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PubMed1990

Adaptive resistance to aminoglycoside antibiotics from first-exposure down-regulation.

Adaptive resistance to the bactericidal effect of an aminoglycoside antibiotic was induced in Pseudomonas aeruginosa and other aerobic gram-negative bacilli by initial exposure to the drug. Both subinhibitory and inhibitory concentrations produced resistance in bacterial cells surviving the effects of the initial ionic binding. Development of drug refractoriness required an adaptive period of growth, was enhanced by the continued presence of drug, and reversed after several hours of growth in drug-free medium. Unstable resistance was not explained by selection of mutants. The mechanism of adaptive resistance was down-regulation of aminoglycoside uptake during the period of accelerated energy dependent drug transport (EDP II). Down-regulation induced by gentamicin or tobramycin produced cross-resistance to other aminoglycosides. The kinetics of unstable first-exposure resistance suggests that a continuous drug level might not provide the most effective therapy with aminoglycosides and gives rationale to larger initial and longer interval bolus dosing.

Anti-Bacterial Agents↗
PubMed1991

Immunization of mice with antibiotic-treated Escherichia coli results in enhanced protection against challenge with homologous and heterologous bacteria.

The murine immune response to Escherichia coli exposed to subminimal inhibitory concentrations of four antibiotics was investigated. Groups of mice were injected for 8 weeks with formalin-killed bacteria and subsequently challenged with 10 x LD50 of viable E. coli. Mice receiving saline only (controls) died within 24 h. The mortality of mice immunized with ciprofloxacin-treated E. coli was significantly lower than that of mice immunized with E. coli untreated or treated with other antibiotics. Sera from mice immunized with ciprofloxacin-treated bacteria showed better bacteriostatic capacity and enhanced production of antibodies that bound to homologous and heterologous lipopolysaccharide isolated from several smooth and rough gram-negative strains. The better protection observed in mice immunized with ciprofloxacin-treated E. coli was probably due to an enhanced production of antibodies to epitopes on lipopolysaccharide that became better exposed and so more accessible after treatment with ciprofloxacin.

Animals↗
PubMed1986

In-vitro studies of antibiotic combinations with special emphasis on the evaluation of newly developed methods.

We have described an in-vitro pharmacokinetic model that mimics the serum and tissue concentrations of antibiotics during therapy of human patients, and thus presents a changing concentration of antibiotics to the bacterial inoculum. This pharmacokinetic model has been used to study antibiotic combinations that are used in the treatment of infections in granulocytopenic patients. In this model the addition of piperacillin to amikacin or of ceftazidime or azlocillin to another aminoglycoside prevented the regrowth of resistant subpopulations of Pseudomonas aeruginosa. The activities of several antibiotic combinations were studied in the in-vitro model, the conventional checker-board method and the time-kill method. Discrepant results were found with the model and the conventional tests in one-third of the combinations. The model may be useful in the preclinical study of antibiotic combinations and may be proved more predictive of clinical outcome than conventional tests.

Amikacin↗
PubMed1988

In-vitro teicoplanin-resistance in coagulase-negative staphylococci from patients with endocarditis and from a cardiac surgery unit.

Among 31 strains of coagulase-negative staphylococcus (CNS) causing endocarditis in individual patients, 16 had MIC of teicoplanin greater than or equal to 8 mg/l (MIC50, 8; MIC90, 8; MIC range, 0.5-32 mg/l); and 24 had MBC greater than or equal to 16 mg/l (MBC50, 32; MBC90, 64; MBC range, 4-128 mg/l). Greater sensitivity was shown to vancomycin (MIC50, 2; MIC90, 4; MIC range, 1-8 mg/l; MBC50, 2; MBC90, 4; MBC range, 0.5-8 mg/l). Teicoplanin-resistant CNS (MIC, greater than or equal to 8 mg/l) were detected in the anterior nares of two of three patients and six of nine staff, and in the air, of a cardiac surgery unit, and in other series of CNS of clinical origin. The results of in-vitro sensitivity testing of CNS to teicoplanin are dependent on the media and conditions used, and their clinical significance has not been determined. Nevertheless, the findings reported here put in question the use of teicoplanin alone as prophylaxis during valve replacement surgery.

Cardiac Surgical Procedures↗
PubMed1992

Extensive hepatic necrosis in a premature infant.

A fatal case of fulminant hepatic failure that occurred in the neonatal period is reported in a premature infant born after 27 4/7-weeks' gestation. Immediately after birth the infant had severe hypoxia and hypotension resulting from birth asphyxia, hypovolemic shock, and septicemia. At autopsy, histological appearance of the liver showed virtually total hepatocellular necrosis without features of fibrosis. Although the exact cause of hepatocellular injury cannot be fully ascertained, it is assumed that hypoxia and hypotension must have been the predominant factors leading to massive hepatic necrosis.

Acyclovir↗
PubMed1987

Clinical pharmacokinetics, toxicity and cost effectiveness analysis of aminoglycosides and aminoglycoside dosing services.

This article reviews the clinical pharmacokinetics, clinical toxicity and cost-effectiveness analysis of aminoglycosides and of dosing services for aminoglycosides. The reader is referred elsewhere for a review of the pharmacology, antimicrobial spectrum of activity and clinical use of these drugs. A critique of the more commonly used methods of aminoglycoside dosage determinations is included, based on the inter-individual variation in aminoglycoside disposition parameters. The advantages and disadvantages of arbitrary, predictive, and pharmacokinetic methods of dosing determination are summarized. Justification for the routine determination of serum aminoglycoside concentrations is reviewed. We review the lack of standardization of definitions for aminoglycoside-associated nephrotoxicity in published studies, and studies which illustrate these differences are highlighted. Evidence for the association between serum aminoglycoside concentrations and nephrotoxicity is examined. Ototoxicity is similarly reviewed. The concept of cost-effectiveness analysis is examined extensively in this review. We discuss the literature concerning the cost benefit analysis of drug dosing services.

Amikacin↗
PubMed1992

Gingival status during chemical plaque control with or without prior mechanical plaque removal in patients with acute myeloid leukaemia.

The purpose of the study was to evaluate the effect of a mouthrinse regimen comprising both chemical plaque control and mechanical plaque removal. 20 adult patients with acute myeloid leukaemia were assigned to one of the following 2 regimens: (1) (group 1) mouthrinse twice daily with a 0.1% chlorhexidine solution; or (2) (group 2) the same regimen, but preceded by mechanical removal of plaque and calculus on day 1. All patients were followed for 28 days from the initiation of remission-induction therapy. In group 2, the plaque scores remained lower than those of group 1 throughout the study, although only 3 patients remained completely free of plaque after 28 days. Gingival inflammation as judged by bleeding scores remained unchanged in group 1, whereas in group 2, the degree of inflammation was reduced from 52% (median value) on day 1 to 31% (median value) on day 28. The bleeding scores were also lower in group 2 (31%) than in group 1 (60%) on day 28. No differences were found between the 2 groups with respect to the occurrence of other oral infections. It is concluded that chemical plaque control with chlorhexidine should be preceded by mechanical removal of plaque and calculus, when used in patients with acute myeloid leukaemia and thrombocytopenia.

Aclarubicin↗
PubMed1989

Further studies on post-antibiotic effect and synergism in two strains of Streptococcus faecalis.

The differences in the synergistic potential for either killing effect or increase in duration of post-antibiotic effect (PAE) seen with various beta-lactam-aminoglycoside combinations in two strains of Streptococcus faecalis were further studied to examine this relationship in more detail. It was seen that a strain which produced a synergistic increase in recovery period (PAE greater than or equal to 0.5 h), comparing the beta-lactam antibiotics alone and when combined with streptomycin, showed increased sensitivity (greater than or equal to 1 log10 reduction in viable counts) to a subinhibitory concentration of streptomycin added to a culture recovering from the PAE; this was not demonstrated with a strain showing no increase in PAE when briefly exposed to a combination therapy, although its corresponding killing curve was clearly synergistic. Moreover, it was seen that the differences in the synergistic prolongation of recovery period when combining various aminoglycosides at 1/4 x MIC with ampicillin were consistent with the different duration of PAE with the particular aminoglycoside alone at the MIC.

Ampicillin↗
PubMed1994

[A case of MRSA sepsis treated by the sequential combination therapy netilmycin and minocycline].

A sixteen year old female was feverish from June 12, 1993. Methicillin-resistant Staphylococcus aureus was isolated from the blood, the diagnosis of MRSA sepsis was established. Vancomycin (2 g/day) was administered for eighteen days, but MRSA was not eradicated in the blood culture. Then she was administered a combination therapy of arbekacin (200 mg/day) and imipenem/cilastain (1 g/day) for seven days, but MRSA in the blood was cultured continuously. The sequential combination therapy of netilmycin (200 mg/day) and minocycline (200 mg/day) was started, MRSA was eradicated from the blood culture after four days. The sequential combination therapy netilmycin and minocycline was seemed to be effective for MRSA infection.

Adolescent↗
PubMed1983

Gentamicin substrate-labeled fluorescent immunoassay containing monoclonal antibody.

The current substrate-labeled fluorescent immunoassay for gentamicin has been modified by substituting monoclonal antibodies for conventional antiserum to gentamicin. The standard curve generated with gentamicin monoclonal antibody was essentially linear from 0 to 12 micrograms/ml, could detect 0.4 micrograms of gentamicin per ml, and had overall intra- and interassay precision values (coefficients of variation) of 1.9 and 5.0%, respectively. The substrate-labeled fluorescent immunoassay produced with gentamicin monoclonal antibody gave results with clinical specimens comparable (r = 0.991) to those obtained with the commercially available substrate-labeled fluorescent immunoassay and also with an enzyme immunoassay, a radioimmunoassay, and a fluorescent immunoassay. This technologically state-of-the-art assay employs both a nonisotopic label and monoclonal antibodies. It offers excellent precision, sensitivity, lot-to-lot reproducibility, linearity, and reagent stability.

Antibodies, Monoclonal↗