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Fred C Tenover

Publications and source records attributed to Fred C Tenover.

At least 37 records · Page 2Linked to original sources
PubMed2005

Vancomycin-resistant staphylococci and enterococci: epidemiology and control.

PURPOSE OF REVIEW: This review updates information on the development and spread of vancomycin resistance in staphylococci and enterococci. RECENT FINDINGS: New information on the genetic characterization of vancomycin-resistant Staphylococcus aureus isolates from the US indicates that each of the four was the result of an independent genetic event. New data suggest that vancomycin-intermediate S. aureus isolates, particularly those showing heteroresistance, are clinically significant. Finally, vancomycin-resistant enterococci continue to be reported from around the world. Novel infection control measures, however, may aid in reducing the spread of these organisms in healthcare settings. SUMMARY: The exchange of genetic information, particularly the vanA gene, between and among staphylococci and enterococci will continue to challenge physicians, microbiologists, and infection control practitioners in efforts to identify, treat, and prevent infections with these pathogens.

Enterococcus↗
PubMed2005

Comparison of Tn1546-like elements in vancomycin-resistant Staphylococcus aureus isolates from Michigan and Pennsylvania.

In 2002, the first two clinical isolates of vancomycin-resistant Staphylococcus aureus (VRSA) containing vanA were recovered in Michigan and Pennsylvania. Tn1546, a mobile genetic element that encodes high-level vancomycin resistance in enterococci, was present in both isolates. With PCR and DNA sequence analysis, we compared the Tn1546 elements from each isolate to the prototype Tn1546 element. The Michigan VRSA element was identical to the prototype Tn1546 element. The Pennsylvania VRSA element showed three distinct modifications: a deletion of nucleotides 1 to 3098 at the 5' end, which eliminated the orf1 region; an 809-bp IS1216V-like element inserted before nucleotide 3099 of Tn1546; and an inverted 1,499-bp IS1251-like element inserted into the vanSH intergenic region. These differences in the Tn1546-like elements indicate that the first two VRSA isolates were the result of independent genetic events.

DNA Transposable Elements↗
PubMed2005

Identification of a new allelic variant of the Acinetobacter baumannii cephalosporinase, ADC-7 beta-lactamase: defining a unique family of class C enzymes.

Acinetobacter spp. are emerging as opportunistic hospital pathogens that demonstrate resistance to many classes of antibiotics. In a metropolitan hospital in Cleveland, a clinical isolate of Acinetobacter baumannii that tested resistant to cefepime and ceftazidime (MIC = 32 microg/ml) was identified. Herein, we sought to determine the molecular basis for the extended-spectrum-cephalosporin resistance. Using analytical isoelectric focusing, a beta-lactamase with a pI of > or = 9.2 was detected. PCR amplification with specific A. baumannii cephalosporinase primers yielded a 1,152-bp product which, when sequenced, identified a novel 383-amino-acid class C enzyme. Expressed in Escherichia coli DH10B, this beta-lactamase demonstrated greater resistance against ceftazidime and cefotaxime than cefepime (4.0 microg/ml versus 0.06 microg/ml). The kinetic characteristics of this beta-lactamase were similar to other cephalosporinases found in Acinetobacter spp. In addition, this cephalosporinase was inhibited by meropenem, imipenem, ertapenem, and sulopenem (K(i) < 40 microM). The amino acid compositions of this novel enzyme and other class C beta-lactamases thus far described for A. baumannii, Acinetobacter genomic species 3, and Oligella urethralis in Europe and South Africa suggest that this cephalosporinase defines a unique family of class C enzymes. We propose a uniform designation for this family of cephalosporinases (Acinetobacter-derived cephalosporinases [ADC]) found in Acinetobacter spp. and identify this enzyme as ADC-7 beta-lactamase. The coalescence of Acinetobacter ampC beta-lactamases into a single common ancestor and the substantial phylogenetic distance separating them from other ampC genes support the logical value of developing a system of nomenclature for these Acinetobacter cephalosporinase genes.

Acinetobacter baumannii↗
PubMed2005

Testing for induction of clindamycin resistance in erythromycin-resistant isolates of Staphylococcus aureus.

Disk diffusion and broth microdilution (BMD) were used to perform clindamycin (CLI) induction testing on 128 selected nonduplicate isolates of Staphylococcus aureus. Disk diffusion testing involved placing CLI and erythromycin (ERY) disks approximately 12 mm apart (measured edge to edge) on a Mueller-Hinton agar plate that had been inoculated with an S. aureus isolate; the plate was then incubated for 16 to 18 h. Two distinct induction phenotypes (labeled D and D(+)) and four noninduction phenotypes (designated as negative [Neg], hazy D zone [HD], resistant [R], and susceptible [S]) were observed in disk diffusion results. A clear, D-shaped zone of inhibition around the CLI disk was designated as the D phenotype and was observed for 21 isolates while a D-shaped zone containing inner colonies growing up to the CLI disk was designated as D(+) (17 isolates). In addition, 10 isolates were CLI susceptible and ERY resistant but were not inducible and showed no blunting of the CLI zone (Neg phenotype). Isolates that were CLI and ERY resistant (constitutive macrolide-lincosamide-streptogramin B resistance) demonstrated either a double zone of inhibition with an inner ring of reduced growth up to the edge of the disks (HD phenotype; 33 isolates) or solid growth around the CLI and ERY disks (R phenotype; 16 isolates). Finally, 31 isolates were susceptible by disk testing to both CLI and ERY (S phenotype). PCR results showed that isolates with a D phenotype harbored ermA, isolates with a D(+) phenotype contained either ermC (16 isolates) or ermA and ermC (one isolate), and all 10 isolates with a Neg phenotype contained msrA. All isolates with an HD or R phenotype harbored at least one erm gene. Isolates showing the D(+) phenotype by disk diffusion were also detected by BMD using a variety of CLI and ERY concentrations; however, isolates with the D phenotype were more difficult to detect by BMD and will likely require optimization of ERY and CLI concentrations in multilaboratory studies to ensure adequate sensitivity. Thus, at present, disk diffusion is the preferred method for testing S. aureus isolates for inducible CLI resistance.

Anti-Bacterial Agents↗
PubMed2005

Selection of strains for quality assessment of the disk induction method for detection of inducible clindamycin resistance in Staphylococci: a CLSI collaborative study.

A nine-laboratory collaborative study was conducted to select positive and negative quality assessment control strains for the detection of inducible clindamycin resistance in staphylococci. Four strains of Staphylococcus aureus were tested as unknowns on 10 different days in each laboratory using the recently recommended CLSI (formerly NCCLS) disk diffusion method and the inoculum purity control method. Strains contained either macrolide-lincosamide-streptogramin B (MLSB) resistance genes encoded by erm(A) or erm(C) or a macrolide resistance efflux pump encoded by msr(A). Based upon the results of this study, strain UT 32 (now designated ATCC strain BAA-977) containing erm(A) is recommended as the positive control organism for inducible clindamycin resistance. Strain UT 25 (now designated ATCC BAA-976), which harbors the efflux pump encoded by msr(A), is recommended as the negative control organism.

Anti-Bacterial Agents↗
PubMed2005

Results of disk diffusion testing with cefoxitin correlate with presence of mecA in Staphylococcus spp.

The cefoxitin disk diffusion (DD) test for predicting mecA-mediated oxacillin resistance in staphylococci was assessed during a three-phase study. In phase 1, one laboratory tested 62 and 53 strains of Staphylococcus aureus and coagulase-negative staphylococci (CoNS), respectively. These data were used to choose the provisional cefoxitin DD breakpoints (resistant/susceptible) of < or =19 mm/> or =20 mm for S. aureus and < or =24 mm/> or =25 mm for CoNS for the next phase of testing. In phase 2, 10 laboratories each tested approximately 40 in-house strains of staphylococci (half of which were S. aureus) using Mueller-Hinton agar from different manufacturers. In this phase, the sensitivity and specificity, respectively, of the cefoxitin disk test were 98 and 100% for S. aureus and 99 and 96% for CoNS. The cefoxitin DD test performed equivalently to oxacillin broth microdilution (BMD) and to oxacillin DD tests among S. aureus and mecA-positive CoNS strains but gave better results than oxacillin BMD or oxacillin DD for mecA-negative strains of CoNS. The cefoxitin DD test also was much easier to read and did not require the use of transmitted light for detection of resistance. Based on data from the first two phases, the Clinical and Laboratory Standards Institute (CLSI; formerly NCCLS) adopted the use of the cefoxitin DD test for predicting mecA-mediated oxacillin resistance in staphylococci and revised Table 2C in CLSI document M100-S14 to reflect the change. In the third phase, an additional 61 challenge strains of CoNS for which the oxacillin MICs were 0.5 to 2 microg/ml were tested in a single laboratory to determine the effectiveness of the cefoxitin DD test for this group of borderline-resistant isolates. These data were used to refine the description of the test in CLSI document M100-S15. The cefoxitin DD test is preferred over the oxacillin DD test for predicting mecA-mediated oxacillin resistance in S. aureus and CoNS.

Bacterial Proteins↗
PubMed2004

Vancomycin-resistant Staphylococcus aureus in the absence of vancomycin exposure.

We report findings from our investigation of the world's second clinical isolate of vancomycin-resistant Staphylococcus aureus (VRSA). An elderly man was hospitalized with an infected chronic heel ulcer and osteomyelitis. Before hospital admission, he received multiple courses of antibiotic therapy but, notably, no vancomycin. Numerous cultures of ulcer specimens (performed on an outpatient basis) grew methicillin-resistant, vancomycin-susceptible S. aureus and vancomycin-resistant Enterococcus species. At admission, an additional culture of a specimen from the heel ulcer grew S. aureus that was identified as VRSA (minimal inhibitory concentration for vancomycin [by broth-microdilution], 32 microg/mL). Further evaluation confirmed the presence of the vanA gene mediating vancomycin resistance. To assess VRSA transmission, we performed a carriage study of 283 identified contacts and an environmental survey of the patient's home; no VRSA isolates were recovered. This case illustrates that recent exposure by patients to vancomycin is not necessary for development of vanA-containing VRSA. For clinical and public health reasons, it is essential that microbiology laboratories adequately test for vancomycin-resistance in S. aureus.

Aged↗
PubMed2004

Outbreak of Clostridium difficile infection in a long-term care facility: association with gatifloxacin use.

To determine the cause of an increase in the rate of Clostridium difficile-associated diarrhea (CDAD) in a long-term care facility (LTCF), we analyzed CDAD cases among LTCF patients from October 2001 through June 2002. CDAD cases were identified from review of all enzyme immunoassays positive for C. difficile toxin A. The increase coincided with a formulary change from levofloxacin to gatifloxacin. We performed a case-control study in which we randomly selected control subjects from 612 LTCF admissions during this period. Although we examined a variety of risk factors, logistic regression analysis only demonstrated associations between CDAD and use of clindamycin (P=.005) and gatifloxacin, the latter being associated with an increasing risk of CDAD with increasing duration of gatifloxacin therapy (P<.0001). We concluded that an outbreak of CDAD in an LTCF was associated with a formulary change from levofloxacin to gatifloxacin. The rate of CDAD in the LTCF decreased after a change back to levofloxacin.

Case-Control Studies↗
PubMed2004

Emergence of community-associated methicillin-resistant Staphylococcus aureus at a Memphis, Tennessee Children's Hospital.

BACKGROUND: An epidemiologic investigation was performed because of a perceived increase in infections caused by community-associated methicillin-resistant Staphylococcus aureus (MRSA) among children in the greater Memphis area. METHODS: We reviewed medical records of 289 children evaluated from January 2000 to June 2002 at a children's hospital. Clinical criteria were applied to classify MRSA isolates as community-associated (n=51) or health care-associated (n=138). The relatedness of 33 archived S. aureus isolates was evaluated using pulsed field gel electrophoresis (PFGE) of Sma I-digested genomic DNA; a common pulsed field type was defined as > or = 80 % similarity based on Dice coefficients. PFGE profiles were compared with those in a national database of MRSA isolates. RESULTS: During the first 18 study months, 46 of 122 MRSA isolates (38%) were community-associated; this proportion increased to 106 of 167 isolates (63%) during the last 12 study months (P <.0001). Community-associated isolates were recovered from normally sterile sites as frequently as were health care-associated isolates (16% versus 13%). PFGE revealed that 15 of 16 community-associated isolates shared a common pulsed field type (USA300) observed in community-associated MRSA infections elsewhere in the United States and characterized by staphylococcal cassette chromosome mec type IV, clindamycin susceptibility and erythromycin resistance mediated by an msr A-encoded macrolide efflux pump. CONCLUSIONS: Community-associated MRSA has emerged as a potentially invasive pathogen among children in the greater Memphis area, and this phenomenon is not explained by spread of nosocomial strains into the community.

Child↗
PubMed2004

Vancomycin-resistant Staphylococcus aureus isolate from a patient in Pennsylvania.

A vancomycin-resistant Staphylococcus aureus (VRSA) isolate was obtained from a patient in Pennsylvania in September 2002. Species identification was confirmed by standard biochemical tests and analysis of 16S ribosomal DNA, gyrA, and gyrB sequences; all of the results were consistent with the S. aureus identification. The MICs of a variety of antimicrobial agents were determined by broth microdilution and macrodilution methods following National Committee for Clinical Laboratory Standards (NCCLS) guidelines. The isolate was resistant to vancomycin (MIC = 32 micro g/ml), aminoglycosides, beta-lactams, fluoroquinolones, macrolides, and tetracycline, but it was susceptible to linezolid, minocycline, quinupristin-dalfopristin, rifampin, teicoplanin, and trimethoprim-sulfamethoxazole. The isolate, which was originally detected by using disk diffusion and a vancomycin agar screen plate, was vancomycin susceptible by automated susceptibility testing methods. Pulsed-field gel electrophoresis (PFGE) of SmaI-digested genomic DNA indicated that the isolate belonged to the USA100 lineage (also known as the New York/Japan clone), the most common staphylococcal PFGE type found in hospitals in the United States. The VRSA isolate contained two plasmids of 120 and 4 kb and was positive for mecA and vanA by PCR amplification. The vanA sequence was identical to the vanA sequence present in Tn1546. A DNA probe for vanA hybridized to the 120-kb plasmid. This is the second VRSA isolate reported in the United States.

Anti-Bacterial Agents↗
PubMed2004

Beta-lactamase gene expression in a penicillin-resistant Bacillus anthracis strain.

Expression of the bla1 and bla2 genes in an archetypal Bacillus anthracis strain is insufficient for penicillin resistance. In a penicillin-resistant clinical isolate, both genes are highly transcribed, but bla1 is the major contributor to high-level resistance to ampicillin. Differential expression of the bla genes is dependent upon strain background.

Bacillus anthracis↗
PubMed2004

Variety of beta-lactamases produced by amoxicillin-clavulanate-resistant Escherichia coli isolated in the northeastern United States.

This study analyzed the enzymatic basis and molecular epidemiology of amoxicillin-clavulanate-resistant Escherichia coli isolated by the microbiology laboratory of a United States tertiary care hospital. From October 1998 to December 1999, all E. coli isolates were screened for ampicillin-sulbactam resistance. Of 283 isolates that tested resistant to ampicillin-sulbactam, 69 unique patient isolates were also resistant to amoxicillin-clavulanate by disk diffusion testing (zone diameter </= 13 mm). These amoxicillin-clavulanate-resistant E. coli isolates underwent agar dilution testing, pulsed-field gel electrophoresis, PCR analysis, and isoelectric focusing. The mean age of study patients was 52 years; 78% were female. Among the isolates, 12 were nosocomial (rate of amoxicillin-clavulanate resistance = 4.7%) and 57 were community acquired (rate of amoxicillin-clavulanate resistance = 2.8%). No predominant strain was identified. By agar dilution testing, 67 isolates were nonsusceptible (39 resistant and 28 intermediate) to amoxicillin-clavulanate and 37 were piperacillin-tazobactam resistant but only 8 were ceftazidime resistant (ceftazidime MIC >/= 32 micro g/ml). Two isolates were susceptible to amoxicillin-clavulanic acid by agar dilution, although they were resistant by disk diffusion testing. The distribution of beta-lactamases was as follows: the TEM type alone was found in 52 isolates, the AmpC type was found in 4 isolates (2 identified as containing CMY-2), the TEM type and CMY-2 were found in 2 isolates, and the OXA type was found in 1 isolate. Also, there was one isolate with the TEM type and the SHV type and one with the TEM type and a second, unidentified enzyme. Among the isolates with TEM-type enzymes, two extended-spectrum beta-lactamase-producing isolates were identified but two isolates with inhibitor-resistant TEM (IRT) enzymes (one with TEM-34 [IRT-6] and the other with a novel enzyme [tentatively assigned the designation TEM-122]) were more interesting.

Adolescent↗
PubMed2004

Utility of NCCLS guidelines for identifying extended-spectrum beta-lactamases in non-Escherichia coli and Non-Klebsiella spp. of Enterobacteriaceae.

NCCLS screening and confirmation methods for detecting extended-spectrum beta-lactamases (ESBLs) apply only to Escherichia coli and Klebsiella spp., yet ESBLs have been found in other members of the family Enterobacteriaceae. We evaluated the effectiveness of NCCLS methods for detecting ESBLs in 690 gram-negative isolates of Enterobacteriaceae that excluded E. coli, Klebsiella pneumoniae, and Klebsiella oxytoca. Isolates were collected between January 1996 and June 1999 from 53 U.S. hospitals participating in Project ICARE (Intensive Care Antimicrobial Resistance Epidemiology). The antimicrobial susceptibility patterns of the isolates were determined by using the NCCLS broth microdilution method (BMD), and those isolates for which the MIC of ceftazidime, cefotaxime, ceftriaxone, or aztreonam was >or=2 microg/ml or the MIC of cefpodoxime was >or=8 microg/ml (positive ESBL screen test) were further tested for a clavulanic acid (CA) effect by BMD and the disk diffusion method (confirmation tests). Although 355 (51.4%) of the isolates were ESBL screen test positive, only 15 (2.2%) showed a CA effect. Since 3 of the 15 isolates were already highly resistant to the five NCCLS indicator drugs, ESBL detection would have an impact on the reporting of only 1.7% of the isolates in the study. Only 6 of the 15 isolates that showed a CA effect contained a bla(TEM), bla(SHV), bla(CTX-M), or bla(OXA) beta-lactamase gene as determined by PCR (with a corresponding isoelectric focusing pattern). Extension of the NCCLS guidelines for ESBL detection to Enterobacteriaceae other than E. coli and Klebsiella spp. does not appear to be warranted in the United States at present, since the test has poor specificity for this population and would result in changes in categorical interpretations for only 1.7% of Enterobacteriaceae tested.

Diffusion↗
PubMed2004

Antimicrobial susceptibility testing of Acinetobacter spp. by NCCLS broth microdilution and disk diffusion methods.

Although both broth microdilution (BMD) and disk diffusion (DD) are listed by NCCLS as acceptable methods for testing Acinetobacter spp. for antimicrobial susceptibility, few studies have compared the results generated by the two methods. We tested 196 isolates of Acinetobacter spp. from nine U.S. hospitals and from the Centers for Disease Control culture collection by using BMD and DD and clinically appropriate antimicrobial agents. Categorical results for amikacin, ciprofloxacin, gatifloxacin, gentamicin, imipenem, levofloxacin, meropenem, tobramycin, and trimethoprim-sulfamethoxazole were comparable for the two methods: there was only one very major (VM) error, with tobramycin, and only one major (M) error, with meropenem, when DD results were compared with BMD results. However, VM errors were frequent with the beta-lactams and beta-lactam-beta-lactam inhibitor combinations, while M errors were often observed with tetracyclines. For BMD, tests frequently exhibited subtle growth patterns that were difficult to interpret, especially for beta-lactams. If subtle growth (i.e., granular, small button, or "starry" growth) was considered positive, error rates between BMD and DD were unacceptably high for ampicillin-sulbactam (VM error, 9.8%; minor [m] error, 16.1%), piperacillin (VM error, 5.7%; m error, 13.5%), piperacillin-tazobactam (VM error, 9.3%; m error, 12.9%), ceftazidime (VM error, 6.2%; m error, 11.4%), cefepime (VM error, 6.2%; m error, 13.0%), cefotaxime (m error, 21.2%), ceftriaxone (m error, 23.3%), tetracycline (M error, 11.4%; m error, 32.1%), and doxycycline (M error, 2.6%). When subtle growth patterns were ignored, the agreement still did not achieve acceptable levels. To determine if the problems with BMD testing occurred in other laboratories, we sent frozen BMD panels containing beta-lactam drugs and nine isolates to six labs with experience in performing BMD and DD. Among these laboratories, cefepime MICs ranged from < or =8 to > or =32 microg/ml for four of the nine strains, confirming the problem in interpreting BMD results. Discrepancies between the categorical interpretations of BMD and DD tests were noted primarily with cefepime and piperacillin, for which the BMD results were typically more resistant. Clinical laboratories should be aware of these discrepancies. At present, there are no data to indicate which method provides more clinically relevant information.

Acinetobacter↗
PubMed2004

Accuracy and appropriateness of antimicrobial susceptibility test reporting for bacteria isolated from blood cultures.

Accurate antimicrobial susceptibility testing (AST) and appropriate reporting of AST results for pathogens isolated from blood cultures are critical functions of the microbiology laboratory. We studied AST performance and reporting from positive blood cultures at hospital microbiology laboratories in Iowa. One hundred sixteen episodes of bacteremia from 14 participating hospitals were examined. We detected AST or identification errors for 18 episodes (16%) and judged reporting of AST results to be inappropriate for 38 episodes (33%). Further study is necessary to determine the impact of testing errors and suboptimal reporting of results on the management of bloodstream infection.

Bacteremia↗