Biomedical subjects
Publications and source records attributed to J Klastersky.
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Temocillin (BRL 17421) a new penicillin, was compared with cefazolin against 20 strains of Klebsiella. The in vitro minimal bactericidal concentration of cefazolin was twice as active as that of temocillin. Serum bactericidal levels obtained in volunteers treated with temocillin were consistently higher than those levels reached after the administration of cefazolin at the 6-h sampling.
Of 30 patients with predominantly anaerobic localized infections superimposed on chronic tissue damage related to trauma, ischemia, or tumor, 22 (73%) responded satisfactorily to moxalactam therapy. Moxalactam-resistant anaerobic pathogens emerged in two patients and were responsible for treatment failure. In six patients, two of whom also acquired resistant anaerobic pathogens, isolation of moxalactam-resistant aerobic pathogens increased during therapy.
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Hyperthermia has been known since the last century to be effective against cancer, but it has only developed into a new therapeutic method during the past 20 years. The authors review the theoretical and experimental backgrounds of fever therapy and discuss its local and general applications currently under study, including possible synergistic effects with radiotherapy and/or chemotherapy. Particular attention is paid to systemic hyperthermia.
The azlocillin level and killing activity in serum and bronchial secretions against 10 strains of P. aeruginosa were studied in 7 intubated or tracheotomized patients with severe bronchial infection who were receiving the drug as continuous i.v. infusion. In 5 out of 7 patients azlocillin was absent or present only in traces in bronchial secretions in spite of plasma levels ranging between 170 to 340 micrograms/ml. In the other 3 patients azlocillin levels of 23 and 39 micrograms/ml and moderate bactericidal activity against P. aeruginosa could be detected in bronchial secretions. Penicillinase producing strains of Staph. aureus were isolated from the sputum of the 5 patients with extremely low azlocillin level in bronchial secretions. The strain of Staph. aureus isolated from one patient was shown to destroy azlocillin rapidly. In bronchopulmonary infections, Staph. aureus may not only be directly pathogenic but also interfere with the action of beta-lactamase unstable drugs against other microorganisms.
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The findings of a retrospective analysis of 20 patients who developed Gram-negative bacillary meningitis (GNBM) following neurosurgery are reported. The predisposing causes included surgery for skull fracture or cerebral contusion (9 patients), neoplasm (6) and vascular disease (2). Nine of the patients (45 per cent) had a cerebrospinal fluid (CSF) leak from a fistula. The organisms isolated, which included Pseudomonas aeruginosa (6), Klebsiella spp. (5) and Escherichia coli (4), had, in 75 per cent of cases, been isolated from other sites prior to the onset of GNBM. Initial diagnosis was achieved by Gram-stain of CSF in 15 of 19 cases (78 per cent). Culture of lumbar CSF was positive in 19 of the patients (95 per cent) and concommittant ventriculitis was confirmed by positive culture of ventricular CSF in 10 of 11 cases (91 per cent) from whom it was obtained. The overall mortality was 80 per cent, 11 patients dying of causes directly related to GNBM. Eradication of the infecting organism from CSF was achieved in 79 per cent of patients receiving intraventricular aminoglycoside therapy, but in only 40 per cent of those receiving intralumbar therapy. Deaths in the latter group were associated with ventriculitis whereas those in patients receiving intraventricular therapy resulted from intracranial abscess formation. These findings, plus the observation of chloramphenicol resistance in 80 per cent of the isolates, suggest that systemic and intraventricular aminoglycoside administration is indicated in patients with post-neurosurgical GNBM.
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The bactericidal activity of rifampin plus other antibiotics was examined with in vitro checkerboard dilutions against 15 strains of staphylococci, with time-kill studies, and with determinations of serum bactericidal activities (SBAs) in volunteers. In vitro synergism was found consistently only in inhibitory assays with rifampin plus minocycline. Time-kill studies with rifampin plus methicillin revealed enhanced killing at concentrations close to the MBC but reduced combined activity at higher concentrations. SBAs with rifampin, oxacillin, and the two drugs in combination were studied in three treatment regimens (regimen A: 2 g of oxacillin and 300 mg of rifampin; regimen B: 1 g of oxacillin and 450 mg of rifampin; and regimen C: 3 g of oxacillin and 450 mg of rifampin). The SBA against methicillin-sensitive Staphylococcus aureus was significantly lower with the two drugs in combination than with oxacillin alone in regimen A but not in regimen B. In vitro synergy with rifampin plus other antibiotics was not frequent. At high concentrations, the bactericidal activity of oxacillin was reduced by rifampin, but killing activity may be enhanced at low concentrations of oxacillin.
An in vitro model is described that simulates serum and tissue levels of antibiotic, allowing the exposure of bacteria to changing concentrations of antibiotic with little dilution of the inoculum. A bacterial suspension is placed in the outer chamber of a unit through which runs a bundle of 150 polysulfone hollow fibers that retain proteins of greater than 10,000 daltons. These "capillaries" are in contact with the tubular lumen of a perfusion system. Antibiotic is injected into the tubing and circulated by a pump. At desired intervals given volumes of perfusate are removed and replaced with antibiotic-free broth (resulting in decreasing drug concentrations), or a constant level can be maintained. Samples from the outer chamber are taken for determination of bacterial counts and antibiotic levels. This method allows for the in vitro determination of persistent antibiotic effects and comparison of bolus and continuous infusions as well as the effects of single or combined antibodies on bacterial killing and regrowth.
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