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Howard S Gold

Publications and source records attributed to Howard S Gold.

At least 19 recordsLinked to original sources
PubMed2006

Effects of prolonged vancomycin administration on methicillin-resistant Staphylococcus aureus (MRSA) in a patient with recurrent bacteraemia.

OBJECTIVES: To evaluate microbiological properties of methicillin-resistant Staphylococcus aureus (MRSA) during prolonged vancomycin therapy. METHODS: We evaluated vancomycin susceptibility and heteroresistance, accessory gene regulator (agr) function, autolysis, biofilm production and in vitro vancomycin killing in serial MRSA bloodstream isolates obtained over a 30 month period from a patient with a chronic endovascular infection. RESULTS: Despite the fact that the MRSA in this patient had the same genetic background as other clinical glycopeptide intermediate-resistant S. aureus (GISA) isolates, vancomycin administered for 9 months, maintaining serum concentrations >10 mg/L, did not select for GISA. Minimal changes in vancomycin susceptibility were detected using agar dilution and population analysis methods. We noted increases in delta haemolysin production, autolysis and the bactericidal effects of vancomycin in vitro against the MRSA obtained after prolonged vancomycin suppressive therapy was discontinued. CONCLUSIONS: Despite the lack of development of detectable resistance, MRSA exposed to vancomycin for prolonged periods may begin to develop vancomycin tolerance and decreased autolysis. In addition, suppression of agr function appears to end after vancomycin is stopped. Whether these changes are prerequisites for attenuated vancomycin efficacy and the development of glycopeptide resistance warrants further study. The development of vancomycin resistance may be more difficult under conditions where vancomycin serum concentrations are maintained >10 mg/L.

Anti-Bacterial Agents↗
PubMed2006

Emergence of a clinical daptomycin-resistant Staphylococcus aureus isolate during treatment of methicillin-resistant Staphylococcus aureus bacteremia and osteomyelitis.

The emergence of a clinically daptomycin-resistant Staphylococcus aureus isolate occurred during treatment of methicillin-resistant S. aureus bacteremia and probable vertebral osteomyelitis. The breakthrough isolate was indistinguishable from pretreatment daptomycin-susceptible isolates by pulsed-field gel electrophoresis. Daptomycin nonsusceptibility was confirmed by MIC and time-kill curve analyses.

Anti-Bacterial Agents↗
PubMed2005

Extended-spectrum beta-lactamases among Enterobacter isolates obtained in Tel Aviv, Israel.

The extended-spectrum beta-lactamase (ESBL)-producing phenotype is frequent among Enterobacter isolates at the Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. We examined the clonal relatedness and characterized the ESBLs of a collection of these strains. Clonal relatedness was determined by pulsed-field gel electrophoresis. Isoelectric focusing (IEF) and transconjugation experiments were performed. ESBL gene families were screened by colony hybridization and PCR for bla(TEM), bla(SHV), bla(CTX-M), bla(IBC), bla(PER), bla(OXA), bla(VEB), and bla(SFO); and the PCR products were sequenced. The 17 Enterobacter isolates studied comprised 15 distinct genotypes. All isolates showed at least one IEF band (range, one to five bands) whose appearance was suppressed by addition of clavulanate; pIs ranged from 5.4 to > or = 8.2. Colony hybridization identified at least one family of beta-lactamase genes in 11 isolates: 10 harbored bla(TEM) and 9 harbored bla(SHV). PCR screening and sequence analysis of the PCR products for bla(TEM), bla(SHV), and bla(CTX-M) identified TEM-1 in 11 isolates, SHV-12 in 7 isolates, SHV-1 in 1 isolate, a CTX-M-2-like gene in 2 isolates, and CTX-M-26 in 1 isolate. In transconjugation experiments with four isolates harboring bla(TEM-1) and bla(SHV-12), both genes were simultaneously transferred to the recipient strain Escherichia coli HB101. Plasmid mapping, PCR, and Southern analysis with TEM- and SHV-specific probes demonstrated that a single transferred plasmid carried both the TEM-1 and the SHV-12 genes. The widespread presence of ESBLs among Enterobacter isolates in Tel Aviv is likely due not to clonal spread but, rather, to plasmid-mediated transfer, at times simultaneously, of genes encoding several types of enzymes. The dominant ESBL identified was SHV-12.

Anti-Bacterial Agents↗
PubMed2004

Antimicrobial resistance to linezolid.

Acquired resistance to linezolid, the first approved oxazolidinone, has been selected in laboratory experiments and has been observed in clinical isolates of gram-positive cocci. This resistance has typically been associated with single-nucleotide changes in varying numbers of copies of the genes encoding 23S ribosomal RNA. In the current environment of increasingly prevalent resistance to standard antibiotics, linezolid is an important drug because of its activity against a number of clinically significant gram-positive cocci, including multidrug-resistant staphylococci and enterococci. Although resistance to linezolid remains uncommon, the development of resistance by clinical isolates should prompt increased attention to susceptibility testing for this agent and should be taken into account in consideration of the therapeutic use of this drug.

Acetamides↗
PubMed2004

Reversion to susceptibility in a linezolid-resistant clinical isolate of Staphylococcus aureus.

OBJECTIVES: Linezolid resistance in rare isolates of Staphylococcus aureus has been associated with G2576T mutations in domain V of the 23S rRNA gene. We report the analysis of a clinical S. aureus isolate that developed linezolid resistance (MIC of linezolid of 12 mg/L) after a 25 day course of the drug. Sequencing identified G2576T mutations in four of the five copies of the 23S rRNA gene. METHODS: To examine the stability of this resistance, we serially passaged this original isolate 60 times over a 75 day period on antimicrobial-free medium. RESULTS: After 30 passages, the MIC of linezolid had decreased to 8 mg/L and only two of the five copies of the 23S rRNA gene contained the G2576T mutation. After 60 passages, the MIC of linezolid fell to 2 mg/L and only one of the five 23S rRNA gene copies contained the mutation. The original and two passaged staphylococci were indistinguishable by pulsed-field gel electrophoresis. CONCLUSIONS: In the absence of antibiotic pressure, linezolid resistance was unstable in a clinical isolate that did not have all copies of the 23S rRNA gene mutated, although a single copy of mutant rDNA was maintained. Gene conversion was probably the mechanism for this reversion, using the wild-type 23S rRNA gene sequences to replace the G2576T mutation by homologous recombination.

Acetamides↗
PubMed2004

Linezolid resistance in sequential Staphylococcus aureus isolates associated with a T2500A mutation in the 23S rRNA gene and loss of a single copy of rRNA.

Linezolid is an important therapeutic option for infections caused by resistant gram-positive bacteria. We report the characterization of sequential methicillin-resistant Staphylococcus aureus (MRSA) bloodstream isolates that developed resistance in a patient treated with a prolonged course of linezolid. Analysis of this series of clinical MRSA isolates detected, in the resistant isolates, the presence of a T2500A mutation in the domain V region of the 23S rRNA gene. In addition, the loss of a single copy of the 23S rRNA gene was found in 2 of the resistant isolates. As a result of these 2 factors, the proportion of mutant : wild-type 23S rRNA genes increased in association with an increase in the minimum inhibitory concentration of linezolid. The most recent isolate of this series was recovered 7 months after the patient discontinued linezolid and demonstrated reversion to a susceptible phenotype associated with a loss of the T2500A mutation.

Acetamides↗
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

The magnitude of the association between fluoroquinolone use and quinolone-resistant Escherichia coli and Klebsiella pneumoniae may be lower than previously reported.

Case-control analyses of resistant versus susceptible isolates have implicated fluoroquinolone exposure as a strong risk factor for fluoroquinolone-resistant isolates of Enterobacteriaceae. We suspect that such methodology may overestimate this association. A total of 84 cases with fluoroquinolone-resistant isolates and 578 cases with fluoroquinolone-susceptible isolates of Escherichia coli or Klebsiella pneumoniae were compared with 608 hospitalized controls in parallel multivariable analyses. For comparison of previous estimates, the results of 10 published case-control studies of risk for fluoroquinolone resistance in isolates of Enterobacteriaceae were pooled by using a random-effects model. Exposure to fluoroquinolones was significantly positively associated with fluoroquinolone resistance (odds ratio [OR], 3.17) and negatively associated with fluoroquinolone susceptibility (OR, 0.18). Multivariable analyses yielded similar estimates (ORs, 2.04 and 0.10, respectively). As data on antibiotic exposure were limited to inpatient prescriptions, misclassification of fluoroquinolone exposure in persons who received fluoroquinolones as outpatients may have led to an underestimation of the true effect size. Pooling the results of previously published studies in which a direct comparison of fluoroquinolone-resistant and fluoroquinolone-susceptible cases was used resulted in a markedly higher effect estimate (OR, 18.7). Had we directly compared resistant and susceptible cases, our univariate OR for the association between fluoroquinolone use and the isolation of resistant Enterobacteriaceae would have been 19.3, and the multivariate OR would have been 16.5. Fluoroquinolone use is significantly associated with the isolation of fluoroquinolone-resistant Enterobacteriaceae; however, previous studies likely exaggerated the magnitude of this association.

Aged↗
PubMed2004

Linezolid-resistant Enterococcus faecalis isolated from a cord blood transplant recipient.

We report a linezolid-resistant Enterococcus faecalis infection in a cord blood stem cell transplant recipient previously treated with linezolid for bloodstream infections by vancomycin-resistant enterococci. Sequencing showed a G2576U mutation in the 23S rRNA gene. Because of the important niche of linezolid in cancer treatment, linezolid-resistant E. faecalis is noteworthy.

Acetamides↗
PubMed2004

Fluoroquinolones protective against cephalosporin resistance in gram-negative nosocomial pathogens.

In a matched case-control study, we studied the effect of prior receipt of fluoroquinolones on isolation of three third-generation cephalosporin-resistant gram-negative nosocomial pathogens. Two hundred eighty-two cases with a third-generation cephalosporin-resistant pathogen (203 with Enterobacter spp., 50 with Pseudomonas aeruginosa, and 29 with Klebsiella pneumoniae) were matched on length of stay to controls in a 1:2 ratio. Case-patients and controls were similar in age (mean 62 years) and sex (54% male). Variables predicting third-generation cephalosporin resistance were surgery (p = 0.005); intensive care unit stay (p < 0.001); and receipt of a b-lactam/b-lactamase inhibitor (p < 0.001), a ureidopenicillin (p = 0.002), or a third-generation cephalosporin (p < 0.001). Receipt of a fluoroquinolone was protective against isolation of a third-generation cephalosporin-resistant pathogen (p = 0.005). Interventional studies are required to determine whether replacing third-generation cephalosporins with fluoroquinolones will be effective in reducing cephalosporin resistance and the effect of such interventions on fluoroquinolone resistance.

Case-Control Studies↗
PubMed2003

Linezolid-resistant, vancomycin-resistant Enterococcus faecium infection in patients without prior exposure to linezolid.

We describe 2 patients without prior exposure to linezolid who were infected with closely related strains of linezolid- and vancomycin-resistant Enterococcus faecium (LRVREF) that may have been hospital acquired. Polymerase chain reaction amplification of the domain V region of the 23S ribosomal RNA gene demonstrated the presence of the G2576U mutation previously reported to be associated with linezolid resistance. Nosocomial transmission of LRVREF is an ominous sign and underscores the importance of meticulous infection-control measures.

Acetamides↗
PubMed2003

Staphylococcus aureus accessory gene regulator (agr) group II: is there a relationship to the development of intermediate-level glycopeptide resistance?

We previously determined that all 6 Staphylococcus aureus strains with confirmed intermediate-level resistance to glycopeptides (glycopeptide intermediate S. aureus [GISA]) from the United States that we tested belonged to accessory gene regulator (agr) group II. In the present study, we found that 56% of surveyed bloodstream methicillin-resistant S. aureus isolates (n = 148) at our hospital were agr group II, whereas only 24% of methicillin-susceptible S. aureus isolates (n = 33) were agr group II (P = .001). Population analysis of genetically engineered agr-null and parent wild-type strains of groups I, II, and IV revealed that, when agr function is lost, the agr group II knockout S. aureus was most likely to develop glycopeptide heteroresistance after growth in 1 microg/mL but not 16 microg/mL vancomycin. This strain was unique in showing decreased autolysis after growth in these conditions. This study suggests that some S. aureus strains have an intrinsic survival advantage under a glycopeptide selective pressure, which is possibly related to reduced autolysis after exposure to subinhibitory concentrations of glycopeptide.

Anti-Bacterial Agents↗
PubMed2003

Detection of Staphylococcus aureus in peripheral blood stem cell cultures after sterilization of standard blood cultures.

We report central venous catheter (CVC)-associated Staphylococcus aureus bacteremia detected by apheresis product culture after sterilization of standard blood cultures. A 64-year-old man with non-Hodgkin's lymphoma underwent peripheral blood stem cell (PBSC) collection. Five days after placement of a CVC, inflammation was evident at the insertion site. The CVC was removed and cephalexin was begun. Discharge at the site contained neutrophils and gram-positive cocci in pairs and clusters. Cultures of the discharge, of blood drawn via the CVC, of the CVC tip and of the apheresis product collected that day grew methicillin-susceptible S. aureus (MSSA). Cephalexin was discontinued in favor of oxacillin. Three days after removal of the CVC, PBSC collections were resumed via a contralateral CVC. Three sets of standard blood cultures drawn the day the new CVC was placed and the following day were negative, yet apheresis product cultures from each of these days grew MSSA. PBSC collections were halted, the CVC was removed, and oxacillin was continued via a peripherally inserted central catheter. Transesophageal echocardiography after two weeks of therapy revealed thickened mitral leaflets and damage to the posterior leaflet. Transthoracic echocardiography 11 weeks preceding this study had demonstrated normal mitral valve anatomy and function. Oxacillin was continued for six weeks, after which PBSC collections were resumed. Pulsed-field gel electrophoresis of the MSSA isolates revealed a clonal pattern. Cultures of apheresis product may be more sensitive to the presence of bacteremia than standard blood cultures, and they should guide clinical decisions when the bacteria isolated are potential pathogens or suggest clinical infection.

Blood Cells↗
PubMed2003

Enterococcus: an emerging pathogen in hospitals.

Enterococci remain an important cause of nosocomial infection, particularly among the critically ill. Nationwide, the incidence of enterococcal infections is rising, with an increasing proportion caused by resistant organisms. The spread of vancomycin-resistant enterococci (VRE) within hospitals has been well studied and helps to explain the proliferation of enterococcal disease. After hospital admission of an individual carrying VRE, persistent colonization contributes to the development of a reservoir of colonized inpatients. VRE is usually spread patient to patient by health care workers caring for colonized individuals. To interrupt this phenomenon, infection control efforts including improved hand hygiene, use of gloves and cover gowns, and antibiotic control measures have been promoted. Prospective data concerning the relative benefit of each intervention are limited, and no consensus has emerged regarding the optimal strategy for limiting the dissemination of VRE. Appropriate treatment of an individual patient infected with VRE depends upon successful interpretation of the antibiotic susceptibility profile of the infecting strain. For the critically ill patient, an aggressive approach to diagnosis and therapy is essential. However, even the newest agents available to treat resistant enterococci are limited because of emerging resistance and toxicity.

Journal Article↗
PubMed2003

Treatment with a broad-spectrum cephalosporin versus piperacillin-tazobactam and the risk for isolation of broad-spectrum cephalosporin-resistant Enterobacter species.

Receipt of a broad-spectrum cephalosporin is a strong risk factor for isolation of broad-spectrum cephalosporin-resistant Enterobacter species, and yet the risk from other broad-spectrum beta-lactams hydrolyzed by group 1 beta-lactamases has not been well characterized. We compared the risk conferred by broad-spectrum cephalosporins to that conferred by piperacillin-tazobactam, alone or in combination with an aminoglycoside or a fluoroquinolone. A retrospective cohort was monitored from treatment onset until a broad-spectrum cephalosporin-resistant Enterobacter strain was isolated or the patient was discharged. There were 447 patients in the piperacillin-tazobactam group and 2,341 patients in the broad-spectrum cephalosporin group. Groups were similar in age (mean, 62.5 years). The piperacillin-tazobactam group had a smaller percentage of men (32% versus 44%, P < 0.001) and a lower rate of intensive care unit stay (25% versus 38%, P < 0.001) but a higher rate of surgery (41% versus 26%, P < 0.001). Groups differed in the distribution of comorbidities. Resistant Enterobacter strains were isolated from 62 patients, 2% in each group (hazard ratio [RR] = 1.02 [P = 0.95]). In multivariable analysis, risk was similar among treatment groups (RR = 0.71 [P = 0.32]). Intensive care unit stay and surgery were associated with increased risk (RR = 4.53 [P < 0.001] and RR = 1.97 [P = 0.015], respectively), fluoroquinolones were protective (RR = 0.24 [P = 0.003]), and aminoglycosides did not affect risk (RR = 0.98 [P = 0.95]). The protective effect of fluoroquinolones against isolation of broad-spectrum cephalosporin-resistant Enterobacter spp. and the equivalence in risk associated with piperacillin-tazobactam and broad-spectrum cephalosporins may have important clinical and epidemiologic implications.

Anti-Bacterial Agents↗
PubMed2003

Clinical implications of varying degrees of vancomycin susceptibility in methicillin-resistant Staphylococcus aureus bacteremia.

We conducted a retrospective study of the clinical aspects of bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA) with heterogeneously reduced susceptibility to vancomycin. Bloodstream MRSA isolates were screened for reduced susceptibility by using brain-heart infusion agar, including 4 mg/L vancomycin with and without 4% NaCl. Patients whose isolates exhibited growth (case-patients) were compared with those whose isolates did not (controls) for demographics, coexisting chronic conditions, hospital events, antibiotic exposures, and outcomes. Sixty-one (41%) of 149 isolates exhibited growth. Subclones from 46 (75%) of these had a higher MIC of vancomycin than did their parent isolates. No isolates met criteria for vancomycin heteroresistance. No differences in potential predictors or in outcomes were found between case-patients and controls. These data show that patients with vancomycin-susceptible MRSA bacteremia have similar baseline clinical features and outcomes whether or not their bacterial isolates exhibit growth on screening media containing vancomycin.

Bacteremia↗
PubMed2003

Fluoroquinolones and the risk for methicillin-resistant Staphylococcus aureus in hospitalized patients.

To determine whether fluoroquinolone exposure is a risk factor for the isolation of Staphylococcus aureus and whether the effect is different for methicillin-resistant S. aureus (MRSA) versus methicillin--susceptible S. aureus (MSSA), we studied two case groups. The first case group included 222 patients with nosocomially acquired MRSA. The second case group included 163 patients with nosocomially acquired MSSA. A total of 343 patients admitted concurrently served as controls. Outcome measures were the adjusted odds ratio (OR) for isolation of MRSA and MSSA after fluoroquinolone exposure. Exposure to both levofloxacin (OR 5.4; p <0.0001) and ciprofloxacin (OR 2.2; p < 0.003) was associated with isolation of MRSA but not MSSA. After adjustment for multiple variables, both drugs remained risk factors for MRSA (levofloxacin OR 3.4; p <0.0001; ciprofloxacin OR 2.5; p = 0.005) but not MSSA. Exposure to levofloxacin or ciprofloxacin is a significant risk factor for the isolation of MRSA, but not MSSA.

Aged↗