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Biomedical subjects

G L Archer

Publications and source records attributed to G L Archer.

69 records · Page 4Linked to original sources

Antibiotic prophylaxis of experimental endocarditis due to methicillin-resistant Staphylococcus epidermidis.

Antibiotic prophylaxis for the prevention of endocarditis due to methicillin-resistant Staphylococcus epidermidis (MRSE) was evaluated in a modified rabbit endocarditis model and compared with results obtained with methicillin-sensitive S. epidermidis (MSSE). One dose of nafcillin, cefamandole, cephalothin, or vancomycin neither prevented endocarditis nor sterilized the blood of rabbits challenged with each of two MRSE or two MSSE isolates. One dose of gentamicin protected greater than or equal to 80% of animals challenged with three of the four isolates, and one dose of rifampin protected greater than or equal to 90% challenged with any of the four isolates. Multiple doses of any of the antibiotics prevented endocarditis in greater than or equal to 80% of rabbits challenged with MSSE, and four doses of vancomycin protected rabbits challenged with MRSE. However, MRSE endocarditis was prevented in less than or equal to 25% of animals given six doses of nafcillin or cephalosporins. Thus, nafcillin and cephalosporins were ineffective prophylaxis for MRSE endocarditis, whereas vancomycin, gentamicin, and rifampin were effective.

Animals↗

Prognostic value of teichoic acid antibodies in Staphylococcus aureus bacteremia: a reassessment.

Teichoic acid antibodies were measured in serum using counter immunoelectrophoresis and immunodiffusion technics with a partially purified antigen. Immunodiffusion titers of greather than or equal to 1:4 were obtained in 15/16 patients with S aureus endocarditis but in only two of 122 noninfected individuals and in no patients with endocarditis caused by other gram-positive bacteria. These same elevated titers of antibody were noted in seven of 23 patients with nonendocarditis S aureus infections. These seven patients all had either prolonged, untreated staphylococcal bacteremia or a primary site of infection which was not promptly eradicated. Six of these seven patients responded to four weeks or less of antimicrobial therapy without developing any complications. The development of high titers of teichoic acid antibodies during the course of S aureus bacteremia could not be reliably used to determine the appropriate duration of antistaphylococcal treatment.

Antibodies↗

Antibiotic-resistant Staphylococcus epidermidis in patients undergoing cardiac surgery.

Staphylococcus epidermidis isolates containing subpopulations resistant to 100 microgram of methicillin per ml were found on the chests of only 3 of 80 (4%) patients before cardiac surgery, whereas these highly resistant staphylococci were isolated from the chest wounds of 43 of 80 (54%) patients 5 days postoperatively. The percentage of patients colonized with methicillin-resistant S. epidermidis increased with time postoperatively. Methicillin-resistant postoperative isolates also contained organisms resistant to other antibiotics frequently used during these patients' hospitalizations. The percentages of patients with organisms resistant to various antibiotics were: nafcillin (100%), penicillin (100%), cephalothin (93%), cefamandole (80%), streptomycin (67%), and gentamicin (20%). Preoperative methicillin-susceptible isolates were generally susceptible to other antibiotics. Two patients with S. epidermidis prosthetic valve endocariditis caused by multiple antibiotic-resistant isolates were among the study patients. Antibiotic susceptibility patterns of each isolate from these two patients were identical to those of postoperative chest isolates from the same patient.

Anti-Bacterial Agents↗

Antibiotic therapy of experimental Staphylococcus epidermidis endocarditis.

Endocarditis was produced in rabbits with a methicillin-resistant Staphylococcus epidermidis isolate. Subpopulations resistant to other semisynthetic penicillins and cephalosporins were detected in the isolate. Their presence was probably responsible for the increase in minimum bactericidal concentrations and minimum inhibitory concentrations when tests with high inocula, rather than low inocula were pursued. Rabbits were treated for either 2 or 7 days with nafcillin, cephalothin, cefamandole, vancomycin, rifampin, or gentamicin. Spontaneous death was uncommon in either controls (84% survival) or treated animals (80 to 94% survival). There was no significant difference in the number of bacteria in vegetations of rabbits treated for 7 days with cephalothin, cefamandole, nafcillin, or no antibiotic (control). There was a significant reduction in total bacteria in vegetations of rabbits given vancomycin, gentamicin, or rifampin for 7 days as compared with cephalothin, cefamandole, nafcillin or control. Gentamicin or rifampin sterilized significantly more vegetations after 7 days than cephalothin, cefamandole, nafcillin, or control; rifampin was more effective in sterilizing vegetations than either gentamycin or vancomycin after 2 days. Mutants resistant to 10 mug of rifampin per ml comprised the total bacterial population cultured from vegetations of 2 of 17 rabbits treated with this antibiotic for 7 days; there was no change in the susceptibility of vegetation isolates to other antibiotics. Rifampin, vancomycin, or gentamicin may prove to be more effective in humans than cephalosporins or semisynthetic penicillins in the treatment of methicillin-resistant S. epidermidis endocarditis.

Animals↗

Human infection from an unidentified erythrocyte-associated bacterium.

A 49-year-old splenectomized man had an infection from an unidentified, gram-positive, rod-shaped bacterium that adhered to the majority of his peripheral-blood erythrocytes. On transmission electron microscopy, the bacterium was seen to be extra-erythrocytic and was 0.2 micrometer wide by 1.0 to 1.7 micrometer long. It possessed a thick, granular cell wall, a trilamellar membrane external to the cell wall and prominent mesosomes. Attempts to cultivate the organism in vitro or to duplicate the patient's disease in splenectomized animals were unsuccessful. The patient's response suggested that the bacterium was susceptible to cell-wall-active antibiotics and to chloramphenicol but not to tetracycline. This bacterium may be the cause of other chronic, fever-producing, multisystem diseases of unknown origin.

Animals↗

Effect of type-specific active immunization on the development and progression of experimental Pseudomonas aeruginosa endocarditis.

Rabbits with intracardiac catheters were immunized with heat-killed Pseudomonas aeruginosa or saline and challenged with either 10(9) (high inoculum) or 10(7) (low inoculum) pseudomonas. Immunization did not decrease the incidence of endocarditis when compared with controls, but it did significantly prolong survival. The longer survival of immunized rabbits after high-inoculum challenge was not due to prolongation of the course of endocarditis but to type-specific protection from early, overwhelming bacteremia. However, after low-inoculum challenge there were no early deaths and there was a significantly (P < 0.01) longer survival of immunized (17.4 days) than unimmunized (10.6 days) animals dying of endocarditis. Increased survival was associated with higher total and 2-mercaptoethanol-resistant hemagglutinating antibody titers 1 week after challenge in immunized as compared with unimmunized rabbits. Early (48 h after challenge) vegetation colonization was also significantly (P < 0.05) greater after type-specific as opposed to non-type-specific or saline immunization and low-inoculum challenge. However, whereas 67% of type-specifically immunized rabbits had colonized vegetations at 48 h, only 38.9% died with bacteremic endocarditis. Another 19.2% of immunized rabbits had vegetations colonized with > 10(5) colony-forming units of pseudomonas at elective sacrifice 2 weeks after challenge but no bacteremia; no unimmunized rabbit exhibited similar late colonization. Preexisting antibody may be important in the pathogenesis of pseudomonas endocarditis in drug addicts, and its presence may explain the subacute and often protracted course of the disease.

Animals↗

Rifampin therapy of Staphylococcus epidermidis. Use in infections from indwelling artificial devices.

Rifampin was added to existing antibiotic regimens in two patients with Staphylococcus epidermidis infections; one patient had prosthetic valve endocarditis and the other had an infection of a CSF shunt. The addition of rifampin increased serum or CSF bactericidal titers 16-fold or greater and was correlated with a favorable clinical response. The results of tests for tube-dilution antibiotic susceptibility showed rifampin to be the most active of all antibiotics tested against the patients' organisms. The combinations of gentamicin sulfate, nafcillin sodium, or vancomycin hydrochloride with rifampin prevented the emergence of rifampin resistance in vitro and promoted enhanced killing when compared with either antibiotic alone.

Adolescent↗

Cefamandole kinetics during cardiopulmonary bypass.

The kinetics of cefamandole during cardiac surgery was studied in 16 adult patients given a single intravenous infusion of 20 mg/kg at the time of anesthesia induction. Five normal volunteers who received the same dose served as controls. Cardiopulmonary bypass (CPB) was found to signficantly increase the half-life (t 1/2) of cefamandole. The mean t 1/2 during CPB (113.2 min) was longer than the terminal t 1/2 in normal volunteers (52.0 min; p less than 0.005). Throughout CPB (maximum, 3,7 hr), cefamandole plasma levels were maintained above the minimum inhibitory concentration for those organisms most likely to cause postoperative infections. We conclude that if 20 mg/kg of cefamandole is given within an hour of the beginning of cardiovascular surgery, a supplemental dose is not needed until the patient has been on CPB for at least four hours.

Adult↗

Multiple pneumococcal pyarthrosis complicating rheumatoid arthritis.

Pneumococcal pyarthrosis was documented in seven and ten joints, respectively, in two patients with rheumatoid arthritis. The recognition of multiple pyarthrosis superimposed upon rheumatoid arthritis can be difficult. The present cases are compared with eight previously reported cases of pneumococcal arthritis in patients with rheumatoid arthritis.

Arthritis, Infectious↗

Comparison of cephalothin and cefamandole prophylaxis during insertion of prosthetic heart valves.

Cefamandole nafate (CM) and cephalothin sodium (CP) were administered as prophylaxis in a randomized, prospective study to 30 consecutive patients undergoing prosthetic cardiac valve insertion. A single dose of 20 mg/kg was given intramuscularly during anesthesia induction, and serial plasma antibiotic concentrations, atrial muscle and cardiac valve tissue antibiotic levels, plasma bactericidal activity against pathogenic staphylococci, and infectious complications were determined and compared for the two drugs. Both antibiotics produced high plasma levels (>20 mug/ml 30 min after injection) which fell less than 25% during the period of cardiopulmonary bypass. However, CM levels were significantly higher at most time periods (P<0.05) than CP levels. CP levels were undetectable in atrial muscle from 14 of 15 patients and in valves from 10 of 15 patients. In contrast, CM bioactivity was found in all tissues. Differences in tissue antibiotic concentration could not be accounted for by differences in plasma concentrations or by CP tissue binding and were assumed to be caused by differences in penetration. Plasma bactericidal activity against staphylococci was equal for the two drugs (median titer, 1:16). No infections were seen in either group. CM appeared to be an effective and perhaps preferable prophylactic antibiotic for use during cardiac surgery.

Adolescent↗

Antimicrobial susceptibility and selection of resistance among Staphylococcus epidermidis isolates recovered from patients with infections of indwelling foreign devices.

Twenty-seven isolates of Staphylococcus epidermidis from patients with prosthetic valve endocarditis or infected cerebrospinal fluid shunts were examined for susceptibility to antimicrobial agents. Subpopulations resistant to 20 and 100 mug of methicillin per ml were present in 63% of the isolates (methicillin-resistant isolates). Subpopulations resistant to 20 mug of nafcillin and cephalothin per ml were found in every methicillin-resistant isolate but with frequencies (10(-5.0 +/- 0.5) and 10(-6.4 +/- 0.9), respectively) which were not always detectable by susceptibility testing. Resistance to >/=1.6 mug of penicillin per ml was found in 80% of isolates. Cephalothin, cefazolin, and cefamandole were more active than cefoxitin or cephradine, and gentamicin was more active than tobramycin or amikacin; rifampin was the single most active agent against all isolates. There was no difference in susceptibility between prosthetic valve endocarditis and cerebrospinal fluid shunt infection isolates. Among methicillin-resistant isolates, the phenotypic expression of resistance to methicillin or nafcillin but not to cephalothin could be enhanced by 48 h of incubation with each drug. Isolates containing no methicillin-resistant subpopulations were killed by incubation with methicillin, nafcillin, or cephalothin. High-level resistance to rifampin emerged in both methicillin-resistant and methicillin-sensitive isolates after 8 to 24 h of incubation with this drug. The presence or absence of antibiotic-resistant subpopulations among S. epidermidis isolates and their selection during treatment should be considered when therapy is devised.

Anti-Bacterial Agents↗

RP 59500, a new streptogramin highly active against recent isolates of North American staphylococci.

To assess the potential clinical utility of RP 59500, 10 investigators from separate locations in the United States and Canada each tested approximately 200 current isolates of staphylococci (Staphylococcus aureus and coagulase-negative staphylococci) by a standard protocol. RP 59500 was highly active (MIC90 < or = 2 micrograms/ml) against all strains, including those that were resistant to oxacillin, ciprofloxacin, erythromycin, and spiramycin.

Coagulase↗

Alteration of cutaneous staphylococcal flora as a consequence of antimicrobial prophylaxis.

Antimicrobial agents given as prophylaxis have profound effects on the microbial flora of the skin. Coagulase-negative staphylococci cultured from the skin of patients after cardiac surgery have been found to be more resistant to antimicrobial drugs than organisms cultured from the same skin sites preoperatively. Evidence exists both for the selection of resistant organisms from the preoperative flora and for the postoperative acquisition of such organisms from the nosocomial environment. Staphylococci causing postoperative infections have the same antimicrobial resistance phenotypes as do colonizing isolates; this observation suggests that colonized patients and hospital staff make up a nosocomial reservoir for resistant organisms.

Anti-Bacterial Agents↗

Efficacy of antibiotic combinations including rifampin against methicillin-resistant Staphylococcus epidermidis: in vitro and in vivo studies.

Rifampin in combination with other antibiotics has been used successfully in the treatment of serious infections due to Staphylococcus epidermidis. The authors evaluated the efficacy of rifampin in combination with either cephalothin, nafcillin, gentamicin, or vancomycin to determine in vitro synergistic or antagonistic interactions of the combinations and to determine the role of the second antibiotic in preventing the emergence of rifampin-resistant mutants. The authors found that among 10 isolates of methicillin-resistant S. epidermidis, synergy was found in checkerboard studies (inoculum, 10(5) colony-forming units/ml) for only two isolates and only with nafcillin and rifampin; antagonism was present with one combination for each of four different isolates. Time-kill studies showed each antibiotic capable of preventing the emergence of rifampin-resistant mutants for all 10 isolates, but no synergy or antagonism was present. In experimental endocarditis, however, the addition of cephalothin did not prevent the emergence of rifampin-resistant mutants, and rifampin-resistant mutants were as capable of causing endocarditis as were their rifampin-sensitive parents. Thus, rifampin was a bactericidal antibiotic against methicillin-resistant S. epidermidis. The benefit of a second antibiotic in vitro was the prevention of the emergence of rifampin-resistant mutants. However, in vivo results with a beta-lactam antibiotic did not confirm in vitro observations. More animal and human studies should be performed with antibiotic combinations including rifampin against methicillin-resistant S. epidermidis.

Animals↗

Rifampin treatment of prosthetic valve endocarditis due to Staphylococcus epidermidis.

Twenty-three patients with prosthetic valve endocarditis caused by methicillin-resistant Staphylococcus epidermidis were studied retrospectively for assessment of the role of rifampin treatment. Rifampin (900-1,200 mg daily) was administered in combination with either vancomycin or a beta-lactam antibiotic for an average of 38 days. Eight patients also received an aminoglycoside. Infection was cured in 16 (70%) of these patients; i.e., in 13 (87%) of 15 receiving rifampin plus vancomycin and in three (38%) of eight receiving rifampin plus a beta-lactam antibiotic (P = .025). The addition of rifampin to vancomycin regimens resulted in an increase in serum bactericidal activity. The selection of rifampin-resistant strains of S. epidermidis during treatment with a combination of antibiotics was noted in two patients with persistent infection. The rates of cure obtained with rifampin-beta-lactam combinations were similar to those obtained with beta-lactam agents alone; however, the cure rates obtained with rifampin plus vancomycin (with or without an aminoglycoside) were encouraging and merit further study.

Anti-Bacterial Agents↗