John M. Matsen

Rapid Gentamicin Bioassay Using a Multiple-Antibiotic-Resistant Strain of Klebsiella pneumoniae

A rapid bioassay for gentamicin levels in serum was developed by using a strain of Klebsiella pneumoniae that has multiple resistance to antibiotics. Assays were comparable when performed on either small or large petri plates, and results were available in 2 to 4 h. Studies showed an overall recovery of 97.6% for gentamicin alone or 104.5% in the presence of commonly used antibiotics. The procedure can be performed without the need to inactivate other antibiotics that may be present in the serum sample.

In Vitro Activity, Synergism, and Testing Parameters of Amikacin, with Comparisons to Other Aminoglycoside Antibiotics

The activity of the new aminoglycoside antibiotic, amikacin, was evaluated in vitro against 219 clinical bacterial isolates. One hundred eighty-nine of the 219 strains had agar dilution minimal inhibitory concentration values of 8.0 μg/ml or less for amikacin. Comparative agar dilution studies were performed for gentamicin, kanamycin, and tobramycin. Gentamicin was the most active overall, but tobramycin and amikacin also had significant activity against most bacterial groups. The effects of divalent cations on the susceptibility of Pseudomonas aeruginosa to amikacin were evaluated, and the minimal inhibitory concentration values varied sixfold over a range of divalent cation concentrations from 0.2 to 8.75 mg%. The effects of media and inoculum size on disk susceptibility testing with amikacin were also evaluated. In addition, a synergistic interaction between carbenicillin and amikacin against P. aeruginosa was demonstrated. Amikacin appears to be a promising new broad spectrum antimicrobial agent.

In vitro activities of combinations of aztreonam, ciprofloxacin, and ceftazidime against clinical isolates of Pseudomonas aeruginosa and Pseudomonas cepacia from patients with cystic fibrosis.

The in vitro activities of two-drug combinations of aztreonam, ciprofloxacin, and ceftazidime were studied in 96 clinical isolates of Pseudomonas aeruginosa and in 20 clinical isolates of Pseudomonas cepacia from cystic fibrosis patients. Some synergy was observed with each combination used against P. aeruginosa, but synergy was rare when the combinations were used against P. cepacia.

Comparative activity of cefepime, alone and in combination, against clinical isolates of Pseudomonas aeruginosa and Pseudomonas cepacia from cystic fibrosis patients.

The comparative in vitro activity and synergy of cefepime were evaluated with clinical isolates of Pseudomonas aeruginosa and Pseudomonas cepacia from cystic fibrosis patients. The activity of cefepime, both alone and in combination, was comparable to those of other antibiotics. The clinical efficacy of cefepime in cystic fibrosis patients merits investigation.

Specimen collection and transport

The approach to the collection and transport of meaningful and accurate microbiologic specimens depends upon the nature of the suspected infectious entity and upon the location of the pathogenic process, as well as the possession of appropriate instrumentation and containers. New information and newly developed collection-transport materials have improved the potential for the successful collection and isolation of pathogenic micro-organisms.

Efficacy of aztreonam in pulmonary exacerbations of cystic fibrosis.

A noncomparative pilot study was conducted to assess the potential usefulness of aztreonam in pulmonary exacerbations of cystic fibrosis. Of 27 patients initially enrolled 25 received sufficient courses of aztreonam therapy to be evaluable. All patients received 200 mg/kg/day of aztreonam in 4 equally divided doses administered intravenously. Of 57 isolates of Pseudomonas aeruginosa from pretherapy sputum cultures, 48 were susceptible to aztreonam in vitro as were 11 of 18 strains isolated at the conclusion of therapy. With treatment colony counts of P. aeruginosa in sputum were reduced by 3 log10 or more in 15 patients. It was totally (but temporarily) eradicated in 11 of these patients. Clinical scores and white blood cell counts improved significantly (P less than 0.05). Side effects of aztreonam were limited to transient elevations of liver enzymes occurring in 16 patients. Aztreonam merits further evaluation in a randomized, comparative trial with standard antibiotic therapy for cystic fibrosis.

Changing susceptibility of Pseudomonas aeruginosa isolates from cystic fibrosis patients with the clinical use of newer antibiotics.

To detect a change in antibiotic susceptibility patterns in Pseudomonas aeruginosa isolates upon the introduction and clinical use of ciprofloxacin, aztreonam, and ceftazidime, MICs for clinical isolates collected before introduction of the antibiotics, during early clinical use, and later were determined for these and seven other antipseudomonal antibiotics. Concomitant resistance to two or more antibiotics was also studied. Over the three study periods, rates of susceptibility to 9 of the 10 antibiotics decreased. The largest decrease occurred with ceftazidime. Analysis of subsets of isolates from patients treated with ciprofloxacin or aztreonam also showed declining susceptibility to the latter but a stabilization of susceptibility to the former after an initial decline. Concomitant resistance within and among antibiotic classes was common.

In vitro activity of aztreonam combined with tobramycin and gentamicin against clinical isolates of Pseudomonas aeruginosa and Pseudomonas cepacia from patients with cystic fibrosis.

The in vitro activity of aztreonam combined with tobramycin and with gentamicin was assessed in 78 clinical isolates of Pseudomonas aeruginosa and 11 clinical isolates of Pseudomonas cepacia from patients with cystic fibrosis. Synergy was detected in 56.4% of P. aeruginosa isolates and 60% of P. cepacia isolates with the aztreonam-tobramycin combination and in 49.3% of P. aeruginosa isolates and 81.8% of P. cepacia isolates with the aztreonam-gentamicin combination. No antagonism was observed. These combinations merit clinical evaluation in the treatment of patients with cystic fibrosis.

Comparison and Evaluation of Carbenicillin Disks in Diffusion Susceptibility Testing

A broad variety of bacterial strains, including 79 Pseudomonas aeruginosa, were studied in an in vitro evaluation of carbenicillin disk susceptibility testing. Regression analysis with both 50-μg and 100-μg carbenicillin disks was carried out. Organisms having minimal inhibitory concentration values of 100 to 200 μg/ml demonstrated zones of less than 11 mm with the 50-μg disk, resulting in very little opportunity for appropriate discrimination of results. The line of regression for the 50-μg disk intersected the ordinate at a point just above the minimal inhibitory concentration value considered to be the limit of intermediate susceptibility for Pseudomonas. These considerations, together with evidence of greater disk content variation in the 50-μg than in the 100-μg disks assayed, considerable manufacturer-to-manufacturer variability with the 50-μg disk, and the more appropriate performance of the 100-μg disk, lead us to conclude that the 100-μg disk better serves the clinical test requirements for this agent than does the 50-μg disk, which is currently the only disk available for laboratory testing.

Azlocillin pharmacokinetics in patients with cystic fibrosis.

The pharmacokinetics of azlocillin were studied in 10 cystic fibrosis patients, ranging in age from 11 to 28 years. The patients received a 9- to 23-day course of 350 mg of azlocillin per kg in four or six divided daily doses in combination with am aminoglycoside. Blood and urine samples were collected at specified times after the last dose of the course of azlocillin therapy and then assayed for azlocillin content. Pharmacokinetic parameters were determined by noncompartmental analysis. Mean values for serum half-life (1.74 h), disposition constant (0.41 h-1), total body clearance (123 ml/kg per h), and renal clearance (58 ml/kg per h) were determined. All patients exhibited improvement with respect to clinical and laboratory parameters and displayed no adverse reactions. The pharmacokinetic analysis offers further evidence of the dose-dependent nature of azlocillin elimination, but elimination did not appear to be altered in cystic fibrosis patients.