John A. Bosso

The Comparative In Vitro Activity of Ofloxacin and Selected Ophthalmic Antimicrobial Agents Against Ocular Bacterial Isolates

The in vitro activity of ofloxacin, a new fluoroquinolone anti-infective agent, was evaluated against 419 ocular bacterial isolates of 55 species to determine its potential as a topical agent for the treatment of ocular infections. Other agents tested in this study, in which a modified tube-dilution procedure was used, include norfloxacin, gentamicin, tobramycin, chloramphenicol, and polymyxin B. Ofloxacin demonstrated good to excellent activity against a variety of gram-positive and gram-negative pathogens. The minimum inhibitory concentration against 90% of all bacterial strains tested (MIC90) of ofloxacin was 0.5 microgram/ml for Staphylococcus aureus and S. epidermidis, 2 micrograms/ml for Streptococcus pneumoniae, and 4 micrograms/ml for Pseudomonas aeruginosa. These species were more susceptible to ofloxacin than to any of the nonquinolones tested. The MIC90 of ofloxacin was lower than that of norfloxacin, another quinolone, against S. aureus, S. epidermidis, and St. pneumoniae and equal to that of norfloxacin against P. aeruginosa. Because of its broad spectrum of activity and excellent in vitro activity, we concluded that ofloxacin has the potential for development into a superior topical treatment for ocular infection.

Clinical manifestations of exacerbations of cystic fibrosis associated with nonbacterial infections.

The purpose of this study was to determine whether acute pulmonary exacerbations of cystic fibrosis associated with nonbacterial infections are clinically distinguishable from other exacerbations. Eighty exacerbations in 54 patients were studied. Exacerbations associated with influenza (n=8) were compared with those associated with other nonbacterial infections (n=15) and those in which no nonbacterial infection was detected (n=57). Patients with influenza had lower Shwachman scores and were more likely to be seroposifive for C-reactive protein than patients in the other two groups. Patients with influenza had lower Shwachman scores and were more likely to be seropositive for C-reactive protein than patients in the other two groups. Patients with influenza had a mean decrease in forced expiratory volume per second of 26%, compared with test results obtained before the exacerbation. In contrast, the mean decrease in forced expiratory volume per second was 6% for other nonbacterial infections and 12% for the group without nonbacterial infection (p<0.05 for both comparisons). The forced expiratory flow in first 25% of vital capacity decreased 44% in the influenza group compared with 13% and 17% in the other two groups, respectively (p<0.01 for both comparisons). The influenza group also had a higher proportion of patients with at least a 20% decrease in forced expiratory volume per second and forced expiratory flow in first 25% of vital capacity than the other two groups had (p<0.05 for all comparisons). These data suggest that influenza is associated with severe exacerbations in patients with cystic fibrosis and support recommendations for efforts to prevent influenza in this population.

Cefoperazone pharmacokinetics in preterm infants.

The elimination pharmacokinetics of cefoperazone, a new cephalosporin, were studied in 15 preterm infants ranging in gestational age from 32 to 36 weeks and in postnatal age from 1 to 6 days. The infants received a single dose of either 50 or 250 mg of cefoperazone per kg by intravenous infusion. Blood samples were collected at specified times after completion of the drug infusion and then assayed for cefoperazone. Pharmacokinetic parameters were determined by noncompartmental analysis. Mean values for plasma half-life, elimination rate constant, apparent steady-state volume of distribution, and total body clearance were 5.53 h, 0.15 h-1, 124 ml/kg, and 36 ml/h per kg, respectively, for the group receiving a 50-mg/kg dose and 5.76 h, 0.14 h-1, 111 ml/kg, and 35 ml/h per kg, respectively, for the group receiving a 250-mg/kg dose. Positive correlations between gestational age and clearance and elimination rate were detected. A 50-mg/kg dose every 12 h ensured adequate serum levels for most of the common neonatal pathogens. Other than a transient rise in eosinophils in four subjects, no adverse effects were noted.

Bacterial resistance to antibiotics: mechanisms and prevalence in hospitals and nursing homes

Bacterial resistance to antibiotics has become an increasingly distressing problem over the last few decades. In this article, known resistance mechanisms are reviewed and the extent of the problem in both hospitals and nursing homes is addressed. Suggestions for preventing the further spread of this problem are presented.

Compatibility and Stability of Clindamycin Phosphate-Aminoglycoside Combinations Within Polypropylene Syringes

The stability and compatibility of clindamycin phosphate admixed separately with gentamicin sulfate, tobramycin sulfate, and amikacin sulfate in polypropylene syringes under specific storage conditions were studied. In duplicate syringes, clindamycin phosphate 900 mg was admixed with sterile NaCl 0.9% 1 ml and with either gentamicin sulfate 120 mg, tobramycin sulfate 120 mg, or amikacin sulfate 750 mg. In duplicate polypropylene syringes, control solutions of clindamycin phosphate and each aminoglycoside were prepared separately and stored under the same conditions. The clindamycin control consisted of clindamycin phosphate 900 mg in 6 ml. The gentamicin and tobramycin controls consisted of gentamicin sulfate and tobramycin sulfate 120 mg in 3 ml plus 1 ml of sterile NaCl 0.9%. The amikacin control consisted of amikacin sulfate 750 mg in 3 ml plus 1 ml of sterile NaCl 0.9%. Drug concentrations were determined at the time of preparation and 1, 4, 8, 12, 24, and 48 hours thereafter. Aminoglycosides were assayed by fluorescence polarization immunoassay and clindamycin was assayed by high performance liquid chromatography. Visual inspections and pH determinations of each combination and control solution were performed at each assay time. For the clindamycin, gentamicin, tobramycin, and amikacin control solutions, changes in concentration were within ten percent of the original concentration. Concentrations of clindamycin and gentamicin when admixed together also remained within ten percent of the original concentration. Similar results were found with concentrations of clindamycin and amikacin when admixed together. Tobramycin and clindamycin formed a lasting precipitate upon initial contact when admixed under the study conditions.

Compatibility of clindamycin phosphate with aztreonam in polypropylene syringes and with cefoperazone sodium, cefonicid sodium, and cefuroxime sodium in partial-fill glass bottles.

The stability and compatibility of clindamycin phosphate admixed with four beta-lactams, an experimental monobactam (aztreonam), and three cephalosporins (cefoperazone sodium, cefonicid sodium, and cefuroxime sodium), were studied. Aztreonam alone and the combination of clindamycin phosphate-aztreonam were prepared in duplicate polypropylene syringes. Each cephalosporin antibiotic as well as the three clindamycin phosphate-cephalosporin combinations were admixed in duplicate 100 ml partial-fill glass bottles containing either dextrose 5% in water or NaCl 0.9%. All solutions were examined, antibiotic concentrations were determined, and pH was measured at the time of admixture and 1, 4, 8, 12, 24, and 48 hours later. The solutions were maintained at room temperature under fluorescent lighting for the length of the study. Antibiotic concentrations were determined by drug-specific high performance liquid chromatographic assays. Significant instability or incompatibility was defined as a decrease in concentration of greater than ten percent relative to the initial concentration measured at the time of admixture. All antibiotics were stable for 48 hours. In the combination studies, clindamycin was stable for 48 hours, both in partial-fill glass bottles and syringes. Aztreonam, cefoperazone, cefonicid, and cefuroxime were also stable for 48 hours.

Tolerance and Percutaneous Absorption of Topically Applied Arildone

Arildone, an investigational antiviral agent, was compared to both its vanishing cream and 90% dimethyl sulfoxide (DMSO) solution vehicles to determine cutaneous and systemic tolerance as well as percutaneous absorption. In separate studies, immunosuppressed patients randomly received either arildone in vanishing cream (study 1), arildone in DMSO solution (study 2), or the vehicles without arildone. Test formulations were applied to the same area of one forearm four times daily for seven days. Blood, urine, and fecal samples were collected on days 1, 4, and 7, and patients were observed daily. Arildone was sporadically detected in biologic specimens suggesting limited percutaneous absorption. Unexpectedly, DMSO did not appear to enhance absorption of the drug. No clinical or laboratory evidence of systemic intolerance was observed for any preparation. While cutaneous tolerance was excellent for the vanishing cream preparations, the DMSO preparations were associated with a high (90%) incidence of erythematous reactions.

Agreement between capillary and arterial serum gentamicin concentrations in neonates.

Due to inherent difficulties in blood sampling in neonates, specimens for laboratory analyses are often obtained by heel puncture technique. While agreement between venous or arterial and capillary concentrations of some substances has been reported, that for gentamicin, when obtained by heel stick, has not. Simultaneously obtained heel stick (capillary) and umbilical artery (arterial) serum samples were analyzed for gentamicin concentrations in 20 preterm neonates. Further, 14 subjects underwent manual manipulation of the heel to encourage blood flow before sampling to test the effect of such manipulation on gentamicin concentration. The agreement between capillary and arterial serum concentrations of gentamicin was found to be excellent in infants greater than 1000 g body weight. Manipulation of the heel had no effect on this agreement.