Lessons learned from the anaerobe survey: historical perspective and review of the most recent data (2005-2007).

BACKGROUND: The rationale and lessons learned through the evolution of the National Survey for the Susceptibility of Bacteroides fragilis Group from its initiation in 1981 through 2007 are reviewed here. The survey was conceived in 1980 to track emerging antimicrobial resistance in Bacteroides species. METHODS: Data from the last 11 years of the survey (1997-2007), including 6574 isolates from 13 medical centers, were analyzed for in vitro antimicrobial resistance to both frequently used and newly developed anti-anaerobic agents. The minimum inhibitory concentrations of the antibiotics were determined using agar dilution in accordance with Clinical and Laboratory Standards Institute recommendations. RESULTS: The analyses revealed that the carbapenems (imipenem, meropenem, ertapenem, and doripenem) and piperacillin-tazobactam were the most active agents against these pathogens, with resistance rates of 0.9%-2.3%. In the most recent 3 years of the survey (2005-2007), resistance to some agents was shown to depend on the species, such as ampicillin-sulbactam against Bacteroides distasonis (20.6%) and tigecycline against Bacteroides uniformis and Bacteroides eggerthii ( approximately 7%). Very high resistance rates (>50%) were noted for moxifloxacin and trovafloxacin, particularly against Bacteroides vulgatus. During that period of study, non-B. fragilis Bacteroides species had >40% resistance to clindamycin. Metronidazole-resistant Bacteroides strains were also first reported during that period. CONCLUSIONS: In summary, resistance to antibiotics was greater among non-B. fragilis Bacteroides species than among B. fragilis and was especially greater among species with a low frequency of isolation, such as Bacteroides caccae and B. uniformis. The emergence of resistance among the non-B. fragilis Bacteroides species underscores the need for speciation of B. fragilis group isolates and for clinicians to be aware of associations between species and drug resistance.

Antibiotic resistance in urinary isolates of Escherichia coli from college women with urinary tract infections.

Of 176 urine isolates from female students positive for Escherichia coli, 29.6% were trimethoprim-sulfamethoxazole resistant and none were nitrofurantoin resistant. Among students with a history of urinary tract infection (UTI) (n = 119), resistance to ciprofloxacin was 11.8%, compared to 1.8% among those without prior UTI. Nitrofurantoin should be considered for empirical therapy of lower tract UTI.

Methicillin-resistant Staphylococcus aureus outbreak in an intensive care nursery: potential for interinstitutional spread.

BACKGROUND: After surveillance surveys documented the absence of methicillin-resistant Staphylococcus aureus (MRSA) in our intensive care nursery, an outbreak of MRSA infection occurred there during a 7-month period in 2005. METHODS: Control measures included reinforcement of hand hygiene and contact precautions procedures. Active surveillance cultures were obtained on all neonates, including interinstitutional transfers. A cohort unit was dedicated exclusively for neonates with MRSA. Pulsed-field gel electrophoresis was performed on isolates to determine relatedness. We surveyed transferring hospitals to evaluate MRSA activity and surveillance practices in their nurseries. RESULTS: Twenty-five neonates were colonized with MRSA; 9 of these had clinical infections. Isolates from 18 of 21 neonates from this outbreak and 4 neonates from a previous cluster were identical, including 1 isolate obtained upon transfer from another institution. Admission and discharge logs from a 9-month period showed that 127 of 460 admissions (27.6%) were admitted from 34 hospitals, and 247 of 460 (53.7%) were discharged to 32 hospitals. Among 30 transferring hospitals responding to our survey, MRSA activity occurred in 2 of 28 (7%) level 1 nurseries, 4 of 11 (36%) level 2 nurseries and 6 of 10 (60%) level 3 nurseries. Nine of the 30 hospitals (30%) performed some active surveillance. CONCLUSIONS: Interinstitutional transfer can play a role in the initiation and propagation of MRSA outbreaks in neonatal nurseries. The burden of MRSA in area nurseries and the rate of transfers affect the potential for interhospital spread of MRSA and may justify changes in policy regarding surveillance for MRSA and communication between hospitals.

Diagnosis of human congenital cytomegalovirus infection by amplification of viral DNA from dried blood spots on perinatal cards.

Congenital human cytomegalovirus (HCMV) infection affects 1% of children and is the most common infectious cause of sensorineural hearing loss. Due to the difficulty of diagnosing deafness and other neurological disorders in infants, affected individuals may not be recognized until much later when active infection has resolved and culture is no longer informative. To overcome this problem, congenital HCMV infection was diagnosed retrospectively by testing residual blood samples collected from newborns and dried on perinatal cards as part of the North Carolina Newborn Screening Program. We modified the Qiagen method for purifying DNA from dried blood spots to increase the sample size and recovery of the lysate. A multiplex, real-time TaqMan polymerase chain reaction assay on an ABI 7900 instrument measured a highly conserved segment of the HCMV polymerase gene and the APOB human control gene. HCMV DNA was detected in blood dried on perinatal cards from all seven infants with culture-proven congenital infection, and all 24 negative control cases lacked detectable HCMV DNA. Our findings suggest that it is possible to diagnose congenital HCMV infection using dried blood collected up to 20 months earlier. Further studies are warranted on patients with hearing loss or other neurological deficits to determine the percentage that is attributable to congenital HCMV infection.

Analysis of two- and three-year trends in antimicrobial resistance in intensive care units using unit-specific antibiograms.

Unit-specific antibiograms serve as useful guides to clinicians and infection control personnel. We compared trends in antimicrobial resistance in intensive care units using traditional 2-y unit-specific antibiogram data and 3 y of data. Three-y unit-specific antibiogram data may provide increased statistical power to detect changes in antimicrobial resistance.

Predictors of mortality in patients with bloodstream infection due to ceftazidime-resistant Klebsiella pneumoniae.

Bloodstream infection (BSI) due to multidrug-resistant Klebsiella is associated with high rates of morbidity and mortality. The aim of this study was to identify predictors of in-hospital mortality among patients with BSI due to ceftazidime-resistant (CAZ-R) Klebsiella pneumoniae at a tertiary care medical center. Patients with CAZ-R K. pneumoniae BSI were identified by our microbiology laboratory between January 1995 and June 2003. Clinical data were collected retrospectively. Logistic regression was used to identify independent predictors of all causes of in-hospital mortality. Of 779 patients with K. pneumoniae BSI, 60 (7.7%) had BSI due to CAZ-R K. pneumoniae; 43 (72%) of these were nosocomial infections. Pulsed-field gel electrophoresis identified a single predominant strain in 17 (28%) patients. The in-hospital mortality rate was 43% (n = 26). Among patients with CAZ-R K. pneumoniae BSI, those who died were similar to survivors with respect to demographic, clinical, and antimicrobial susceptibility characteristics. Only 43 (72%) patients received effective therapy within 5 days of BSI. In bivariable analysis, delay in initiation of effective therapy for >72 h after diagnosis of BSI was associated with death (P = 0.03). Strain genotype was not predictive of outcome. In multivariable analysis, delay in initiation of effective therapy for >72 h after diagnosis of BSI was an independent predictor of death (odds ratio, 3.32; 95% confidence interval, 1.07 to 10.3). Thus, among patients with BSI due to CAZ-R K. pneumoniae, a delay in the initiation of effective therapy of greater than 72 h after BSI was associated with a >3-fold increase in mortality risk.

Clinical profile and strain relatedness of recurrent enterococcal bacteremia.

We defined the molecular epidemiology of recurrent enterococcal bacteremia using pulsed field gel electrophoresis. We identified 27 patients, comprising 60 episodes; strain relatedness was demonstrated in 8 patients with isolates separated by up to 6 y. Carriage of pathogenic enterococci may be prolonged, although re-infection with novel strains is more commonly seen.

Sequential emergence of antibiotic resistance in enterococcal bloodstream isolates over 25 years.

We determined the antibiotic susceptibilities of 1,785 enterococcal bloodstream isolates collected over 25 years. Antibiotic resistance emerged at a greater rate in Enterococcus faecium than in other enterococcal species, and E. faecium isolates became proportionally more common over time. Our findings confirm the pattern of emerging antibiotic resistance among enterococci and highlight the increasing importance of E. faecium as a cause of bloodstream infection.

Comparison of microscan broth microdilution, synergy quad plate agar dilution, and disk diffusion screening methods for detection of high-level aminoglycoside resistance in enterococcus species.

We compared the dried MicroScan microdilution panel, Synergy Quad plate agar dilution, and high-potency disk diffusion screening methods for the detection of high-level aminoglycoside resistance in 815 enterococcal bloodstream isolates. Agreement between the three methods was 99% when testing for high-level gentamicin resistance and 96% when testing for high-level streptomycin resistance.

Multicenter evaluation of use of penicillin and ampicillin as surrogates for in vitro testing of susceptibility of enterococci to imipenem.

Imipenem is approved by the U.S. Food and Drug Administration (FDA) for treatment of infections caused by Enterococcus faecalis. However, there are no NCCLS guidelines for testing susceptibility of enterococci against imipenem. To assess whether or not ampicillin or penicillin could be used as a surrogate for broth microdilution (BMD) testing of imipenem versus Enterococcus species, 633 strains of E. faecalis, E. faecium, and other enterococci isolated from blood cultures of patients at three geographically distinct university hospitals were tested by the NCCLS BMD and disk diffusion (DD) methods. Using FDA susceptibility breakpoints for imipenem and NCCLS breakpoints for penicillin and ampicillin, categorical agreement (CA) for penicillin-imipenem and ampicillin-imipenem tested with E. faecalis and E. faecium by BMD was >/=94% but was /=98% and was 92% for other enterococci; CA for penicillin-imipenem was 91% for E. faecalis, 98% for E. faecium, and 87% for other enterococci. Further analysis showed that testing E. faecalis with ampicillin resulted in no false-susceptible (FS) or false-resistant (FR) results by BMD, no FS results by DD, and a single FR result by DD (0.2%), whereas testing with penicillin resulted in no FS results by BMD or DD and two FR results by BMD (0.4%). For E. faecium and other enterococci, the combination of FS and FR results was such that surrogate testing with penicillin or ampicillin appears not to be sufficiently reliable to be used clinically. We conclude that ampicillin is an accurate predictor of the in vitro activity of imipenem against E. faecalis.

Emergence of fluoroquinolone resistance among Bacteroides species.

BACKGROUND: Several newer generation fluoroquinolones have demonstrated good in vitro activity against Bacteroides species; particularly when first introduced. However, resistance of Bacteroides to quinolones appears to be increasing. MATERIALS AND METHODS: From 1994 to 2001, consecutive non-duplicated Bacteroides isolates from clinical specimens in 12 US hospitals were sent to the Tufts anaerobe laboratory for identification and susceptibility testing. NCCLS recommended methodology for testing was employed. Breakpoints of 8 mg/l for trovafloxacin and 4 mg/l for moxifloxacin were used to examine susceptibility trends. RESULTS: In total, 4434 isolates were analysed. The geometric mean MIC increased significantly for clinafloxacin, trovafloxacin and moxifloxacin. Resistance to trovafloxacin (breakpoint of 8 mg/l) and moxifloxacin (breakpoint of 4 mg/l) increased from 8% to 25% and from 30% to 43%, respectively. Increased resistance was observed for all Bacteroides species, for all sites of isolation, and in 11 of 12 participating hospitals. Bacteroides vulgatus and isolates from decubitus ulcers were associated with increased resistance. During 2001, trovafloxacin and moxifloxacin resistance among blood isolates was 27% and 52%, respectively. The association between increased resistance and year of isolation remained significant after adjustment for hospital, species and site of isolation. CONCLUSIONS: Fluoroquinolone resistance among Bacteroides isolated in the US has markedly increased during the years 1994 to 2001. High rates of resistance among blood isolates are of particular concern.