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M J Zervos

Publications and source records attributed to M J Zervos.

At least 37 records · Page 2Linked to original sources
PubMed1998

New antimicrobial agents for Gram-positive infections.

Increasing antimicrobial resistance in Gram-positive bacteria has presented a formidable treatment problem. The enterococci, although traditionally non-virulent pathogens, have been shown, when associated with vancomycin resistance, to have an attributable mortality of approximately 40%. The frightening specter of widespread vancomycin resistance in the more virulent Staphylococcus aureus would have a significantly greater impact. Since the late 1980s, advances have been made in the development of pharmacological weapons against multiply resistant Gram-positive bacterial infections. At least seven new antimicrobial classes that have activity against resistant Gram-positive organisms are in various stages of development. Most are semisynthetic derivatives of known antibiotics; however, importantly, a unique class of antimicrobial agent has also emerged.

Journal Article↗
PubMed1998

Treatment of vancomycin-resistant Enterococcus faecium with RP 59500 (quinupristin-dalfopristin) administered by intermittent or continuous infusion, alone or in combination with doxycycline, in an in vitro pharmacodynamic infection model with simulated endocardial vegetations.

Quinupristin-dalfopristin is a streptogramin antibiotic combination with activity against vancomycin-resistant Enterococcus faecium (VREF), but emergence of resistance has been recently reported. We studied the activity of quinupristin-dalfopristin against two clinical strains of VREF (12311 and 12366) in an in vitro pharmacodynamic model with simulated endocardial vegetations (SEVs) to determine the potential for resistance selection and possible strategies for prevention. Baseline MICs/minimal bactericidal concentrations (microg/ml) for quinupristin-dalfopristin, quinupristin, dalfopristin, and doxycycline were 0.25/2, 64/>512, 4/512, and 0.125/8 for VREF 12311 and 0.25/32, 128/>512, 2/128, and 0.25/16 for VREF 12366, respectively. Quinupristin-dalfopristin regimens had significantly less activity against VREF 12366 than VREF 12311. An 8-microg/ml simulated continuous infusion was the only bactericidal regimen with time to 99.9% killing = 90 hours. The combination of quinupristin-dalfopristin every 8 h with doxycycline resulted in more killing compared to either drug alone. Quinupristin-dalfopristin-resistant mutants (MICs, 4 microg/ml; resistance proportion, approximately 4 x 10(-4)) emerged during the quinupristin-dalfopristin monotherapies for both VREF strains. Resistance was unstable in VREF 12311 and stable in VREF 12366. The 8-microg/ml continuous infusion or addition of doxycycline to quinupristin-dalfopristin prevented the emergence of resistance for both strains over the 96-h test period. These findings replicated the development of resistance reported in humans and emphasized bacterial factors (drug susceptibility, high inoculum, organism growth phase) and infectious conditions (penetration barriers) which could increase chances for clinical resistance. The combination of quinupristin-dalfopristin with doxycycline and the administration of quinupristin-dalfopristin as a high-dose continuous infusion warrant further study to determine their potential clinical utility.

Anti-Bacterial Agents↗
PubMed1998

Antimicrobial resistance in enterococci isolated from Turkey flocks fed virginiamycin.

From 125 separate cloacal cultures from three turkey flocks fed virginiamycin, 104 Enterococcus faecium and 186 Enterococcus faecalis isolates were obtained. As the turkeys aged, there was a higher percentage of quinupristin-dalfopristin-resistant E. faecium isolates, with isolates from the oldest flock being 100% resistant. There were no vancomycin-resistant enterococci. Results of pulsed-field gel electrophoresis (PFGE) indicated there were 11 PFGE types of E. faecalis and 7 PFGE types of E. faecium that were in more than one group of flock cultures.

Animals↗
PubMed1998

A new high-level gentamicin resistance gene, aph(2'')-Id, in Enterococcus spp.

Enterococcus casseliflavus UC73 is a clinical blood isolate with high-level resistance to gentamicin. DNA preparations from UC73 failed to hybridize with intragenic probes for aac(6')-Ie-aph(2'')-Ia and aph(2'')-Ic. A 4-kb fragment from UC73 was cloned and found to confer resistance to gentamicin in Escherichia coli DH5alpha transformants. Nucleotide sequence analysis revealed the presence of a 906-bp open reading frame whose deduced amino acid sequence had a region with homology to the aminoglycoside-modifying enzyme APH(2'')-Ic and to the C-terminal domain of the bifunctional enzyme AAC(6')-APH(2''). The gene is designated aph(2'')-Id, and its observed phosphotransferase activity is designated APH(2'')-Id. A PCR-generated intragenic probe hybridized to the genomic DNA from 17 of 118 enterococcal clinical isolates (108 with high-level gentamicin resistance) from five hospitals. All 17 were vancomycin-resistant Enterococcus faecium isolates, and pulsed-field typing revealed three distinct clones. The combination of ampicillin plus either amikacin or neomycin exhibited synergistic killing against E. casseliflavus UC73. Screening and interpretation of high-level aminoglycoside resistance in enterococci may need to be modified to include detection of APH(2'')-Id.

Anti-Bacterial Agents↗
PubMed1998

Molecular analysis of glycopeptide-resistant Enterococcus faecium isolates collected from Michigan hospitals over a 6-year period.

The purpose of this study was to evaluate the molecular relatedness of clinical isolates of glycopeptide-resistant Enterococcus faecium isolates collected from hospitals in Michigan. A total of 379 isolates used in this study were all vancomycin-resistant E. faecium isolates collected from 28 hospitals and three extended-care facilities over a 6-year period from 1991 to 1996. For the 379 isolates, there were 73 pulsed-field gel electrophoresis (PFGE) strain types. Within strain types, there were as many as six restriction fragment differences. Most isolates (70%) belonged to six strain types, which were designated M1 (36%), M2 (3%), M3 (18%), M4 (6%), M10 (4%), and M11 (3%). PFGE strain M1 was cultured from 135 patients in 13 hospitals during the period 1993 to 1996. Strain type M2 was cultured from 11 patients in two hospitals during the period 1991 to 1992 and was not observed after 1992. Strain type M3 was cultured from 70 patients in 10 hospitals during the period of 1994 to 1996. Both M4 and M10 were cultured from 23 patients in three hospitals and from 15 patients in two hospitals, respectively, during 1995 to 1996. M11 was cultured from 13 patients in four hospitals during 1996. A total of 23 of 28 hospitals had evidence of clonal dissemination of some isolates. Plasmid content and hybridization analysis done on 103 isolates from one hospital and two affiliated extended-care facilities indicated that the strains contained from one to eight plasmids. Mating experiments indicated transfer of vancomycin resistance from 94 of these isolates into plasmid-free E. faecium GE-1 at transfer frequencies of <10(-9) to 10(-4). Gentamicin resistance and erythromycin resistance were cotransferred at various frequencies. A probe for the vanA gene hybridized to the plasmids of 23 isolates and to the chromosomes of 72 isolates. A probe for the vanB gene hybridized to the chromosomes of 8 isolates. The results of this study suggest inter- and intrahospital dissemination of vancomycin-resistant E. faecium strains over a 6-year period in southeastern Michigan. The majority of isolates studied belonged to the same few PFGE strains, indicating that clonal dissemination was responsible for most of the spread of resistance that occurred.

Anti-Bacterial Agents↗
PubMed1998

Nosocomial Candida glabrata colonization: an epidemiologic study.

Candida glabrata has emerged as an important nosocomial pathogen, yet little is known about its epidemiology. We prospectively followed 98 patients admitted to a medical intensive care unit and the bone marrow transplant unit of a university hospital. Samples from environmental surfaces and the hands of hospital personnel were also cultured. Patients with newly acquired C. glabrata strains were compared to controls who were culture negative for C. glabrata. C. glabrata was recovered from multiple sites from 24 patients and three environmental surfaces. Sixteen patients (17%) acquired C. glabrata after admission to the study units. Significant risk factors for the nosocomial acquisition of C. glabrata were prolonged duration of hospitalization in the unit and prior antimicrobial use. Strain delineation by restriction enzyme analysis revealed 28 different strains of C. glabrata; three strain types were common to nine patients. The environmental isolates were of the same strain type and common to five patients (four patients with newly acquired strains). These results suggest the possibility of exogenous nosocomial acquisition of C. glabrata, including the possible acquisition from the hospital environment. Transmission may be by indirect contact since identical strains of C. glabrata were recovered from patients who were geographically and temporally associated.

Adult↗
PubMed1998

Epidemiologic evaluation of antimicrobial resistance in community-acquired enterococci.

Fecal samples from 200 consecutive patients admitted to a community hospital yielded 107 enterococci. High-level gentamicin resistance occurred in 10 (14%) of the Enterococcus faecalis isolates. Ampicillin resistance occurred in two (3%) of the E. faecalis isolates and six (23%) of the Enterococcus faecium isolates. There were no vancomycin-resistant enterococci. Risk factors for enterococci with high-level aminoglycoside (gentamicin) or ampicillin resistance included prior hospitalization and previous antibiotic use.

Adult↗
PubMed1997

A novel gentamicin resistance gene in Enterococcus.

Enterococcus gallinarum SF9117 is a veterinary isolate for which the MIC of gentamicin is 256 micrograms/ml. Time-kill studies with a combination of ampicillin plus gentamicin failed to show synergism against SF9117. A probe representing aac(6')-aph(2") did not hybridize to DNA from SF9117. A 3.2-kb fragment from plasmid pYN134 of SF9117 was cloned and conferred resistance to gentamicin in Escherichia coli DH5 alpha. Nucleotide sequence analysis revealed the presence of a 918-bp open reading frame whose deduced amino acid sequence had a region with homology to the C-terminal domain of the bifunctional enzyme AAC(6')-APH(2"). The gene is designated aph(2")-Ic, and its observed phosphotransferase activity is provisionally designated APH(2")-Ic. An intragenic probe hybridized to the genomic DNA from an Enterococcus faecium isolate from the peritoneal fluid of one patient and to the plasmid DNA of an Enterococcus faecalis isolate from the blood of another patient. An enterococcal isolate containing this novel resistance gene might not be readily detected in clinical laboratories that use gentamicin at 500 or 2,000 micrograms/ml for screening for high-level resistance.

Amino Acid Sequence↗
PubMed1997

The effect of Tn916 insertions on contour-clamped homogeneous electrophoresis patterns of Enterococcus faecalis.

Contour-clamped homogeneous gel electrophoresis has increasingly been used and has generally been considered the method of choice for the delineation of enterococcial strains. It has been suggested that the contour-clamped homogeneous electric field (CHEF) electrophoresis digestion patterns of genomic DNA indicate the relatedness of strains when SmaI patterns differ by six or fewer bands. To evaluate the potential reasons for the diversity of bands among clonally related isolates, we studied plasmid-free Enterococcus faecalis FA2-2 and derivatives with transposon Tn916 (encoding for tetracycline resistance) insertions on the chromosome. We obtained derivatives with seven different Tn916 insertion sites and up to two copies of Tn916 on the chromosome, resulting in differences of one to seven bands by CHEF electrophoresis; eight different patterns were observed. With Tn916 insertions, there was either (i) loss of a band(s) with the generation of a new band(s), (ii) the generation of a new band(s) only, or (iii) the loss of a band(s) with no new visible band(s). These results indicate that strains can have up to seven different SmaI bands by CHEF electrophoresis and still be closely related.

Bacterial Typing Techniques↗
PubMed1996

Comparative in vitro activity of quinupristin/dalfopristin against multidrug resistant Enterococcus faecium.

The in vitro susceptibilities of 82 strains of vancomycin resistant Enterococcus faecium (VREF), (49 vanA and 33 vanB) from over 13 hospitals in Europe and United States were studied. The MIC for several antibiotics showed high levels of resistance to vancomycin, ampicillin, gentamicin, and imipenem. All VREF strains were highly susceptible to quinupristin/dalfopristin with a MIC 90% of 0.5 microgram/ml for both vanA and vanB phenotypes. Time-kill and synergy studies of VREF for quinupristin/dalfopristin alone and quinupristin/dalfopristin in combination with several antibiotics (ampicillin, gentamicin, ciprofloxacin, rifampin and novobiocin) did not show bactericidal activity. In induction experiments using SF6550, (VREF, a vanA strain), quinupristin/dalforpristin showed a delay in the expression of vancomycin resistance by 2.5 hours. The results of this study show quinupristin/dalfopristin to have excellent in vitro activity versus multiple resistant E. faecium.

Anti-Bacterial Agents↗
PubMed1996

Control of endemic glycopeptide-resistant enterococci.

OBJECTIVE: To evaluate the epidemiology of, and control measures for, vancomycin-resistant Enterococcus (VRE) in a renal unit. DESIGN: A 3-month, prospective, prevalence culture survey of patients on a 24-bed renal unit. SETTING: A 975-bed community teaching hospital. PATIENTS: Patients admitted to the renal unit over a 3-month period. Patients identified with VRE were each matched with four patients without VRE isolated over the study period. INTERVENTIONS/CONTROL MEASURES: Resistant-organism barrier precautions. To eradicate carriage of VRE, two patients with VRE stool colonization were treated with 5 days of oral doxycycline (100 mg twice per day) and rifampin (300 mg/day). RESULTS: Seven patients with VRE (8 isolates) were identified. Five isolates were Enterococcus faecium (vancomycin MIC = 16 to 256 micrograms/mL), two were Enterococcus faecalis (MICs = 16 and 124 micrograms/mL), and one was Enterococcus gallinarum (MIC = 8.0 micrograms/mL). Eradication of carriage with VRE was accomplished in two patients treated with doxycycline and rifampin. In the final 30 days of the culture survey and at 9 months, there were no further patients with VRE identified. CONCLUSIONS: Resistant-organism precautions and elimination of patient carriage may be useful measures for controlling the spread of low-prevalence endemic vancomycin-resistant Enterococcus.

Adult↗
PubMed1996

DNA analysis in the study of fungal infections in the immunocompromised host.

Fungal infections, most of which are caused by the Candida species, are an increasing problem in the immunocompromised host. The clinical manifestations of Candida infections include disseminated candidiasis, oral and esophageal infections, focal hepatic infections, peritoneal urinary tract infections, and wound infections. DNA methods, which include pulse field electrophoresis and restriction enzyme analysis of genomic DNA, have been used to increase understanding of the epidemiology of these infections. These techniques have shown that most Candida infections are endogenous or acquired from one's own flora. Recent outbreaks have provided evidence for exogenous acquisition of some isolates. Better methods for differentiation of colonization versus infection and identifying infection in the absence of positive cultures are under investigation.

Adult↗