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Biomedical subjects

H F Chambers

Publications and source records attributed to H F Chambers.

At least 73 records · Page 4Linked to original sources
PubMed1988

Methicillin-resistant staphylococci.

Strains of staphylococci resistant to methicillin were identified immediately after introduction of this drug. Methicillin-resistant strains have unusual properties, the most notable of which is extreme variability in expression of the resistance trait. The conditions associated with this heterogeneous expression of resistance are described. Methicillin resistance is associated with production of a unique penicillin-binding protein (PBP), 2a, which is bound and inactivated only at high concentrations of beta-lactam antibiotics. PBP2a appears to be encoded by the mec determinant, which also is unique to methicillin-resistant strains. The relationships between PBP2a and expression of resistance and implications for the mechanism of resistance are discussed. The heterogeneous expression of methicillin resistance by staphylococci poses problems in the detection of resistant strains. Experience with several susceptibility test methods is reviewed and guidelines for performance of these tests are given. Treatment of infections caused by methicillin-resistant staphylococci is discussed. Vancomycin is the treatment of choice. Alternatives have been few because methicillin-resistant strains often are resistant to multiple antibiotics in addition to beta-lactam antibiotics. New agents which are active against methicillin-resistant staphylococci are becoming available, and their potential role in treatment is discussed.

Bacteriological Techniques↗
PubMed1987

Risk of transmitting the human immunodeficiency virus, cytomegalovirus, and hepatitis B virus to health care workers exposed to patients with AIDS and AIDS-related conditions.

This prospective cohort study was designed to evaluate the risk of occupational transmission of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and cytomegalovirus (CMV) to health care workers with intensive exposure to HIV-infected patients. Seventy-five percent of the 270 subjects had been exposed to patients with AIDS and AIDS-related conditions (ARC) for at least one year before enrollment, 18% worked in specialized AIDS units, and 35% sustained a total of 342 accidental parenteral exposures to HIV-infected body fluids. At the time of enrollment, none had antibody to HIV, and none of the 175 subjects retested 10 months later had acquired antibody. No evidence of increased risk of acquiring CMV or HBV was obtained. These results indicate that health care workers are at minimal risk for HIV, CMV, and HBV transmission from occupational exposure to patients with AIDS or ARC, even when intensively exposed for prolonged periods of time.

AIDS-Related Complex↗
PubMed1987

Comparative activity of CGP 31608, nafcillin, cefamandole, imipenem, and vancomycin against methicillin-susceptible and methicillin-resistant staphylococci.

The activity of CGP 31608 for 53 strains of Staphylococcus aureus and 48 strains of S. epidermidis, both methicillin susceptible and resistant, was compared with that of vancomycin, nafcillin, cefamandole, and imipenem. Microdilution MICs were determined in Mueller-Hinton broth with or without 2.5% NaCl at an inoculum of 3 x 10(5) CFU/ml with a 20-h, 37 degrees C incubation. The MICs of imipenem and CGP 31608 for methicillin-resistant strains were lower than the MICs of nafcillin or cefamandole for these strains; these differences diminished in the presence of 2.5% NaCl. Subpopulations were detected in strains of methicillin-resistant S. aureus and S. epidermidis that were resistant to all the beta-lactam antibiotics tested at 5 micrograms/ml. This resistant subpopulation produced progeny that were uniformly resistant to high concentrations of each of the beta-lactams.

Anti-Bacterial Agents↗
PubMed1987

Coagulase-negative staphylococci resistant to beta-lactam antibiotics in vivo produce penicillin-binding protein 2a.

Strains of coagulase-negative staphylococci were tested for in vivo resistance in a rabbit model of prophylaxis of endocarditis. Regimens of nafcillin, cefazolin, cefamandole, and vancomycin were compared for efficacy in the prevention of infection caused by two methicillin-resistant strains and a susceptible strain. For the two resistant strains, vancomycin was the most effective drug tested. All regimens were effective against the susceptible strain. The two strains for which prophylaxis with beta-lactam antibiotics failed produced a beta-lactam antibiotic-inducible penicillin-binding protein (PBP) that comigrated in sodium dodecyl sulfate-polyacrylamide gels with the low-affinity PBP 2a that is associated with methicillin resistance in strains of Staphylococcus aureus. Like PBP 2a, this PBP had low binding affinity for beta-lactam antibiotics. Peptide maps after either V8 protease or chymotrypsin digestion of radiolabeled PBP 2a or silver-stained preparations were virtually identical to one another and to maps of PBP 2a from a heterogeneous and a homogeneous strain of S. aureus. Methicillin resistance in coagulase-negative staphylococci and therapeutic failure with beta-lactam antibiotics in vivo is associated with production of PBP 2a, which appears to be highly conserved structurally among different species of staphylococci.

Animals↗
PubMed1987

Effect of NaCl and nafcillin on penicillin-binding protein 2a and heterogeneous expression of methicillin resistance in Staphylococcus aureus.

Expression of methicillin resistance in heterogeneous strains of Staphylococcus aureus is enhanced by 2 to 5% NaCl in the medium and by selection with beta-lactam antibiotics. Resistance is associated with production of a penicillin-binding protein (PBP), PBP 2a, with low affinity for binding beta-lactam antibiotics. Therefore, the effects of NaCl and nafcillin on amounts of PBP 2a produced and its binding affinity were examined and correlated with expression of resistance. Nafcillin-triggered autolysis also was examined. No relationships between the level of resistance expressed and (i) relative amounts of PBP 2a, (ii) inducibility of PBP 2a by nafcillin, or (iii) binding affinity of nafcillin for PBP 2a were found. A protective effect of NaCl for the susceptible subpopulation, corresponding to inhibition of autolysis, was observed for heterogeneous strains. Even in the absence of NaCl, highly resistant cells were relatively tolerant to nafcillin-triggered autolysis. These results support the hypothesis that high levels of resistance require an additional factor besides PBP 2a. This factor may act within the autolytic pathway.

Bacterial Outer Membrane Proteins↗
PubMed1987

Cocaine use and the risk for endocarditis in intravenous drug users.

Endocarditis is a relatively frequent infection in intravenous drug users. We compared features in the cases of 102 patients with those in intravenous drug users with other causes of fever to identify risk factors predictive of endocarditis. Logistic regression analysis showed cocaine use to be strongly associated with endocarditis. This special risk involving cocaine use has not been reported previously; the explanation for it may provide insight into the pathogenesis of endocarditis.

Adult↗
PubMed1986

Serum bactericidal titer as a predictor of outcome in endocarditis.

A study was conducted in 89 rabbits with experimental aortic valve endocarditis caused by three different strains of Staphylococcus aureus to determine whether there was a correlation between the peak serum bactericidal titer of the four drugs tested and the vegetation titer. After four days of therapy both the rabbits with and those without sterile vegetations had median peak bactericidal titers of 1 : 8. The mean vegetation titers did not correlate with the mean bactericidal titers. The serum bactericidal test does not measure the relative rate of killing of the bacteria by the drugs. Although the test remains clinically useful for documentation of bactericidal activity, the minimum level of activity necessary for the test to serve as a predictor of outcome remains to be defined.

Animals↗
PubMed1986

Ciprofloxacin in experimental Pseudomonas aeruginosa meningitis in rabbits.

The potential of ciprofloxacin for the therapy of Pseudomonas aeruginosa meningitis was evaluated in an animal model by determining the penetration of the drug into CSF, its concentration-dependent killing characteristics in vivo, and its relative efficacy compared with ceftazidime and tobramycin. Meningitis was produced in 40 rabbits by intracisternal injection of 3 X 10(7) organisms. The drugs were administered intravenously over seven hours, and simultaneously serum and CSF samples were taken at 0, 1, 3, 5, and 7 h for determination of drug concentration and CSF bacterial counts. The percentage penetration of ciprofloxacin (18.4 +/- 12.3; mean +/- standard deviation) in infected rabbits was substantially increased over that found in uninfected rabbits (4.1 +/- 1.3). The rate of bacterial killing for animals treated with ceftazidime (100 mg/kg/h) and high doses of tobramycin (2.5 mg/kg/h) was -0.51 +/- 0.13 (log10 cfu/ml/h). This was similar to the rate of killing (-0.48 +/- 0.2) found when ciprofloxacin was infused at 5 mg/kg/h, a dose that produced a mean serum level of 6.7 +/- 4.6 mg/l, which corresponds to concentrations achievable in humans. As dosages were increased (15 and 30 mg/kg/h), the rate of bacterial killing also increased (-0.70 +/- 0.1 and -0.89 +/- 0.4 respectively; r = 0.7407; P less than 0.01). The drugs shows promise in the treatment of pseudomonas meningitis.

Animals↗
PubMed1986

Serum bactericidal activity of rifampin in combination with other antimicrobial agents against Staphylococcus aureus.

Because rifampin-resistant strains of Staphylococcus aureus emerge during monotherapy with this drug, a search was made for potentially useful companion drugs. Bactericidal titers of spiked serum were determined, and time kill studies were performed for 10 strains of methicillin-susceptible S. aureus. We tested rifampin in combination with nafcillin, vancomycin, clindamycin, pefloxacin, ciprofloxacin, trimethoprim, teicoplanin, or erythromycin. The bactericidal activity of nafcillin, vancomycin, and teicoplanin was significantly reduced (P less than 0.05) when rifampin was added to the drug regimen. In contrast, the addition of rifampin to clindamycin or erythromycin significantly increased bactericidal activity as measured by both bactericidal titers in serum and 6-h killing rates (P less than 0.02). Bactericidal activity in serum was also increased by the addition of rifampin to trimethoprim, but rifampin-resistant strains emerged with this combination.

Anti-Bacterial Agents↗
PubMed1986

Efficacy of ciprofloxacin for experimental endocarditis caused by methicillin-susceptible or -resistant strains of Staphylococcus aureus.

The efficacy of ciprofloxacin for experimental aortic valve endocarditis in rabbits infected by either a methicillin-susceptible or a methicillin-resistant strain of Staphylococcus aureus was compared with standard therapy of nafcillin or vancomycin, respectively. After 4 days of therapy, ciprofloxacin reduced the counts of organisms in aortic valve vegetations as effectively as the standard regimen for both susceptible and resistant strains. Mean concentrations of ciprofloxacin in serum achieved 1 h after a dose exceeded the MBC for each strain by twofold or less. In these experiments ciprofloxacin was as efficacious as standard regimens currently used to treat staphylococcal infections in humans.

Animals↗
PubMed1985

Pefloxacin therapy for experimental endocarditis caused by methicillin-susceptible or methicillin-resistant strains of Staphylococcus aureus.

The therapeutic efficacy of pefloxacin in experimental endocarditis caused by methicillin-susceptible or methicillin-resistant Staphylococcus aureus was evaluated. In rabbits infected with a methicillin-susceptible strain, 4 days of pefloxacin therapy significantly reduced both the number of bacteria per gram of vegetation and the mortality rate compared with untreated controls, and pefloxacin was equivalent to cephalothin. Pefloxacin was also as effective as vancomycin in reducing vegetation titers and mortality rate in animals with endocarditis caused by a methicillin-resistant strain. These results suggest that pefloxacin may be an effective agent in the therapy of serious infections caused by either methicillin-susceptible or -resistant strains of S. aureus.

Animals↗
PubMed1985

Increased amounts of a novel penicillin-binding protein in a strain of methicillin-resistant Staphylococcus aureus exposed to nafcillin.

In addition to the four typical penicillin-binding proteins (PBPs), a strain of heterogeneously methicillin-resistant Staphylococcus aureus produced an extra 78-kD PBP (PBP 2a) that had a low affinity for nafcillin and penicillin. Addition of nafcillin to cultures of this strain caused a rapid increase in the amount of this PBP in cell membranes. This increase occurred at subinhibitory concentrations of drug within minutes of exposure, and was blocked by inhibitors of protein and RNA synthesis. This suggests that the synthesis of PBP 2a can be stimulated by exposure to beta-lactam antibiotics. This process may, in part, explain the heterogeneity in methicillin-resistant S. aureus.

Bacterial Proteins↗
PubMed1985

Hemodynamic characteristics of patients with hypothermia due to occult infection and other causes.

Eighty-five consecutive patients with hypothermia were prospectively evaluated to assess clinical and laboratory data that would differentiate those patients with hypothermia caused by severe infection and bacteremia and those with hypothermia of other causes. Thirty-two patients had hemodynamic monitoring, allowing us to assess hemodynamic differences between the two groups. Clinical characteristics, including admission temperature, leukocyte count, mean arterial pressure, pulse rate, respiratory rate, arterial pH, and pulmonary capillary wedge pressure, did not distinguish between the two groups. However, patients with infection with bacteremia had lower calculated systemic vascular resistances (486.0 +/- 125.0 compared with 1759.9 +/- 331.0 dynes.s.cm-5; p = 0.001) and higher cardiac indices (7.1 +/- 1.9 compared with 2.8 +/- 0.7 L/min X M2; p = 0.006) than patients without severe infections. Thus, our data suggest that hemodynamic characteristics are different in patients with infection-related hypothermia and patients with hypothermia associated with other causes, and appear to depend on the underlying disease.

Adult↗
PubMed1984

Endocarditis due to methicillin-resistant Staphylococcus aureus in rabbits: expression of resistance to beta-lactam antibiotics in vivo and in vitro.

Whether a strain of methicillin-resistant Staphylococcus aureus susceptible to cephalothin by the disk-diffusion method was also susceptible to cephalothin in vivo was evaluated in the rabbit model of endocarditis. Rabbits with aortic-valve endocarditis due to methicillin-resistant S. aureus that were treated for four days with cephalothin had the same numbers of organisms in vegetations as did untreated rabbits. Treatment with cephalothin caused emergence of a highly resistant subpopulation in aortic-valve vegetations. Organisms highly resistant to cephalothin were also highly resistant to nafcillin. Thus broth-dilution and disk-diffusion tests may not predict therapeutic failure for cephalothin against strains of methicillin-resistant S. aureus. Because of cross-resistances among beta-lactam drugs, these strains should be considered uniformly resistant to this general class of antimicrobial agents, regardless of results from these tests.

Animals↗
PubMed1984

Teicoplanin versus nafcillin and vancomycin in the treatment of experimental endocarditis caused by methicillin-susceptible or -resistant Staphylococcus aureus.

In rabbits with experimentally induced endocarditis, the efficacy of teicoplanin compared favorably both with that of nafcillin for infection by a methicillin-susceptible strain of Staphylococcus aureus and with that of vancomycin for infection by a methicillin-resistant strain of S. aureus. In a 4-day treatment regimen, teicoplanin was as effective as either nafcillin or vancomycin in eliminating organisms from aortic valve vegetations in the respective infection. In a 10-day regimen for methicillin-resistant S. aureus endocarditis, both teicoplanin and vancomycin sterilized the vegetations of some rabbits, but the relapse rate was high for both. These results justify further investigation into the role of teicoplanin for the treatment of serious infections caused by S. aureus.

Animals↗
PubMed1983

Staphylococcus aureus endocarditis: clinical manifestations in addicts and nonaddicts.

Data collected from a prospective multicenter study of endocarditis caused by S. aureus were analyzed to contrast the clinical presentation of the disease between a group of 46 intravenous drug addicts and a group of 35 nonaddicts. Two-thirds of the patients in each group were men. The duration of illness before diagnosis was similar (mean, 9.3 days). Intravenous-drug addicts were younger and had less underlying disease (30% versus 80%) than the non-addicts. When first seen, the drug addicts had signs and symptoms of sepsis and pulmonary embolism, but only 40% had pathologic murmurs. Seventy-six percent had evidence of tricuspid valve infection only. Congestive heart failure and neurologic manifestations were uncommon in addicts. Nonaddicts had infection involving predominantly the left side of the heart (14 mitral valves, 8 aortic valves, 4 both aortic and mitral valves) and 80% had underlying medical diseases. Only half of these patients had pathologic murmurs when first examined, but another 30% developed them later. Congestive heart failure, involvement of the central nervous system, and peripheral embolic or septic complications each occurred in over half of the nonaddicts. Eighty percent of these patients had peripheral stigmas of endocarditis. One intravenous drug addict (2%) and seven nonaddicts (20%) died. Six patients required cardiac valve replacement either during or after a course of antibiotics. Outcome was not related to the titer of peak serum bactericidal tests. Endocarditis caused by S. aureus presents as two distinct clinical syndromes depending on the patient population (intravenous drug user or nonaddict) and the location of infection (right-sided or left-sided). The disease is distinguished from endocarditis due to other causes by its acute onset and its fulminant course manifested by a multitude of septic and embolic complications and its ability to cause heart failure. Medical management alone is often successful but in certain subsets of patients, notably those with infection of aortic or multiple valves, early operation may be necessary.

Endocarditis, Bacterial↗
PubMedDate not supplied

Failure of a once-daily regimen of cefonicid for treatment of endocarditis due to Staphylococcus aureus.

Cefonicid, a new long-acting cephalosporin, was evaluated for treatment of endocarditis due to Staphylococcus aureus. Four patients, all with infection of the tricuspid valve, were treated with a single daily injection. By the fifth day of therapy, three of the four patients continued to have spiking fevers and positive blood cultures, and treatment with cefonicid was discontinued. Even though peak concentrations of antibiotic in serum were greater than 20-40 times the minimum inhibitory concentration of the antibiotic for the infecting organism, serum bactericidal titers were less than 1:8 in three patients. Susceptibility testing of 52 clinical isolates in broth confirmed a marked difference between inhibitory and bactericidal concentrations for 40% of these strains. In addition, susceptibility testing performed in serum rather than broth resulted in a sixfold increase in the minimum inhibitory concentration, a result suggesting that protein binding may be in part responsible for these failures of treatment. Cefonicid administered as a single daily dose is inadequate for treatment of endocarditis due to S. aureus and should not be used for treatment of bacteremia or life-threatening infections known or suspected to be caused by this organism.

Adult↗