% of results were in agreement with those of the reference test, especially when zones of inhibition were measured after the first 24 h of incubation. Some Candida glabrata isolates failed to grow satisfactorily until a full 48 h of incubation was completed. Precision was determined by testing 50 selected isolates in triplicate in each of three laboratories. The reproducibility of results of disk diffusion tests was comparable to that of the reference method. With all procedures, determination of test results was particularly challenging with some strains, and new methods are needed in order to improve endpoint definition.

Agar↗

Molecular epidemiology of extended-spectrum beta-lactamase-producing, fluoroquinolone-resistant isolates of Klebsiella pneumoniae in Taiwan.

Strains of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) have emerged worldwide. Concomitant ciprofloxacin resistance with ESBL production in K. pneumoniae isolates would severely restrict treatment options. Among 39 (18.5%) of 211 ESBL-KP isolates resistant to ciprofloxacin (MIC, >/=4 micro g/ml), 37 (95%) were high level resistant (MIC, >/=16 micro g/ml). These isolates were also cross resistant to the newer fluoroquinolones, including levofloxacin, gatifloxacin, gemifloxacin, and garenoxacin (BMS 284756). Sitafloxacin was most active against these ciprofloxacin-resistant ESBL-KP isolates with MICs for 67% of the isolates being </=2 micro g/ml. The molecular epidemiology of these multiresistant isolates was investigated by automated ribotyping and pulsed-field gel electrophoresis (PFGE). Ribotyping identified 18 different strains among the 39 ciprofloxacin-resistant ESBL-KP isolates. The majority (67%) of these isolates were contained in six ribogroups which were further confirmed by PFGE. The distribution of the six major strains of ciprofloxacin-resistant ESBL-KP within Taiwan included one (ribogroup 255.3-PFGE type E) with a nationwide distribution and several institution-specific strains. Interhospital cooperation appears necessary, with strict infection control practices coupled with restriction of fluoroquinolone and extended-spectrum beta-lactam use to control both the major epidemic strain and the more diverse strains observed within individual institutions.

Anti-Infective Agents↗

Trends in antifungal susceptibility of Candida spp. isolated from pediatric and adult patients with bloodstream infections: SENTRY Antimicrobial Surveillance Program, 1997 to 2000.

From 1 January 1997 through 31 December 2000, 2,047 bloodstream infections (BSIs) due to Candida spp. were reported from hospitals in the United States, Canada, Latin America, and Europe participating in the SENTRY Antifungal Surveillance Program. Among individuals in four age groups (< or =1, 2 to 15, 16 to 64, and > or =65 years) Candida albicans was the most common species, causing 60, 55, 55, and 50% of infections, respectively. C. glabrata caused 17 to 23% of BSIs in those ages 16 to 64 and > or = 65 years, whereas it caused only 3% of BSIs in the individuals in the two younger age groups (P < 0.001). C. parapsilosis (which caused 21 to 24% of BSIs) and C. tropicalis (which caused 7 to 10% of BSIs) were more common than C. glabrata in individuals ages < or =1 year and 2 to 15 years. Isolates of Candida spp. showed a trend of decreasing susceptibility to fluconazole, itraconazole, and amphotericin B with increasing patient age (P < or = 0.01). None of the C. glabrata isolates from individuals < or =1 year old were resistant to fluconazole, whereas they made up 5 to 9% of isolates from individuals ages 16 to 64 and > or =65 years. Isolates of C. tropicalis from patients < or =1 year old were more susceptible to flucytosine (MIC at which 90% of isolates are inhibited [MIC(90)], 0.5 microg/ml; 0% resistant isolates) than those from patients > or =65 years old (MIC(90), 32 microg/ml; 11% resistant isolates). The investigational triazoles posaconazole, ravuconazole, and voriconazole were all highly active against all species of Candida from individuals in all age groups. These data demonstrate differences in the species distributions of pathogens and differences in antifungal resistance among isolates from individuals in the pediatric and adult age groups. Ongoing surveillance will enhance efforts to limit the extent of antifungal resistance in individuals in various age groups.

Adolescent↗

Epidemiology of candidemia: 3-year results from the emerging infections and the epidemiology of Iowa organisms study.

Bloodstream infections due to Candida species cause significant morbidity and mortality. Surveillance for candidemia is necessary to detect trends in species distribution and antifungal resistance. We performed prospective surveillance for candidemia at 16 hospitals in the State of Iowa from 1 July 1998 through 30 June 2001. Using U.S. Census Bureau and Iowa Hospital Association data to estimate a population denominator, we calculated the annual incidence of candidemia in Iowa to be 6.0 per 100,000 of population. Candida albicans was the most common species detected, but 43% of candidemias were due to species other than C. albicans. Overall, only 3% of Candida species were resistant to fluconazole. However, Candida glabrata was the most commonly isolated species other than C. albicans and demonstrated some resistance to azoles (fluconazole MIC at which 90% of the isolates tested are inhibited, 32 microg/ml; 10% resistant, 10% susceptible dose dependent). C. glabrata was more commonly isolated from older patients (P = 0.02) and caused over 25% of candidemias among persons 65 years of age or older. The investigational triazoles posaconazole, ravuconazole, and voriconazole had excellent in vitro activity overall against Candida species. C. albicans is the most important cause of candidemia and remains highly susceptible to available antifungal agents. However, C. glabrata has emerged as an important and potentially antifungal resistant cause of candidemia, particularly among the elderly.

Adolescent↗

Clinical evaluation of a frozen commercially prepared microdilution panel for antifungal susceptibility testing of seven antifungal agents, including the new triazoles posaconazole, ravuconazole, and voriconazole.

A commercially prepared frozen broth microdilution panel (Trek Diagnostic Systems, Westlake, Ohio) was compared with a reference microdilution panel for antifungal susceptibility testing of two quality control (QC) strains and 99 clinical isolates of Candida spp. The antifungal agents tested included amphotericin B, flucytosine, fluconazole, itraconazole, posaconazole, ravuconazole, and voriconazole. Microdilution testing was performed according to NCCLS recommendations. MIC endpoints were read visually after 48 h of incubation and were assessed independently for each microdilution panel. The MICs for the QC strains were within published limits for both the reference and Trek microdilution panels. Discrepancies among MIC endpoints of no more than 2 dilutions were used to calculate the percent agreement. Acceptable levels of agreement between the Trek and reference panels were observed for all antifungal agents tested against the 99 clinical isolates. The overall agreement for each antifungal agent ranged from 96% for ravuconazole to 100% for amphotericin B. The Trek microdilution panel appears to be a viable alternative to frozen microdilution panels prepared in-house.

Antifungal Agents↗

Minimizing the workup of blood culture contaminants: implementation and evaluation of a laboratory-based algorithm.

An algorithm was implemented in the clinical microbiology laboratory to assess the clinical significance of organisms that are often considered contaminants (coagulase-negative staphylococci, aerobic and anaerobic diphtheroids, Micrococcus spp., Bacillus spp., and viridans group streptococci) when isolated from blood cultures. From 25 August 1999 through 30 April 2000, 12,374 blood cultures were submitted to the University of Iowa Clinical Microbiology Laboratory. Potential contaminants were recovered from 495 of 1,040 positive blood cultures. If one or more additional blood cultures were obtained within +/-48 h and all were negative, the isolate was considered a contaminant. Antimicrobial susceptibility testing (AST) of these probable contaminants was not performed unless requested. If no additional blood cultures were submitted or there were additional positive blood cultures (within +/-48 h), a pathology resident gathered patient clinical information and made a judgment regarding the isolate's significance. To evaluate the accuracy of these algorithm-based assignments, a nurse epidemiologist in approximately 60% of the cases performed a retrospective chart review. Agreement between the findings of the retrospective chart review and the automatic classification of the isolates with additional negative blood cultures as probable contaminants occurred among 85.8% of 225 isolates. In response to physician requests, AST had been performed on 15 of the 32 isolates with additional negative cultures considered significant by retrospective chart review. Agreement of pathology resident assignment with the retrospective chart review occurred among 74.6% of 71 isolates. The laboratory-based algorithm provided an acceptably accurate means for assessing the clinical significance of potential contaminants recovered from blood cultures.

Algorithms↗

Comparative antimicrobial spectrum and activity of BMS284756 (T-3811; a desfluoroquinolone) tested against an international collection of staphylococci and enterococci, including in vitro test development and intermethod comparisons.

The study was initiated to determine the in vitro activity and MIC/disk test comparisons of BMS284756, a new des-fluoro(6)-quinolone, against isolates of staphylococci and enterococci from the SENTRY Antimicrobial Surveillance Program, 2000. Isolates were tested by reference broth microdilution and standardized disk diffusion methods. Against 3,789 strains of gram-positive cocci from the SENTRY Program (2000), the BMS284756 MIC90 and percentage susceptible at < or = 2 and < or = 4 microg/ml were: Staphylococcus aureus (4 microg/ml; 89.3 and 97.1%), coagulase-negative staphylococci (CoNS; 4 microg/ml; 86.1 and 96.0%) and enterococci (> 4 microg/ml; 62.0 and 76.2%). Also tested were selected staphylococci (300 strains) and enterococci (102 strains) by two standardized methods. The activity of BMS284756 was highly correlated with oxacillin resistance among staphylococci. Oxacillin-susceptible staphylococci were all inhibited by BMS284756 at < or = 0.5 microg/ml, whereas oxacillin-resistant strains required inhibitory concentrations of > or = 1 microg/ml. Excellent correlation was observed between the MIC and 5-microg disk zone diameter for staphylococci and enterococci (r=0.91 to 0.93). Among vancomycin-susceptible enterococci, 67% of Enterococcus faecalis, 25% of E. faecium, and 76% of other Enterococcus spp. isolates were inhibited by BMS284756 at < or = 2 microg/ml. All vancomycin-resistant enterococci (VRE; 11 E. faecalis and 15 E. faecium) were inhibited by > or = 2 microg/ml of BMS284756. Among the non-VRE, non-faecium enterococcal isolates (n=64), 62% were inhibited by < or = 0.5 microg/ml. BMS284756 showed excellent activity against oxacillin-susceptible staphylococci and moderate activity against enterococci other than VRE and E. faecium. Acceptable correlations were observed between MIC and disk test results for both tested genus groups.

Anti-Infective Agents↗

Frequency of pathogen occurrence and antimicrobial susceptibility among community-acquired respiratory tract infections in the respiratory surveillance program study: microbiology from the medical office practice environment.

Continuing problems of antimicrobial resistance have prompted the initiation of several surveillance programs. Few, if any, of these programs focus on community-acquired respiratory tract infections seen in routine office-based practices. The Respiratory Surveillance Program (RESP; 1999-2000) in 674 community-based physician office practices in the United States determined the frequency of potential bacterial pathogens including Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in patients diagnosed clinically with community-acquired pneumonia, acute exacerbations of chronic bronchitis, and sinusitis throughout all 9 US census/geographic regions. Susceptibility to the penicillins (ampicillin, penicillin), oral cephalosporins, fluoroquinolones (gatifloxacin, levofloxacin, ciprofloxacin), macrolides (erythromycin, azithromycin, clarithromycin), tetracycline, and trimethoprim/sulfamethoxazole was determined by reference methods. Patients were required to have a culturable focus of infection, and specimens were immediately sent to a reference laboratory. Among 22,689 total specimens (610 community-acquired pneumonia, 4,779 acute exacerbation of chronic bronchitis, 16,213 sinusitis, 1,087 other), H influenzae was the most commonly isolated organism from patients with community-acquired pneumonia (38%) and acute exacerbation of chronic bronchitis (35%) in all nine geographic regions. S pneumoniae was isolated in 18% of community-acquired pneumonia cases, 13% of acute exacerbation of chronic bronchitis cases, and 11% of sinusitis cases. M catarrhalis was most commonly isolated from the nasopharynx of patients with sinusitis (29%). High-level resistance to penicillin (2 microg/mL or greater; 16% overall) and the macrolides (32% to 35%) among S pneumoniae varied both with site of infection and with geographic region. The greatest resistance was observed among isolates from the nasopharynx of patients with sinusitis and from patients from the East South Central or South Atlantic regions of the United States. Although the susceptibility of H influenzae and M catarrhalis to the tested antimicrobials did not vary with the type of infection, beta-lactamase-mediated resistance to ampicillin among H influenzae ranged from 15% in New England to 32% in the East South Central region. The fluoroquinolones were highly active against these cultured isolates from community-acquired respiratory tract infection patients, with >99% of all S pneumoniae, H influenzae, and M catarrhalis strains susceptible to gatifloxacin (MIC(90), 0.5 microg/mL) and levofloxacin (MIC(90), 2 microg/mL). The extended-spectrum fluoroquinolones appear well suited for community-acquired respiratory tract infection therapy, including pathogens other than pneumococcus, H influenzae, and M catarrhalis.

Adolescent↗

The molecular epidemiology of penicillin-resistant Streptococcus pneumoniae in the United States, 1994-2000.

The genetic relatedness of 672 penicillin-resistant isolates of Streptococcus pneumoniae (PRSP) recovered during national surveillance studies conducted in the United States during the periods of 1994-1995, 1997-1998, and 1999-2000 was determined by use of pulsed-field gel electrophoresis (PFGE). Overall, 104 different PFGE types were elucidated. For all study periods combined, the 12 most prevalent PFGE types included >75% of all isolates, and 5 types were closely related to widespread clones (Spain(23F)-1, France(9V)-3, Spain(6B)-2, Tennessee(23F)-4, and Taiwan(19F)-14). From 1994-1995 to 1999-2000, 3 major PFGE types (not closely related to 16 recognized clones) increased in prevalence. Multidrug resistance was identified among 96%-100% of the isolates in 9 of 12 predominant PFGE types. The prevalence of erythromycin resistance increased within 4 major PFGE types. These observations support the hypothesis that the dominant factor in the emergence of PRSP in the United States during the 1990s has been human-to-human spread of relatively few clonal groups that harbor resistance determinants to multiple classes of antibiotics.

Adolescent↗

Risk factors for candidal bloodstream infections in surgical intensive care unit patients: the NEMIS prospective multicenter study. The National Epidemiology of Mycosis Survey.

To assess risk factors for development of candidal blood stream infections (CBSIs), a prospective cohort study was performed at 6 sites that involved all patients admitted to the surgical intensive care unit (SICU) for >48 h over a 2-year period. Among 4276 such patients, 42 CBSIs occurred (9.82 CBSIs per 1000 admissions). The overall incidence was 0.98 CBSIs per 1000 patient days and 1.42 per 1000 SICU days with a central venous catheter in place. In multivariate analysis, factors independently associated with increased risk of CBSI included prior surgery (relative risk [RR], 7.3), acute renal failure (RR, 4.2), receipt of parenteral nutrition (RR, 3.6), and, for patients who had undergone surgery, presence of a triple lumen catheter (RR, 5.4). Receipt of an antifungal agent was associated with decreased risk (RR, 0.3). Prospective clinical studies are needed to identify which antifungal agents are most protective and which high-risk patients will benefit from antifungal prophylaxis.

Adolescent↗

Survey of infections due to Staphylococcus species: frequency of occurrence and antimicrobial susceptibility of isolates collected in the United States, Canada, Latin America, Europe, and the Western Pacific region for the SENTRY Antimicrobial Surveillance Program, 1997-1999.

Between January 1997 and December 1999, bloodstream isolates from 15,439 patients infected with Staphylococcus aureus and 6350 patients infected with coagulase-negative Staphylococcus species (CoNS) were referred by SENTRY-participating hospitals in the United States, Canada, Latin America, Europe, and the Western Pacific region. S. aureus was found to be the most prevalent cause of bloodstream infection, skin and soft-tissue infection, and pneumonia in almost all geographic areas. A notable increase in methicillin (oxacillin) resistance among community-onset and hospital-acquired S. aureus strains was observed in the US centers. The prevalence of methicillin (oxacillin)-resistant S. aureus varied greatly by region, site of infection, and whether the infection was nosocomial or community onset. Rates of methicillin resistance were extremely high among S. aureus isolates from centers in Hong Kong and Japan. Uniformly high levels of methicillin resistance were observed among CoNS isolates. Given the increasing multidrug resistance among staphylococci and the possible emergence of vancomycin-resistant strains, global strategies are needed to control emergence and spread of multiply resistant staphylococci.

Anti-Bacterial Agents↗

Integration of molecular characterization of microorganisms in a global antimicrobial resistance surveillance program.

The SENTRY Antimicrobial Surveillance Program has incorporated molecular strain typing and resistance genotyping as a means of providing additional information that may be useful for understanding pathogenic microorganisms worldwide. Resistance phenotypes of interest include multidrug-resistant pathogens, extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci, and fluoroquinolone-resistant (FQR) strains of gram-negative bacilli and Streptococcus pneumoniae. Clusters of > or =2 isolates within a given resistance profile that are linked temporally and by hospital location are flagged for DNA fingerprinting. Further characterization of organisms with respect to resistance genotype is accomplished with use of polymerase chain reaction and DNA sequencing. This process has been highly successful in identifying clonal spread within clusters of multiresistant pathogens. Between 50% and 90% of MRSA clusters identified by phenotypic screening contained evidence of clonal spread. Among the Enterobacteriaceae, ESBL-producing strains of Escherichia coli and Klebsiella pneumoniae are the most common pathogens causing clusters of infection, and approximately 50% of recognized clusters demonstrate clonal spread. Clusters of Pseudomonas aeruginosa, Acinetobacter species, and Stenotrophomonas maltophilia have been noted with clonal spread among patients with urinary tract, respiratory, and bloodstream infections. Characterization of mutations in the FQR-determining region of phenotypically susceptible isolates of E. coli and S. pneumoniae has identified first-stage mutants among as many as 40% of isolates. The ability to characterize organisms phenotypically and genotypically is extremely powerful and provides unique information that is important in a global antimicrobial surveillance program.

Bacterial Infections↗