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Objectives: To evaluate whether antistaphylococcal prophylaxis in infants and young children with cystic fibrosis (CF) would suppress the acquisition of Staphylococcus aureus and delay the onset of the manifestations of bronchopulmonary disease., Study Design: A 7-year, multicenter, double-blind, placebo-controlled study of continuous antistaphylococcal therapy. Otherwise healthy children <2 years of age with CF were randomly assigned to be treated with daily cephalexin (80-100 mg/kg/day) or placebo. Clinical, microbiologic, laboratory, radiographic, and anthropometric outcomes were evaluated., Results: Of 209 children enrolled, 119 completed a 5- to 7-year course of therapy. Mean age at enrollment was 15.6 and 14.1 months in the cephalexin and placebo groups, respectively. Respiratory cultures from children treated with cephalexin were significantly less likely to be positive for S aureus (6.0% vs 30.4%; P <.001). They were, however, much more likely to be positive for Pseudomonas aeruginosa (25.6% vs 13.5%; P <.009). These differences became apparent in the first year after enrollment and persisted over the duration of the study. In contrast to these microbiologic differences, there were no differences in clinical outcome measures, including radiographic (Brasfield score, 23.4 vs 23.2) or anthropometric scores or pulmonary function., Conclusions: Although long-term prophylaxis with cephalexin successfully delayed the acquisition of S aureus, it enhanced colonization with P aeruginosa and did not lead to clinically significant improvement in major health outcomes. These data do not support routine antistaphylococcal prophylaxisin otherwise healthy infants and young children with CF.

To update the clinical profile of pediatric patients hospitalized with RSV infection, we retrospectively reviewed the records of 246 children (male:female ratio 1.44:1) admitted during one season to a tertiary-care hospital. The most common admitting diagnoses were bronchiolitis (37.4%), pneumonia (32.5%), and possible septicemia (13%). Median age was 3 months; median length of stay, three days. Twice as many minorities were admitted with RSV infection as all other admissions during the same year. Family history of asthma, while common (35%), did not affect length of stay or complications. Of the 38 (15%) patients requiring intensive care, 29 (76%) underwent ventilation. Patients with underlying cardiopulmonary disease had more complications, were more likely to require intensive care (about 50%), and had significantly longer hospital stays than others. All three patients (1.2%) who died had congenital heart disease. Common risk factors included young age, chronic cardiopulmonary disease, male sex, and possibly family history of asthma. Although the most typical clinical diagnoses remain bronchiolitis and pneumonia, a systemic illness resembling the sepsis syndrome has emerged at our institution as a significant clinical presentation.

To assess the effect of ribavirin on pulmonary function in infants with respiratory syncytial virus bronchiolitis, we performed a randomized (nonmatched), double blinded, placebo-controlled study of 19 infants with RSV bronchiolitis. Infants with underlying respiratory, cardiac or immunologic disease were excluded. Patients were given ribavirin (10) or placebo (9) via an aerosol generator for 18 hours/day for 3 days. Pulmonary function (dynamic compliance, total lung resistance) was calculated using a pneumotachographic method on Days 1, 2 and 7. Differences between groups on clinical criteria were not found. Approximately one-half of each group showed increased compliance and decreased lung resistance after 24 to 48 hours of therapy. By Day 7 compliance had increased 30% in the placebo group and 210% in the ribavirin-treated infants (P = 0.05). Significant differences in the rate of change of lung resistance were not seen by Day 7. We conclude that previously noted improvements in the early course of respiratory syncytial virus bronchiolitis treated with ribavirin do not appear to be a result of measurable changes in pulmonary function. However, paradoxical increases in airway resistance were not found in patients treated with ribavirin.

Objective: To measure first-dose and steady-state plasma, urine, and sputum concentrations of cefepime and make preliminary assessments of the clinical efficacy of cefepime in patients with cystic fibrosis., Design: Open noncomparative clinical trial., Setting: Memorial Miller Children's Hospital of Long Beach, Calif., Participants: Twelve patients, aged 4 to 41 years, with a confirmed diagnosis of cystic fibrosis and chronic bronchopulmonary infections., Interventions: Patients received cefepime at 50 mg/kg per dose (maximum dose, 2 g per dose) given intravenously every 8 hours. Clinical evaluations, pulmonary function tests, quantitative sputum cultures, and sensitivity testing were performed before, at the end of, and 2 weeks after therapy., Measurements and Main Results: Mean (+/- SD) peak plasma concentrations after the first dose were 148.2 (36.6) mg/L; the following other values were included: half-life, 1.59 (0.46) hours; area under the curve, 292 (94) microgram/h per milliliter; total-body clearance, 3.01 (1.46) mL/min per kilogram; volume of distribution at steady state, 0.32 (0.10) L/kg; and percent of dose recovered in urine, 52% (27%). Steady-state and first-dose values were similar. Trough levels varied from 6.4 to 7.2 mg/L. Mean (+/- SD) sputum concentrations at steady state varied from 6.3 (5.4) to 4.8 (2.3) mg/L. At completion of therapy, nine of 10 patients' conditions were improved as indicated by clinical scores (greater than 10 points), forced vital capacity (greater than 10%), and a greater than or equal to 1 log decrease in sputum bacterial concentration. Cefepime was well tolerated in 10 patients, but rash and light-headedness developed in two patients. Pseudomonas aeruginosa minimum inhibitory concentration90 increased from the start (64 mg/L) to the end of therapy (256 mg/L) and was unchanged 2 weeks later., Conclusion: Based on these data and the potential advantage of a single agent for the treatment of mixed infections (Staphylococcus aureus and P aeruginosa), comparative clinical trials of cefepime and standard therapy for bronchopulmonary exacerbations in patients with cystic fibrosis appear to be warranted.

Studies from Africa suggest that vitamin A supplementation may reduce morbidity and mortality rates associated with measles among poorly nourished children. We studied 20 children with measles in Long Beach, Calif., and found that 50% (95% confidence interval; 28% to 72%) were vitamin A deficient. This frequency among presumably well nourished American children supports evaluation of vitamin A status as a part of acute management of measles in the United States.

Measles has become epidemic over most of the world, with an important increase in the number of cases and associated morbidity and mortality in the United States since 1986. The two major factors responsible for this rise in the number of cases are, first, the increase in unvaccinated preschool-age children and, second, vaccine nonresponders (approximately 5%). The highest attack rate occurred in teenagers (15 to 19 years old) and in nine states (82% of cases). This situation has prompted revised immunization recommendations for those counties reporting more than five cases of measles among preschool-age children during each of the previous 5 years. In these counties, a first dose with monovalent measles vaccine is recommended at 9 months of age, followed by a second dose with measles, mumps, and rubella vaccine at 15 months of age, and revaccination of all children at the time of school entry. Recent publications regarding the use of vitamin A and certain antiviral agents are encouraging and are discussed in the manuscript. All cases of measles should be reported and investigated promptly. A good outbreak-control program will depend on the rapid recognition of the disease, a team approach, and prompt vaccination or IgG administration to susceptible persons.

This report emphasizes new clinical information about bacterial meningitis in infants and children. Important elements of diagnosis include examination for the presence of shock and increased intracranial pressure. In such cases, initial treatment should focus on appropriate fluid therapy, administration of oxygen, reduction of intracranial pressure and use of corticosteroids. Currently, antibiotics of choice include ampicillin plus either cefotaxime or ceftriaxone in young infants, and one of these cephalosporins in older patients (beyond 3 months of age). Shorter durations of therapy (5 to 7 days for meningococcus, 7 days for haemophilus and 7-10 days for pneumococcus) are now commonly employed. In many centers, dexamethasone is started before the first dose of antibiotic and continued for 4 days to reduce neurologic and audiologic sequelae. Future trends will include studies of endotoxin neutralizers and non-steroidal anti-inflammatory drugs to reduce further tissue injury in meningitis. Prevention of meningitis is the ultimate goal. Since Haemophilus influenzae vaccination can now begin at 2 months, this approach may bring important results soon.

We compared the in-vitro activities of cefprozil, a novel oral cephalosporin, and of loracarbef, a new oral carbacephem, with other agents against middle ear fluid isolates obtained from children with acute otitis media. These included Streptococcus pneumoniae, Haemophilus influenzae and Branhamella catarrhalis. Cefprozil activity (MIC50 and MIC90) against S. pneumoniae was 0.25 and 0.50 mg/l; against H. influenzae 8 and 16 mg/l; against B. catarrhalis 2 and 2 mg/l. Loracarbef activity (MIC50 and MIC90) against S. pneumoniae was 1 and 2 mg/l; against H. influenzae 8 and 16 mg/l; against B. catarrhalis 1 and 8 mg/l. Cefprozil was four-fold more active against S. pneumoniae than loracarbef but similar to amoxycillin, amoxycillin/clavulanate, cefaclor, cefixime, cefuroxime and trimethoprim/sulfamethoxazole (TMP/SMX). Against H. influenzae, cefprozil was similar to loracarbef and other agents through less active than TMP/SMX and cefixime. Against B. catarrhalis, cefprozil was four-fold more active than loracarbef, cefaclor and cefixime but similar to the comparative antibiotics. Cefprozil and loracarbef activities were unaffected at pH 6 and 8 or in the presence of human serum, but there was a major diminution of activity for both agents at pH 5 and at inoculum sizes greater than or equal to 10(7) cfu/ml. Cefoprozil and loracarbef have consistent activity against middle ear pathogens and further pharmacokinetic and clinical studies appear warranted.

By using broth microdilution methods, the in vitro activity of tosufloxacin (A-64730), a new quinolone, was compared with those of other agents, including five quinolones, against geographically diverse cystic fibrosis sputum isolates obtained from 26 cystic fibrosis centers in the United States. These included Pseudomonas aeruginosa, conventional as well as especially resistant (ceftazidime, aztreonam, gentamicin, and/or tobramycin) isolates: Escherichia coli; Pseudomonas cepacia; Staphylococcus aureus; and Haemophilus influenzae. Tosufloxacin MICs for 50 and 90% of isolates of standard P. aeruginosa were 0.5 and 2.0 mg/liter, for resistant P. aeruginosa they were 4.0 and greater than 16.0 mg/liter, for E. coli they were less than or equal to 0.016 mg/liter, for P. cepacia they were 4.0 and 8.0 mg/liter, for S. aureus they were 0.063 and 0.063 mg/liter, and for H. influenzae they were less than or equal to 0.016 and 0.032 mg/liter, respectively. Tosufloxacin activities against standard and resistant strains of P. aeruginosa were similar to those of comparative quinolones. Against E. coli, tosufloxacin activity was similar to those of other quinolones. Against S. aureus, tosufloxacin activity was similar to those of trimethoprim-sulfamethoxazole and cephalexin, but tosufloxacin was more active than other agents. Against H. influenzae, tosufloxacin activity was similar to those of other quinolones. There was minor diminution of activity at pH 8.2 but major diminution of activity at pH 5.2 and at inoculum sizes of greater than or equal to 10(7) CFU/ml. Activity was unaffected by sputum but was enhanced by serum and by the omission of cation supplementation. Tosufloxacin has consistent activity against common cystic fibrosis pathogens. Its high degree of activity against S. aureus with activity maintained against P. aeruginosa and other gram-negative bacteria of interest suggests that further in vitro studies and assessment of activity in in vivo models of cystic fibrosis pulmonary infections are warranted.

We evaluated fleroxacin, a newer fluoroquinolone, against isolates from sputum from patients with cystic fibrosis. These isolates included rough and mucoid Pseudomonas aeruginosa, Pseudomonas cepacia, Staphylococcus aureus, Haemophilus influenzae, and Escherichia coli. Selected isolates were tested by the broth microdilution method to examine the influence of various pHs, inoculum sizes, and biological fluids (serum or sputum from patients with cystic fibrosis). Fleroxacin MICs for 50 and 90% of isolates of P. aeruginosa were 2.0 and 4 micrograms/ml, those for P. cepacia were 2 and 16 micrograms/ml, those for S. aureus were 0.5 and 1 microgram/ml, those for H. influenzae were 0.06 and 0.06 micrograms/ml, and those for E. coli were 0.01 and 0.03 micrograms/ml, respectively. Fleroxacin activity against mucoid P. aeruginosa was similar to the activities of enoxacin and ofloxacin but eightfold lower than that of ciprofloxacin. It was twofold more active than norfloxacin and enoxacin but was twofold less active than ciprofloxacin, ofloxacin, and nafcillin against S. aureus. Fleroxacin inhibitory activity against P. cepacia was two- to fourfold lower than that of ciprofloxacin but eightfold greater than those of the other quinolones tested. Alterations in pH, diluent, and inoculum size did not significantly affect fleroxacin activity. These results, combined with available pharmacokinetic and tissue distribution data, support the need for clinical evaluation of fleroxacin in pulmonary infections in patients with cystic fibrosis.

On the basis of preliminary in vitro data, we evaluated E-1040, a new cephalosporin, against 188 cystic fibrosis (CF) sputum isolates obtained from 26 CF centers in the United States. These isolates included mucoid and nonmucoid Pseudomonas aeruginosa, Pseudomonas cepacia, Staphylococcus aureus, Haemophilus influenzae, and Escherichia coli. In addition to MICs measured under standard conditions, selected isolates were tested at various pH values, inoculum sizes, and diluent (CF serum and sputum) conditions. E-1040 activities (MICs for 50 and 90% of the strains) against the isolates were as follows: P. aeruginosa (mucoid and nonmucoid), 1 and 4 micrograms/ml; P. cepacia, 4 and 16 micrograms/ml; S. aureus, 8 and 8 micrograms/ml; H. influenzae, 1 and 4 micrograms/ml; and E. coli, less than or equal to 0.12 and less than or equal to 0.12 microgram/ml. E-1040 activity against mucoid P. aeruginosa was 4-fold greater than that of aztreonam, 16-fold greater than that of ceftazidime, and 32-fold greater than that of piperacillin. E-1040 was similar to other broad-spectrum cephalosporins against S. aureus, H. influenzae, and E. coli. Bactericidal activity was less than or equal to 1 dilution of MIC for 88% of the strains, although kinetic studies with mucoid strains of P. aeruginosa demonstrated effective killing only at eight times the MIC. Variations in pH from 5 to 8, in inoculum size from 10(3) to 10(7) CFU/ml, and in diluent (CF serum or CF sputum) did not affect E-1040 activity.

Invasive Haemophilus influenzae type b infections are a major cause of severe infections in children between 2 months and 5 years of age. Meningitis, arthritis, pneumonia, cellulitis, osteomyelitis, and epiglottitis affect approximately 25,000 patients annually and are a major cause of mortality and morbidity in children. H. influenzae type b clinical syndromes, diagnostic methods, epidemiology, immunity, and treatment are discussed in this review. Although potent antibiotics have long been available for treatment, mortality and morbidity rates have not declined substantially in the last 15 years. Prevention of disease is therefore a continuous medical challenge. Secondary cases can be prevented by identification of the high-risk groups and the application of appropriate techniques, including antimicrobial prophylaxis. Primary prevention is the major goal of current research. H. influenzae type b vaccines currently are available for protection of infants 18 months of age and older. Prevention of primary and secondary disease and future developments, including new vaccine strategies, are stressed.

Staphylococcus aureus is usually the first bacterial pathogen detected in the respiratory secretions of patients with cystic fibrosis. This review briefly examines the characteristics of this host-parasite relationship in terms of current knowledge about the toxicity of the organism, mechanisms of respiratory tract injury, therapy and prevention. Recent evidence indicates that viral infection plays a role in the initial damage of the respiratory epithelial cells and staphylococcal colonization ensues. Affinity of staphylococcus for cystic fibrosis mucus, mucociliary abnormalities and unknown factors contribute to persistent colonization with this organism causing progressive pulmonary damage and possibly influencing Pseudomonas infection. Most of the evidence today indicates that aggressive antibiotic management directed against S. aureus is warranted in all stages of bronchopulmonary infection in cystic fibrosis. Future efforts to prevent colonization and the toxic and immunopathic consequences of staphylococcal infection are also important. One study is in progress that examines antibiotic prevention in the early stages of cystic fibrosis. Future investigations need to address other strategies including vaccines, antitoxins, anti-inflammatory agents, immunomodulators, and antibiotic regimens.

To test the hypothesis that abnormalities on 67Ga-citrate scans parallel the clinical course of acute osteomyelitis and revert to normal with successful antibiotic therapy, serial scans were performed in ten children. Scans improved markedly within the first two to four weeks of treatment, but abnormalities persisted at six or more weeks in over 50% of the cases, despite complete clinical resolutions of disease.

Four diluents were compared as reference standards for the assay of gentamicin in cerebrospinal fluid (CSF): human CSF, human serum, distilled water, and 150 mmol NaCl/4.5 mmol CaCl2. Standards prepared in pooled human serum were the best alternative to CSF for the assay of gentamicin and were also useful for the assay of tobramycin, netilmicin, amikacin, and sisomicin. The pH (6.0-9.8) of CSF did not alter the results of the assay.

Twenty-one cystic fibrosis patients under 3 years of age were enrolled in an open multicenter study to assess the feasibility of the study design and to compare selected pharmacologic features of cephalexin or dicloxacillin administered orally for 2 months. Patient tolerance and compliance were significantly less for dicloxacillin (p less than .01 and p less than .001, respectively). Superficial Candida infections were more common in the cephalexin group (p = 0.02), however increased stool frequency and nonspecific diaper rashes were more prevalent in patients receiving dicloxacillin (p less than .05). Staphylococcus aureus was isolated from respiratory secretions after 2 months from two dicloxacillin and no cephalexin patients. Areas under the curve and peak serum concentrations were higher for cephalexin (p less than .05 and p = .02), but antistaphylococcal activity in serum was higher for dicloxacillin (p less than .05) due to a lower mean MIC compared to cephalexin. Deep pharyngeal plus routine throat culture yielded more pathogens than either method alone. Express mail and central processing of respiratory specimens was efficient for most organisms, however there was some loss of Streptococcus pneumoniae and Haemophilus influenzae. Cephalexin was associated with better patient acceptance and compliance despite higher rates of superficial fungal infections as compared to dicloxacillin. Cephalexin, routine bacteriologic throat swabs processed locally or centrally, mail-in urine compliance assessment and a multicenter design are feasible components for a long-term prospective evaluation of antibiotic prophylaxis in patients with cystic fibrosis.

Twenty-six children, aged 2 months to 15 years, were treated with intravenous ceftriaxone sodium, 37.5 mg/kg every 12 hours, for an average of seven days. Clinical and microbiologic cures occurred in 19 of 21 patients, from whom bacterial pathogens were cultured. Ceftriaxone was not effective in treating an 18-month-old infant with periorbital cellulitis caused by relatively resistant Staphylococcus aureus. A relapse occurred in a 2-month-old infant with meningitis caused by ceftriaxone-sensitive Salmonella. Eleven patients had transient diarrhea, superficial candidiasis developed in ten patients, and one patient experienced skin flushing during administration of the antibiotic. Transient asymptomatic laboratory abnormalities were detected in 15 patients; nine patients had elevated serum concentrations of transaminases or bilirubin, 11 had thrombocytosis, three experienced eosinophilia, and one had thrombocytopenia. Transient suppression of normal flora of the intestine occurred in 21 patients. Side effects were not serious enough to warrant discontinuing ceftriaxone therapy in any patient.

In a multicenter randomized trial, 107 children with bacterial meningitis were initially given either cefuroxime or ampicillin plus chloramphenicol. Patients were alternately assigned to 7- or 10-day courses of the designated antimicrobial regimen. CSF isolates included Haemophilus influenzae type b (89, of which 25% were beta-lactamase positive), Streptococcus pneumoniae, and Neisseria meningitidis. Although mean CSF bactericidal titers against Haemophilus isolates were 1:6 in each treatment group, H. influenzae was cultured from CSF in four of 39 patients receiving cefuroxime, 24 to 48 hours after initiation of therapy, compared with none of 40 patients given ampicillin plus chloramphenicol (P = 0.11). Clinical cure rates were similar (95%); one death occurred in each group. One child given cefuroxime had persistent meningitis after 5 days of therapy, and mastoiditis with secondary bacteremia developed in one on day 10. Three patients had relapse or reinfection. One patient who received cefuroxime for 10 days had a relapse of epiglottitis 17 days later, and of the patients given ampicillin plus chloramphenicol, one had a relapse of meningitis 1 week after 7 days of therapy, and bacteremia developed in one 42 days after completion of 10 days of therapy. No increase in either in-hospital complications or relapses occurred with a 7-day treatment course. Proof of the equivalence of the antibiotic regimens and the efficacy of 7-day courses of treatment, as well as the consequences of delayed CSF sterilization, will require additional investigation.

The antibacterial activity of BMY-28142, a new aminothiazole cephalosporin, was measured by standardized broth microdilution and agar dilution methods against 450 gram-positive and gram-negative bacteria isolated from pediatric infections, including acute pulmonary exacerbations of cystic fibrosis. BMY-28142 activity was compared with that of aminoglycosides, beta-lactams, chloramphenicol, trimethoprim-sulfamethoxazole, vancomycin, and clindamycin. The activity of BMY-28142 in combination with other antimicrobial agents against Pseudomonas aeruginosa was also determined. Furthermore, the effects of inoculum and pH on BMY-28142 activity were evaluated. BMY-21842 was active against most of the gram-positive and gram-negative isolates, with the exception of methicillin-resistant Staphylococcus aureus and Pseudomonas cepacia. The combination of BMY-28142 with tobramycin was often synergistic, and combinations of BMY-28142 with either polymyxin B or imipenem were usually antagonistic. BMY-28142 antibacterial activity could be adversely affected at extremes of medium pH and by high inoculum densities.

Chloramphenicol was introduced into medical practice in 1949. At therapeutic concentrations of 10 to 20 micrograms drug per ml, the drug inhibits bacterial ribosomal and, to a lesser extent, mammalian mitochondrial protein synthesis but concentrations above 60 micrograms drug per ml induce progressive reduction of oxygen-dependent cellular metabolism. Some adverse reactions (e.g. bone marrow suppression and the "gray baby syndrome") reflect these effects. The pathogenesis of chloramphenicol-induced aplastic anemia remains unclear. Chloramphenicol is most bioavailable after oral administration and has a remarkable ability to diffuse into body fluids and tissues. However, there are wide interindividual variations in its metabolism and elimination, particularly in newborns. Chloramphenicol is indicated for invasive ampicillin-resistant H. influenzae infections; for patients allergic to penicillin with pneumococcal, meningococcal or H. influenzae meningitis; in patients under 8 years of age with Rocky Mountain spotted fever; and for the treatment of brain abscess and other severe anaerobic infections (excluding endocarditis) due to B. fragilis. Other indications include selected patients with Salmonella meningitis or carditis, rickettsioses and intraocular infections. Unravelling the pathogenesis of chloramphenicol-induced aplastic anemia is critical to more widespread application of this remarkable antimicrobial.

Sisomicin, at 4.5 mg/kg per day, was prescribed for the therapy of serious bacterial infections of hospitalized infants, children, and adolescents. Eleven children received full treatment courses, with 10 clinical and 9 bacteriological cures. Three patients with underlying disease (two cystic fibrosis and one aplastic anemia) accounted for the failures. Mean half-life was 98.3 min (range, 26.1 to 159.3), and peak serum concentrations 10 min after intravenous infusion were similar (5 to 6 mug/ml) on days 1, 3, and 5 of therapy. Mean urinary concentrations were 54.3 mug/ml; 31 to 47% of the drug was excreted within the 8-h dosage interval. The drug was tolerated well by all patients; however, one patient, receiving the longest duration of therapy (26 days), developed reversible nephrotoxicity.

Stool specimens from children with gastroenteritis and their household contacts were cultured for Yersinia enterocolitica by direct plating onto routine laboratory media. These stools were also inoculated into phosphate-buffered saline and subcultured to the same media after 1 day or 3 weeks of incubation at 4 degrees C. Y. enterocolitica was isolated from 174 index cases and 34 household contacts. One hundred eighty-one isolates were of serotype O:3, and the remaining 21 belonged to other serotypes. Eighty-one percent (147/181) of O:3 isolates were recovered by direct plating, and 6.1% (11/181) and 13% (23/181) were recovered by 1-day and 3-week cold enrichment, respectively. For other serotypes, 26% (7/27), 0%, and 74% (20/27) were isolated by direct plating, 1-day cold enrichment, and 3-week cold enrichment, respectively. The efficacy of the cold enrichment for the patients were still symptomatic, 94 and 6% of Y. enterocolitica were identified by direct plating and cold enrichment, respectively. Isolation rates were 66% by direct plating and 34% by cold enrichment when stools were obtained from asymptomatic carriers or from those convalescing from Y. enterocolitica gastroenteritis. These results indicate that the cold enrichment methods increase the sensitivity of Y. entercolitica culture methods considerably in convalescent and asymptomatic subjects but only minimally in patients with diarrhea caused by serotype O:3.

The tendency for bacteria to develop resistance to enoxacin (Cl-919, AT-2266), a new oxyquinolone derivative, was investigated in vitro and in vivo. The mutation frequencies of Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Salmonella sp., and Haemophilus influenzae to enoxacin, norfloxacin, nalidixic acid, tobramycin, cephalexin, cefotaxime, ampicillin, azlocillin, oxacillin, and ticarcillin were determined by plating large numbers of organisms onto antibiotic-containing agar. Enoxacin resistance developed infrequently. For example, the mutation frequency of Ps. aeruginosa in the presence of enoxacin was 1 in 2.8 X 10(9) cells as compared to 1 in 1.1 X 10(6) for nalidixic acid. The increase in MIC after serial transfer through increasing concentrations of enoxacin ranged from 8-fold for Ps. aeruginosa and Staph. aureus to 256-fold for H. influenzae. Rats with chronic Ps. aeruginosa pneumonia were given subtherapeutic doses of enoxacin daily for ten weeks. Two rats were sacrificed weekly and the homogenized lungs were cultured on agar containing 5 mg/l of enoxacin and on antibiotic-free agar. No organisms resistant to 5 mg/l of enoxacin were recovered. No increase in the minimum inhibitory concentration of enoxacin for the infecting organism was seen.

Lack of correlation between quantitative minimal inhibitory concentration (MIC) determinations and disk diffusion susceptibility tests in our laboratory prompted a study to reevaluate the use of the disk diffusion test for sulfonamide susceptibility testing of Neisseria meningitidis. One hundred and sixty-three recent clinical isolates of N. meningitidis were examined for sulfonamide susceptibility by the agar dilution and disk diffusion methods. Optimal inocula for each of the tests were determined, and thereafter all disk diffusion tests were compared with quantitative MICs as determined by the agar dilution method using sulfadiazine and an inoculum of 10(6) colony-forming units (CFU)/ml. The clearest and most reproducible zone diameters were obtained with a 10(7)-CFU/ml inoculum in the disk diffusion test. There was complete correlation between the disk zone diameters for 300-mug disks of sulfadiazine and sulfathiazole and the agar dilution test MICs. All isolates with a zone diameter of <20 mm were resistant to sulfadiazine, whereas those with zone diameters of >/=30 mm were susceptible. False susceptible and false resistant readings were obtained with 300-mug sulfisoxazole disks. These data suggest that inocula and type of sulfonamide are critical factors in the disk diffusion test for meningococcal susceptibility testing. Sulfonamide disks are not interchangeable for susceptibility testing of meningococci.

Concentrations of latamoxef, cefoperazone and piperacillin, administered intravenously, were measured in serum and sputum of cystic fibrosis patients with recurrent pulmonary infections, chronically colonized with Pseudomonas aeruginosa. Serum pharmacokinetic data were consistent with prior reports. Peak sputum to peak serum concentrations were approximately 3% for each antimicrobial. However, the more prolonged sputum concentrations of piperacillin were reflected in greater areas under the sputum concentration-time curve and a longer duration above the MIC50 of tested P. aeruginosa strains for that drug.

277 5-7-day-old white Swiss mice were infected intranasally with Herpes simplex virus type 2 (HSV2) to mimic disseminated herpetic infection in human newborns. The antiviral efficacy of acyclovir, vidarabine and specific antiserum (SAS) alone and in combination was assessed. A significant increase in survival rate (52%) was observed with the combination of acyclovir (80 mg/kg/day) and vidarabine (125 mg/kg/day) compared to either compound (24 and 6%, respectively) when therapy was begun 30 h after infection and continued daily for the next 4 days. Combinations of acyclovir, vidarabine and SAS had less protective effect (8%) than acyclovir with SAS (32%) or vidarabine with SAS (12%). No improvement was observed in survival rate of HSV2-infected mice treated with SAS as compared with controls (0% and 5%, respectively). These results suggest the enhanced antiherpes effect in newborn mice is due to synergism of acyclovir and vidarabine, a combination deserving further evaluation for the treatment of HSV2 infections in humans.