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Biomedical subjects

F W Goldstein

Publications and source records attributed to F W Goldstein.

At least 19 recordsLinked to original sources

Monitoring of vancomycin serum levels for the treatment of staphylococcal infections.

Vancomycin serum concentrations were determined for 1,737 patients treated with either 2 x 1 g of vancomycin or 4 x 500 mg daily (780 patients), according to current nomograms, or by continuous infusion (957 patients) with a loading dose (1 g) and a total of 2-6 g daily. Trough serum concentrations were determined after 36-48 h. Adequate serum levels for the treatment of a normal methicillin-resistant Staphylococcus aureus (MRSA) and a glycopeptide-intermediate S. aureus (GISA) were observed in 81% and 20.9% of patients, respectively. The data support theoretical arguments that higher and more sustained serum levels of vancomycin, obtained by continuous infusion, may enhance clinical efficacy.

Anti-Bacterial Agents↗

European Committee on Antimicrobial Susceptibility Testing (EUCAST) Technical Notes on antimicrobial susceptibility testing.

The main objectives of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are to harmonise breakpoints for antimicrobial agents in Europe, and to act as the breakpoint committee for the European Medicines Agency (EMEA) during the registration of new antimicrobial agents. Detailed EUCAST procedures for harmonising and setting breakpoints for antimicrobial agents are available on the EUCAST website. Beginning with the current issue, a series of EUCAST Technical Notes will be published in CMI, based on the rationale documents produced by EUCAST for each of the antimicrobial agents studied, with the aim of highlighting important background information underlying decisions on breakpoints made by EUCAST.

Advisory Committees↗

False synergy between vancomycin and beta-lactams against glycopeptide-intermediate Staphylococcus aureus (GISA) caused by inappropriate testing methods.

The combination of vancomycin and beta-lactams is often considered synergistic and has been recommended for the treatment of glycopeptide-intermediate Staphylococcus aureus (GISA) infections. In this study, the combination of vancomycin or teicoplanin with different beta-lactams was tested. When using NaCl 4% w/v, for better expression of heterogeneous resistance to beta-lactams, with a longer (48-h) incubation period and a higher (10(7) CFU/mL) inoculum, the association of vancomycin with beta-lactams was antagonistic. However, a synergistic effect was observed for teicoplanin under the same conditions.

Anti-Bacterial Agents↗

Vancomycin-resistant Staphylococcus aureus: no apocalypse now.

The number of reports concerning vancomycin-resistant Staphylococcus aureus is much higher than the number of true resistant strains or unexpected clinical failures. Many confounding factors, including inadequate serum levels, severely ill patients, foreign devices or undrained abscesses, are more likely to be responsible for the clinical failures than resistance to vancomycin.

Drug Therapy, Combination↗

OXA-35 is an OXA-10-related beta-lactamase from Pseudomonas aeruginosa.

Pseudomonas aeruginosa clinical isolate PA35 is resistant to amino- and ureido-penicillins, has intermediate susceptibility to cefsulodin, cefepime and aztreonam, and is susceptible to imipenem and ceftazidime. Cloning and sequencing revealed a new beta-lactamase variant, OXA-35, sharing 96% amino acid identity with OXA-10. OXA-35 displays a restricted-substrate hydrolysis profile with improved hydrolysis of amoxicillin and cloxacillin compared with OXA-10. OXA-35 differs from derivatives OXA-19 and OXA-28 by one amino acid substitution and may be a progenitor of these OXA-13-like extended-spectrum beta-lactamases.

Aged↗

Antibiotic susceptibility of bacterial strains isolated from patients with community-acquired urinary tract infections in France. Multicentre Study Group.

The aim of this study was to determine the distribution and antibiotic susceptibility patterns of bacterial strains isolated from adults with community-acquired urinary tract infections (UTI) in France. From December 1996 to March 1997, each of 15 private laboratories in France consecutively collected about 80 non-duplicate strains isolated from adult outpatients with UTI, including patients receiving care at home, and tested their susceptibility by the disk diffusion test. A total of 1160 strains were collected: 1031 gram-negative bacilli, including Escherichia coli (n = 865), Proteus mirabilis (n = 68) and Klebsiella spp. (n = 40), and 129 gram-positive cocci, including Staphylococcus aureus (n = 16), other staphylococci (n = 25), group B streptococci (n = 25) and enterococci (n = 63). In the case of 430 bacterial isolates, the patients had either been hospitalised in the last 6 months or received antibiotic treatment in the last 3 months. The antibiotic susceptibility rates for Escherichia coli were: amoxicillin (58.7%), amoxicillin-clavulanic acid (63.3%), ticarcillin (61.4%), cephalothin (66.8%) cefuroxime (77.6%), cefixime (83.6%), cefotaxime (99.8%), ceftazidime (99%), nalidixic acid (91.9%), norfloxacin (96.6%), ofloxacin (96.3%), ciprofloxacin (98.3%), cotrimoxazole (78.2%), fosfomycin (99.1%) and gentamicin (98.4%). Of the Enterobacteriaceae, five strains produced an extended-spectrum beta-lactamase. Methicillin resistance was detected in nine Staphylococcus aureus isolates. The most important findings were two extended-spectrum, beta-lactamase-producing and three methicillin-resistant Staphylococcus aureus strains isolated from patients who had not been hospitalised in the last 6 months or taken antibiotics in the last 3 months. The findings indicate that these strains can spread within the community; therefore, monitoring antibiotic susceptibility of bacteria isolated in the community appears to be mandatory.

Adolescent↗

In-vitro activity of levofloxacin, a new fluoroquinolone: evaluation against Haemophilus influenzae and Moraxella catarrhalis.

The in-vitro activity of levofloxacin was studied against 10 beta-lactamase-negative and 93 beta-lactamase-positive Moraxella catarrhalis isolates, and 65 beta-lactamase-negative and 35 beta-lactamase-positive Haemophilus influenzae isolates. The MICs of levofloxacin were determined by agar dilution on Mueller-Hinton agar (with the addition of 5% horse blood for M. catarrhalis) or on Haemophilus Test Medium for H. influenzae, and were compared with those of ofloxacin, ciprofloxacin and sparfloxacin, as well as pefloxacin and D-ofloxacin for M. catarrhalis. The fluoroquinolones showed similar activity against isolates of H. influenzae and M. catarrhalis, irrespective of beta-lactamase production. Levofloxacin (MIC50/90 0.06 mg/L) was 64 times more active against M. catarrhalis than D-ofloxacin (MIC50/90 4/8 mg/L) and twice as active as ofloxacin (MIC50/90 0.125 mg/L). Ciprofloxacin had an MIC50/90 of 0.03/0.06 mg/L and sparfloxacin showed an MIC50/90 of 0.015 mg/L against M. catarrhalis irrespective of the resistance phenotype of the isolates. Against H. influenzae, levofloxacin was twice as active as ofloxacin (MIC90 values 0.03 mg/L versus 0.06 mg/L), while the MIC90s of ciprofloxacin and sparfloxacin were both 0.015 mg/L. Our results therefore suggest that levofloxacin has potential for treating respiratory tract infections caused by H. influenzae and M. catarrhalis.

Anti-Infective Agents↗

Low rate of Clostridium difficile colonization in ambulatory and hospitalized HIV-infected patients in a hospital unit: a prospective survey.

OBJECTIVE: To determine the frequency of Clostridium difficile carriage in HIV-infected in- and out-patients, and to assess the role of this carriage in nosocomial transmission of C. difficile. PATIENTS AND METHODS: Prospective study in a university hospital. Forty-five consecutive HIV-infected out-patients and 120 hospitalized patients (52 HIV and 68 non HIV-infected-patients) were studied. During the period of hospitalization, 44 patients (24 HIV and 20 non-HIV-infected patients) with a negative culture within 48 h of admission were followed weekly for fecal carriage. Clostridium difficile culture and latex agglutination were performed on the fecal samples of each patient. In the case of positive culture and/or latex agglutination, C. difficile toxin assays were performed by microtitre cytotoxicity method. RESULTS: Out-patients: one patient was a carrier and one patient with diarrhoea was infected with a toxigenic strain (2/45, 4.5%, 95% CI = 1-17). Eighty percent of the HIV-infected out-patients had received antimicrobial agents previously. In-patients: in the first 48 h, five asymptomatic patients were carriers (three non-HIV and two HIV-infected patients). Among 20 patients who complained of diarrhoea, one HIV-infected patient had only a positive latex agglutination and one HIV-infected patient was infected with a toxigenic strain. Overall, 7/120 (5.8%, 95% CI = 2-10) patients were infected or colonized with C. difficile. During the hospitalization (743 patient-days), none of the 44 patients acquired C. difficile. CONCLUSION: This study suggests that in this given unit, C. difficile carriage is low, at least with single room accommodation, and in the absence of clusters of cases. This carriage is not different in HIV and non-HIV infected patients despite treatment with multiple antibiotics, and is not different in patients managed in different care environments. The systematic identification of C. difficile carriers for isolation and prophylactic treatment is not useful under these circumstances.

Ambulatory Care↗

Consequences of increasing resistance to antimicrobial agents.

The correlation between in vitro bacterial susceptibility results and clinical outcome has been debated for many years. Bacterial resistance traits are more significantly correlated with failure of therapy than is an organism's susceptibility to an antimicrobial agent. We review the situations that have supported the clinical relevance of in vitro bacterial resistance. Those situations include: emergence, during therapy, of a new resistance marker not known before; selection of a resistant mutant or acquisition of a resistance gene during therapy; failure to recognize or take into account a new resistance mechanism; and superinfection with resistant bacteria. More information should be obtained in the future by performing studies oriented toward bacteriologically documented clinical failures and by better communication between microbiologists and physicians to correlate the in vitro data with host status, the pharmacokinetics of the antimicrobial agent, and the bacteriologic and clinical outcome.

Bacterial Infections↗

Carbapenems as inhibitors of OXA-13, a novel, integron-encoded beta-lactamase in Pseudomonas aeruginosa.

A clinical Pseudomonas aeruginosa strain, PAe391, was found to be resistant to a number of antibiotics including ticarcillin, piperacillin, cefsulodin and amikacin, and a disk diffusion assay showed evidence of pronounced synergy between imipenem and various beta-lactam antibiotics. Cloning and nucleotide sequence analysis revealed the dicistronic arrangement of an aac(6')-Ib variant and a novel blaOXA-type gene between the intI and qacE delta 1 genes typical of integrons, in PAe391, this integron was apparently chromosome-borne. The beta-lactamase, named OXA-13, displayed nine amino acid changes with respect to OXA-10:I in position 10 of OXA-10 to T (I10T), G20S, D55N, N73S, T107S, Y174F, E229G, S245N and E259A, OXA-13 (pIapp = 8.0) showed poor catalytic activity against penicillins as well as cephalosporins, but was efficient in hydrolysing some penicillinase-resistant beta-lactams, such as cefotaxime and aztreonam. It was efficiently inhibited by imipenem (KIapp = 11 nM), and formed a stable complex. While the KIapp value of meropenem was similar (16 nM), the corresponding complex was less stable.

Anti-Bacterial Agents↗