Paul C. Schreckenberger

Infections due to vancomycin-resistant Enterococcus faecium resistant to linezolid

Linezolid is a new oxazolidinone antibiotic used to treat infections caused by vancomycin-resistant enterococci (VRE). In early clinical trials, emergence of resistance occurred rarely. We report clinical details and antibiotic susceptibility from five patients treated with linezolid for VRE infections who had resistant organisms isolated during therapy. Four were transplant patients receiving protracted courses of the drug; three cases were associated with treatment failure. One of 45 linezolid-treated patients developed resistance during therapy. Susceptibility testing should be done in all cases on starting therapy.

Streptococcus milleri group: renewed interest in an elusive pathogen.

The following review examines the bacteriological characteristics, epidemiology, pathogenicity and antimicrobial susceptibility of the “Streptococcus milleri group”. “Streptococcus milleri group” is a term for a large group of streptococci which includesStreptococcus intermedius, Streptococcus constellatus andStreptococcus anginosus. Usually considered commensals, these organisms are often associated with various pyogenic infections including cardiac, abdominal, skin and central nervous system infections. Organisms of the “Streptococcus milleri group” are often unrecognized pathogens due to the lack of uniformity in classifications and difficulties in microbiological identification. Penicillin G, cephalosporins, clindamycin and vancomycin all possess activity against these streptococci. Use of agents with poor activity may promote infections with “Streptococcus milleri group” and allow it to exhibit its pathogenicity. An understanding of these organisms may aid in their recognition and proper treatment.

Risk Factors Associated with the Development of Infection with Linezolid- and Vancomycin-Resistant Enterococcus faecium

This retrospective cohort study revealed that linezolid resistance in vancomycin-resistant Enterococcus faecium was dependent on prior linezolid exposure and duration of linezolid therapy. These strains of E. faecium were resistant to the entire class of oxazolidinones.

Broad Resistance Due to Plasmid-Mediated AmpC β-Lactamases in Clinical Isolates of Escherichia coli

Escherichia coli that produce plasmid-mediated AmpC beta-lactamases are rare in the United States. The clinical features associated with infection with these organisms have not been well described. We identified 2 clinical isolates of E. coli that produced the plasmid-mediated AmpC enzyme beta-lactamase CMY-2. These organisms were recovered from urine specimens and were resistant to ceftazidime, ceftriaxone, and cefepime. One isolate was resistant to ertapenem but susceptible to imipenem and meropenem; the other was susceptible to imipenem, meropenem, and ertapenem. One of the 2 infected patients did not require specific therapy; the other required imipenem for cure. The presence of the CMY-2 beta-lactamase was confirmed by DNA sequencing. Hybridization studies confirmed that the bla(CMY-2) gene was on a plasmid in both isolates; in one of them, the probe also hybridized with chromosomal DNA. Infection with plasmid-mediated AmpC beta-lactamases in E. coli in the United States may be associated with treatment failure, and these strains may become a serious nosocomial threat.

Clonal Features of Community-Acquired Methicillin-Resistant Staphylococcus aureus in Children

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Nosocomial superinfections due to linezolid-resistant Enterococcus faecalis: evidence for a gene dosage effect on linezolid MICs

Resistance to linezolid among Enterococcus faecium and Enterococcus faecalis isolates has been reported in patients who receive a prolonged course of the drug. We report two cases of linezolid-resistant Enterococcus faecalis that occurred in patients who previously received linezolid for infections with vancomycin-resistant Enterococcus faecium. Both isolates had the G2576U mutation in the 23S rRNA previously reported in isolates of Enterococcus faecium. The number of gene copies mutated in the 23S rRNA correlated with the level of resistance.

Frequency, pathogenicity and microbiologic outcome of non-Candida albicans candiduria

A retrospective review of urine cultures obtained from patients at the University of Illinois Hospital revealed that the frequency of isolation of non-albicans Candida species increased significantly from 1990 to 1991 (p=0.0003), while the frequency of isolation ofCandida albicans species decreased significantly (p=0.0006). Patients with urine cultures positive for non-albicans Candida species orTorulopsis glabrata during 1991 were identified for review. Sixty-seven patients were eligible for evaluation. Non-albicans candiduria developed in an average of 12 days. Identical fungal species were isolated from the blood following a positive urine culture in only two patients. Twenty patients were treated; candiduria persisted in 9 (45 %), while resolution occurred in 11 (55 %). The remaining 47 patients were not treated. Non-albicans candiduria persisted in 30 (64 %) of these patients and resolved in 15 (32 %); in the remaining two patients (4 %) the microbiologic outcome was undetermined. The difference in microbiologic outcomes between treated and untreated patients was not significant using the Chi-square test (p=0.170). Non-albicans candiduria developed rapidly, frequently persisted whether treated or untreated, and rarely progressed to candidemia.

In vitro activities of metronidazole and its hydroxy metabolite against Bacteroides spp.

Metronidazole is metabolized to two major oxidative products: an acid metabolite and a hydroxy metabolite. While the activity of the acid metabolite is negligible, the activity of the hydroxy metabolite is approximately 65% of the activity of the parent drug. Pharmacokinetic studies of metronidazole and its hydroxy metabolite have shown that the MICs of both compounds remain above the MICs for most anaerobic organisms over an 8-h dosing interval. By a checkerboard assay, the combined activities of metronidazole and the hydroxy metabolite were examined against 4 quality control strains of Bacteroides species. Macrobroth tube dilutions were set up with Wilkins-Chalgren broth. Serial twofold dilutions of each agent were performed to achieve final concentrations ranging from 0.06 to 4.0 micrograms/ml. The MICs for Bacteroides fragilis and B. distasonis were 1.0 microgram/ml for both parent drug and metabolite. For B. thetaiotamicron and B. ovatus, the MICs of metronidazole and the hydroxy metabolite were 1.0 and 2.0 micrograms/ml, respectively. Synergy was determined by calculating the fractional inhibitory concentration (FIC) index. The interpretative criteria for the FIC index were as follows: synergy, FIC < or = 0.5; partial synergy, 0.51 to 0.75; indifference, FIC 0.76 to 4.0; and antagonism, FIC > 4.0. Partial synergy was observed for the four anaerobes tested, with FIC indices ranging from 0.63 to 0.75. On the basis of this data, in vitro susceptibilities to agents such as metronidazole may ultimately require reevaluation to account for active metabolites.

Detection of group B streptococcus: Comparison of an optical immunoassay with direct plating and broth-enhanced culture methods

The aim of this study was to compare the diagnostic accuracy of an optical immunoassay (STREP B OIA, Biostar) to direct plating and broth-enhanced culture for the detection of group B streptococcus (GBS) colonization of the lower genital tract in pregnant women. GBS cultures from the lower genital tract were obtained in a prospective fashion using a dual swab transport system from patients with risk factors for perinatal GBS infection. One swab was used to inoculate a trypticase soy agar plate with 5% sheep blood (TSA) and then placed in Lim broth. The other swab was used to perform the Strep B OIA. Growth of GBS by either direct plating or broth-enhanced culture was used as the gold standard for determining GBS colonization. Of the 524 women in the study, 90 women had positive cultures (either TSA or Lim broth). The sensitivity, specificity, positive predictive value, and negative predictive value of the Strep B OIA were 47% (42/90), 96% (416/434), 70% (42/60), 90% (416/464). The sensitivity, specificity, positive predictive value, and negative predictive value of the TSA were 61% (55/90), 100% (434/434), 100% (55/55), 93% (434/469). The sensitivity, specificity, positive predictive value, and negative predictive value of Lim broth were 97% (87/90), 100% (434/434), 100% (87/87), and 97% (434/437). The sensitivity of the Strep B OIA to detect light GBS colonization and heavy GBS colonization, as determined by the TSA, was 53% (19/36) and 90% (17/19), respectively. The Strep B OIA and direct agar plate culture appear to be of limited clinical value due to their poor sensitivities. This study also demonstrates the need to use a selective medium such as Lim broth when assessing for GBS colonization of the lower genital tract.

In vitro activity of clarithromycin alone and in combination with ciprofloxacin or levofloxacin against Legionella spp.: Enhanced effect by the addition of the metabolite 14-hydroxy clarithromycin☆

Clarithromycin is metabolized to an active metabolite, 14-hydroxy clarithromycin. These compounds have demonstrated excellent in vitro activity against Legionella species, with both agents having significantly lower MICs than erythromycin. Using a checkerboard assay, the activity of clarithromycin and its hydroxy metabolite, alone and in combination, was examined against 41 Legionella organisms. The activity of clarithromycin and 14-hydroxy clarithromycin, in a 2:1 ratio, plus ciprofloxacin or levofloxacin was also determined. Activity of the antibiotic combinations was determined by calculating the fractional inhibitory concentration index. An agar dilution method using buffered charcoal yeast extract media was used for susceptibility and synergy testing. An inoculum of 10(4) CFU/spot was used, with all plates incubated at 35 degrees C for 48 h. The MIC90 for clarithromycin or 14-hydroxy clarithromycin alone was 0.5, versus 0.25 microgram/mL for the combination. Additive effects were observed with clarithromycin and its hydroxy metabolite for 61% of the Legionella species, with fractional inhibitory concentration indices ranging from 0.63 to 1.25. The 14-hydroxy metabolite significantly increased the activity of both fluoroquinolone/clarithromycin combinations. Based on these data, in vitro susceptibility testing of agents such as clarithromycin should be reevaluated to account for the activity of active metabolites.