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G L Archer

Publications and source records attributed to G L Archer.

At least 55 records · Page 3Linked to original sources
PubMed1988

Molecular epidemiology of multiresistant Staphylococcus epidermidis.

Molecular epidemiology has provided several clues about the antimicrobial resistance genes of nosocomial, multiresistant coagulase-negative staphylococci. First, it has shown that a huge reservoir of resistance genes is maintained in these organisms on the bodies of both patients and the hospital personnel who care for them. In turn, extensive use of antimicrobial agents within specific sectors of the hospital probably provides selection pressure for the evolution and amplification of these genes. Secondly, indirect evidence suggests that Staphylococcus epidermidis may itself serve as a reservoir for antimicrobial resistance genes that are transferred to S. aureus.

Conjugation, Genetic↗
PubMed1987

Native valve endocarditis due to coagulase-negative staphylococci. Clinical and microbiologic features.

Twenty-one patients with native valve endocarditis caused by coagulase-negative staphylococci were studied; 14 had pre-existing valvular or congenital heart disease. Although commonly subacute in presentation, complications of endocarditis were frequent: arterial emboli in five patients, new electrocardiographic conduction system abnormalities in nine, congestive heart failure in eight, annular or myocardial abscesses in five, and disruption of valve leaflets in three. Cures were achieved in 10 of 12 patients treated medically and seven of nine treated surgically. In microbiologic studies of 16 coagulase-negative staphylococci from patients with endocarditis, only eight were identified as Staphylococcus epidermidis. All isolates were susceptible to vancomycin. Antibiotic resistance (methicillin, four isolates; gentamicin, two isolates; rifampin, one isolate) was usually associated with nosocomial acquisition of endocarditis. Rather than representing contamination, coagulase-negative staphylococci in blood cultures may indicate life-threatening endocarditis. However, with careful attention to the selection of antibiotics for therapy and to the occurrence of heart failure due to intracardiac complications, treatment of this form of endocarditis is frequently successful. Organisms must always be tested for cryptic resistance to beta-lactam antibiotics. Valve replacement may be required frequently.

Anti-Bacterial Agents↗
PubMed1987

In-vitro activity of LY146032 against Staphylococcus aureus and S. epidermidis.

The antibacterial activity of LY146032, a new cyclic polypeptide, was compared with that of vancomycin against 163 isolates of methicillin-susceptible and methicillin-resistant Staphylococcus aureus and S. epidermidis. The MICs of LY146032 and vancomycin for 90% of the isolates were 1.0 mg/l and 2.0-4.0 mg/l, respectively. Interpretative guidelines for 15 micrograms and 30 micrograms LY146032 discs could not be established because all isolates tested were susceptible to LY146032, on the basis of achievable serum levels. With one exception, MBC to MIC ratios of LY146032 and vancomycin were less than or equal to 2. Inoculum size had minimal effect on ratios. In time-kill studies, both drugs were 99.9% bactericidal at 6 h for four isolates at concentrations four times the MBC or less. No change in LY146032 activity was observed between isogenic pairs that were resistant to other antibiotics. Thus, LY146032 was very active in vitro against all staphylococcal isolates.

Anti-Bacterial Agents↗
PubMed1987

Molecular epidemiology of trimethoprim resistance among coagulase-negative staphylococci.

A 42% (70 of 167 isolates) incidence of resistance to 20 micrograms of trimethoprim per ml was found among clinical isolates of coagulase-negative staphylococci from two hospitals. A specific trimethoprim resistance gene probe from a conjugative Staphylococcus aereus plasmid was used to investigate the location of the trimethoprim resistance gene among 29 isolates. In 14 trimethoprim-resistant isolates, the probe hybridized with only chromosomal DNA, in 9 it hybridized with only plasmid DNA, and in 1 isolate both plasmid and chromosomal sequences showed hybridization. In five isolates there was no hybridization of the probe with either chromosomal or plasmid DNA. Four of these five nonhybridizing isolates were Staphylococcus haemolyticus. In contrast, all 22 Staphylococcus epidermidis isolates tested hybridized with the probe. The presence of the trimethoprim resistance gene in a chromosomal location was correlated with a lower MIC (median, 80 micrograms/ml) than when it was plasmid encoded (median, 1,250 micrograms/ml). Restriction endonuclease mapping as well as DNA hybridization of cloned plasmid and chromosomal DNA showed that there were 2.7 kilobases of common DNA in the two loci. This included the 500 base pairs of DNA mediating trimethoprim resistance and a total of 2.2 kilobases of 3'- and 5'-flanking sequences. The presence of the same gene and flanking sequences in chromosomal and plasmid locations suggests that the trimethoprim resistance determinant is translocated among different genetic loci.

Chromosome Mapping↗
PubMed1987

Characterization of a staphylococcal trimethoprim resistance gene and its product.

Resistance to trimethoprim (Tp) is mediated by a plasmid-encoded gene in staphylococci. The gene is responsible for high-level resistance (MIC, greater than 1,000 micrograms/ml) in both its native host and when cloned on high-copy-number vectors in Escherichia coli. Analysis of subclones of the staphylococcal Tp gene on E. coli expression vectors and estimation of the size of full and truncated proteins produced in E. coli minicells generated an approximate size limit of 505 base pairs for the gene and 18,500 daltons for the gene product. Crude extracts of E. coli containing the cloned gene had dihydrofolate reductase (DHFR) specific activity that was more than 100 times greater than that of control cells and more than 1,000 times more resistant to trimethoprim inhibition. The amount of trimethoprim required for a 50% reduction in the specific activity of staphylococcal DHFR differed from those of cells containing DHFR types I, II, or III, enzymes mediating Tp in members of the family Enterobacteriaceae. In addition, the size of the monomeric staphylococcal DHFR protein was larger than that of any of the gram-negative DHFRs both compared with published sequence data and as observed by direct comparison on polyacrylamide gels. Finally, there was no homology between a DNA fragment containing the cloned staphylococcal gene and DNA encoding any of the gram-negative DHFRs. Thus, the staphylococcal Tp gene codes for a single protein with DHFR activity that appears to be unrelated to DHFR genes that mediate Tp in members of the Enterobacteriaceae.

Cloning, Molecular↗
PubMed1986

Plasmid-encoded trimethoprim resistance in staphylococci.

High-level (greater than 1,000 micrograms/ml) resistance to the antimicrobial agent trimethoprim was found in 17 of 101 (17%) coagulase-negative staphylococci and 5 of 51 (10%) Staphylococcus aureus from a number of different hospitals in the United States. Resistance was plasmid encoded and could be transferred by conjugation in 4 of the 17 (24%) Tpr coagulase-negative staphylococci and 3 of the 5 (60%) Tpr S. aureus. A 1.2-kilobase segment of plasmid DNA from one of the plasmids (pG01) was cloned on a high-copy-number vector in Escherichia coli and expressed high-level Tpr (MIC, 1,025 micrograms/ml) in the gram-negative host. In situ filter hybridization demonstrated homology between the cloned Tpr gene probe and plasmid DNA from each conjugative Tpr plasmid, a single nonconjugative plasmid from a United States Staphylococcus epidermidis isolate, a nonconjugative plasmid from an Australian methicillin-resistant S. aureus isolate, and chromosomal DNA from three Tpr S. epidermidis isolates that did not contain any plasmid DNA that was homologous with the probe. No homology was seen between the probe and staphylococcal plasmids not mediating Tpr, plasmid DNA from 12 Tpr S. epidermidis isolates not transferring Tpr by conjugation, or plasmid-encoded Tpr genes derived from gram-negative bacteria. Plasmid-encoded Tpr appears to be a relatively new gene in staphylococci and, because it can be transferred by conjugation, could become more prevalent in nonsocomial isolates.

Cloning, Molecular↗
PubMed1986

Imipenem therapy of experimental Staphylococcus epidermidis endocarditis.

Imipenem was evaluated for its activity against Staphylococcus epidermidis in vitro and in a rabbit model of endocarditis. The MBC for imipenem of 55 methicillin-resistant S. epidermidis isolates from patients with prosthetic valve endocarditis increased by eightfold or greater with increasing inoculum size; there was no inoculum-associated increase in the imipenem MBC for 20 methicillin-susceptible S. epidermidis isolates. Endocarditis was produced in rabbits with either a methicillin-susceptible or a methicillin-resistant S. epidermidis isolate to investigate the correlation in vivo of the in vitro inoculum effect for imipenem. Six days of imipenem treatment eradicated methicillin-susceptible S. epidermidis from vegetations of infected rabbits significantly better than no therapy but was less effective against methicillin-resistant S. epidermidis in this regard. Among methicillin-resistant S. epidermidis-infected rabbits, 6 days of imipenem therapy (i) was not significantly better than that of the control and was significantly worse than that of vancomycin in eradicating bacteria from infected vegetations and (ii) increased the frequency of imipenem-resistant subpopulations in infected vegetations. Resistant subpopulations were not seen in vegetations from untreated or imipenem-treated, methicillin-susceptible S. epidermidis-infected rabbits. Imipenem may not be effective therapy for serious human methicillin-resistant S. epidermidis infections.

Animals↗
PubMed1986

Evaluation of laboratory tests for detection of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis.

Few studies evaluating susceptibility testing of methicillin-resistant staphylococci have included isolates of Staphylococcus epidermidis, a known pathogen in many types of serious infections. We tested 175 S. epidermidis and 95 Staphylococcus aureus isolates to determine the most sensitive procedures for detecting methicillin-resistant staphylococci. Reference procedures included agar dilution with methicillin and 4% NaCl in the agar and broth microdilution with methicillin and 2% NaCl in cation-supplemented Mueller-Hinton broth. After 24 h of incubation, the results from both methods correlated well and were within 1 log2 dilution for all isolates tested. Only one-half of all resistant isolates (92 of 183) were detected at 18 h by using the standard disk diffusion technique with 5-micrograms methicillin disks, and even fewer were detected with 10-micrograms methicillin disks and newly recommended zone-size criteria. However, the standard disk diffusion method with 4% NaCl in the agar increased the sensitivity and specificity for identification of the proper phenotype to greater than 92%. The spread plate and new spot techniques, both using agar with 4% NaCl, were also sensitive methods. Of 47 S. epidermidis isolates tested against oxacillin, 6 (13%) were oxacillin susceptible but methicillin resistant. Two automated systems, the Automicrobic system (Vitek Systems) and MicroScan (American MicroScan), as well as two broth screening systems available from Remel and Austin Biological Laboratories, failed to detect several resistant isolates, depending on the species.

Culture Media↗
PubMed1985

Molecular epidemiology of transmissible gentamicin resistance among coagulase-negative staphylococci in a cardiac surgery unit.

The prevalence of colonization of patients in a cardiac surgery unit with gentamicin-resistant, coagulase-negative staphylococci increased from 20% to 68% over a period of four years. Gentamicin resistance was found to be plasmid associated and transmissible from wild-type coagulase-negative staphylococcal donors to a Staphylococcus aureus recipient by filter mating (conjugative). These plasmids were present in isolates from 50 (74%) of 69 individuals examined. This figure included isolates from colonized patients, colonized staff, and patients with prosthetic valve endocarditis. A common restriction-endonuclease digestion pattern (pG02; 50 kilobases) was seen in only 19 (38%) of the 50 conjugative plasmids. However, filter hybridization, restriction-endonuclease mapping, and transposon insertional mutagenesis showed that representatives of the other 10 restriction-endonuclease digestion patterns were physically related to pG02 over greater than 80% of their genome, with differences largely due to deletions or insertions of DNA in three areas, and that their gentamicin-resistance genes were identical. Molecular analysis may be required to ascertain the physical similarity among phenotypically and epidemiologically related plasmids.

Cardiac Surgical Procedures↗
PubMed1984

Plasmid-pattern analysis for the differentiation of infecting from noninfecting Staphylococcus epidermidis.

Isolation of Staphylococcus epidermidis from cultures of blood was differentiated from culture contamination by the detection of identical isolates in two or more consecutive cultures from an infected patient. We used plasmid-pattern analysis as a tool for establishing the identity of individual isolates. In a control study of 15 patients with two or more cultures of blood contaminated with S. epidermidis, analysis revealed that none of the isolates had identical plasmid patterns. This reflected the variety of plasmid patterns among colonizing coagulase-negative staphylococci cultured from skin sites of uninfected patients. In contrast, plasmid-pattern identity was seen among sequential or paired S. epidermidis isolates from a given patient in 32 of 36 patients with documented S. epidermidis infection. The plasmid pattern of each set of isolates from patients was unique. Infections included prosthetic-valve endocarditis in 26 patients, cerebrospinal fluid-shunt or ventriculostomy infections in six patients, intravenous-catheter sepsis in two patients, urinary tract infection in one patient, and osteomyelitis in one patient. Plasmid-pattern analysis may therefore be useful in the diagnosis of S. epidermidis infections.

Anti-Bacterial Agents↗
PubMed1983

Alteration of staphylococcal flora in cardiac surgery patients receiving antibiotic prophylaxis.

The changes in staphylococcal flora induced by antibiotic prophylaxis with rifampin and nafcillin in combination among patients undergoing cardiac valve surgery were compared to those in patients undergoing coronary artery bypass surgery concurrently, who received only cefazolin. Rifampin-nafcillin prophylaxis eradicated carriage of Staphylococcus aureus at a significantly higher rate than did cefazolin (eradicated carriage of 89% vs. 48%, respectively; P less than 0.01); however, by the seventh postoperative day, 75% of the patients receiving rifampin and nafcillin had rifampin-resistant, coagulase-negative staphylococcal perianal floras, compared to 19% of those who received cefazolin (P less than 0.001). Patients receiving rifampin-nafcillin were colonized as frequently (66%) with coagulase-negative staphylococci resistant to gentamicin and methicillin as were those receiving cefazolin (68%). Patients in the coronary intensive care unit who received no antibiotics were infrequently colonized with either rifampin-resistant (none) or gentamicin- and methicillin-resistant (11%) staphylococci. Antibiotic prophylaxis may, therefore, be an important factor in perpetuating the hospital reservoir for antibiotic-resistant, coagulase-negative staphylococci.

Anti-Bacterial Agents↗
PubMed1983

Self-transmissible plasmids in staphylococci that encode resistance to aminoglycosides.

High-level resistance to gentamicin, tobramycin, and kanamycin was transferred between staphylococci of the same and different species by filter mating. Resistance and transfer proficiency were mediated by plasmids ranging from 38 to 54 kilobases in size. All of the plasmids encoded intermediate resistance to amikacin and netilmicin and resistance to ethidium bromide; some encoded beta-lactamase production. None of these plasmids carried resistance to other antibiotics or heavy metals. Transfer of antibiotic resistance occurred by a mechanism similar to that of conjugation, because it was DNase resistant, required cell-to-cell contact, and did not appear to involve phage. The participation of phage in transfer appeared to be unlikely because mijtomicin C-induced lysates of donor isolates did not mediate transfer, filter mating transfer proceeded at high frequency between nonlysogenic donor and recipient cells, and transfer of the aminoglycoside resistance plasmid mobilized the transfer of as many as five additional plasmids. All 17 gentamicin-resistant Staphylococcus aureus and all 6 Staphylococcus epidermidis isolates obtained from an outbreak of staphylococcal infections in a newborn nursery contained conjugative plasmids, as did all 6 gentamicin-resistant S. aureus isolates from bacteremic adults. However, only 3 of 10 gentamicin-resistant S. epidermidis isolates from colonized cardiac surgery patients and 1 of 2 S. epidermidis isolates from patients with prosthetic valve endocarditis transferred gentamicin resistance by filter mating. The recent increase in nosocomial infections caused by gentamicin-resistant staphylococci may be partially explained by the evolution of self-transmissible plasmids in these isolates.

Aminoglycosides↗
PubMed1983

Comparison of epidemiological markers used in the investigation of an outbreak of methicillin-resistant Staphylococcus aureus infections.

An outbreak of nosocomial infections was caused by a single strain of methicillin-resistant (MR) Staphylococcus aureus. This strain was followed as it was transmitted from the index case to 17 patients, 3 hospital personnel, and 12 items in the hospital environment. The MR S. aureus strain was traced by using four specific epidemiological markers: antibiogram, phage type, production of aminoglycoside-inactivating enzymes, and plasmid pattern. These markers were assessed for their reliability in differentiating the epidemic S. aureus strain from resident nonepidemic strains and for the ease and rapidity with which they determined differences. The epidemic strain was resistant to beta-lactam antibiotics, gentamicin, erythromycin, clindamycin, and rifampin. Resistance to rifampin was the only unique marker in the antibiogram which distinguished the epidemic strain from the indigenous strains, and it was the easiest marker to use for screening isolates from culture surveys. Phage typing was poorly reproducible and did not yield results rapidly enough to be useful for ongoing epidemiology. The epidemic strain produced a unique aminoglycoside-inactivating enzyme (3'-phosphotransferase) which distinguished it from indigenous gentamicin-resistant staphylococci, but this marker was not easily identified, nor was identification helpful during the course of the investigation. Plasmid pattern analysis was rapidly performed (in less than 24 h), allowed many isolates to be examined at a time, was stable and reproducible, and yielded a unique fingerprint which distinguished the epidemic strain from all indigenous isolates. Plasmid pattern analysis is a promising epidemiological tool for MR S. aureus outbreaks in which epidemic strains lack unique antibiotic resistance markers.

Bacteriophage Typing↗
PubMed1983

Staphylococcus epidermidis causing prosthetic valve endocarditis: microbiologic and clinical observations as guides to therapy.

Seventy-five episodes of prosthetic valve endocarditis from Staphylococcus epidermidis were studied retrospectively. Methicillin-resistant isolates caused 53 (87%) of 61 infections occurring within 1 year of surgery but only two of the nine after 1 year (p less than 0.001). Resistance to methicillin was heterogeneic and extended to the cephalosporins. Of 55 isolates, 43 (78%) were susceptible to gentamicin and all to vancomycin and rifampin. In 55 patients, prosthetic valve endocarditis was complicated by tissue invasion or valve dysfunction. Among these 55 patients, 30 of the 32 who were cured needed surgery. Prosthetic valve endocarditis from methicillin-resistant S. epidermidis was cured in 21 of 26 patients treated with vancomycin and 10 of 20 treated with beta-lactam antibiotic therapy (p = 0.055). Cure rates of patients treated with vancomycin but not beta-lactam antibiotics were increased by the addition of rifampin or gentamicin to therapy. Prosthetic valve endocarditis from methicillin-resistant S. epidermidis should be treated with vancomycin plus rifampin, or an aminoglycoside. Surgical intervention is important in treating complications of prosthetic valve endocarditis.

Adolescent↗
PubMed1982

Rifampin blood and tissue levels in patients undergoing cardiac valve surgery.

Single 600-mg capsules of rifampin were given orally to 26 patients as prophylaxis during cardiac valve replacement. Antibiotic concentrations were measured in blood (serum or plasma) and tissue (excised cardiac valve). The serum or plasma levels of rifampin in 18 patients who ingested this drug 2 h before they received preoperative opiates and anticholinergics intramuscularly were not significantly different from the levels in four normal volunteers who received the drug. These levels were 15.9 +/- 6.5 micrograms/ml (mean +/- standard deviation) 2 h after drug administration, 7.1 +/- 4.3 micrograms/ml 8 h after drug administration and 2 h after a mean of 1.4 h on cardiopulmonary bypass, and 1.6 +/- 1.6 micrograms/ml 24 h after drug ingestion. The valve tissue level was 3.8 +/- 2.7 micrograms/g (mean +/- standard deviation; n = 10). This value was 65% of the simultaneous serum and plasma levels and 31% of the peak serum and plasma levels. Eight patients who were given rifampin at the same time that they received other preoperative medications had significantly lower blood levels than the 18 patients who received rifampin 2 h earlier (P less than 0.001). No rifampin was detected in valves from seven of these patients. Decreased rifampin absorption due to simultaneous administration with opiates and anticholinergics was the probable reason for the low plasma and serum levels observed. These data suggest that, if properly dosed, rifampin administered orally gives high blood and valve tissue levels, which are affected minimally by cardiopulmonary bypass in patients undergoing cardiac valve surgery.

Female↗
PubMed1982

Plasmid pattern analysis of Staphylococcal epidermidis isolates from patients with prosthetic valve endocarditis.

The electrophoretic pattern formed by individual bacterial plasmid DNA molecules of differing molecular size was evaluated as an epidemiological marker among isolates of Staphylococcus epidermidis from patients with prosthetic valve endocarditis (PVE). Purified covalently closed circular plasmid DNA was obtained from selected isolates, and 79% of the plasmids were found to be less than 10 megadaltons in size; only these small plasmids were sought in subsequent screening gels. Crude cell lysates obtained by a rapid lysis technique and screened by agarose gel electrophoresis revealed the presence of one or more small plasmids in 54 of 58 (93%) PVE isolates; 79% contained two or more. Among 45 plasmid-containing isolates from cases of sporadic PVE at three institutions there were no identical plasmid patterns, although several isolates differed by a single plasmid. In contrast, among nine isolates from a cluster of cases of PVE in Canada, two groups of three isolates each had identical plasmid patterns. Additional clinical data suggested that these isolates were epidemiologically related. Phage typing distinguished one of the groups with plasmid pattern identity, but not the other, from the three isolates with dissimilar patterns. Plasmid pattern analysis shows promise as an epidemiological marker for clinically important isolates of S. epidermidis.

DNA, Circular↗