Helen Kusmiesz

Five vs. ten days of therapy for acute otitis media

In a double blind study 175 patients with acute otitis media were randomized into 2 treatment groups: 10 days of therapy with cefaclor or 5 days of therapy followed by 5 days of placebo. The dosage of cefaclor was 40 mg/kg/day administered orally in equally divided doses at 12-hour intervals. Tympanocentesis before treatment yielded specimens that contained Streptococcus pneumoniae or Haemophilus influenzae or both in 55% of specimens. Branhamella catarrhalis was isolated from 21% of specimens.

Benefits and risks of sequential parenteral--oral cephalosporin therapy for suppurative bone and joint infections.

Seventy-five infants and children with suppurative skeletal infections were managed with a sequential parenteral–oral regimen of cephalosporin antibiotic therapy. Initially, parenteral antibiotics (cefamandole for 48 patients and cefuroxime for 27 patients) were given for a median of 5 days. Oral therapy was with large doses of cefaclor (150 mg/kg/day) or cephalexin (100 mg/kg/day). Eight patients (11%) had inadequate serum bactericidal activity with cefaclor. Six of them were successfully managed with alternative oral antibiotics, and parenteral therapy resumed in one patient. Chronic disease developed in a child who was continued on oral cloxacillin therapy in spite of absent serum bactericidal activity. It is concluded that oral therapy can be successful for the majority of patients but that it is hazardous and not indicated if careful laboratory monitoring of compliance and serum bactericidal activity cannot be performed.

Trimethoprim-sulfamethoxazole therapy for shigellosis.

Twenty-eight infants and children hospitalized for severe shigellosis were treated orally either with ampicillin trihydrate (100 mg/kg/day administered in divided doses every six hours) or with trimethoprim-sulfamethoxazole (trimethoprim, 10 mg; sulfamethoxazole, 50 mg/kg/day in divided doses every 12 hours) for five days. Four patients with ampicillin-resistant shigellae continued to have diarrhea and positive stool cultures during therapy. Patients with susceptible shigellae treated with ampicillin and all patients treated with trimethoprim-sulfamethoxazole responsed promptly and comparably within an average of 1.6 and 1.7 days, respectively, until stool cultures were negative, and 3.1 and 2.9 days, respectively, until diarrhea stopped. Patients with ampicillin-resistant shigellae responded to treatment with trimethoprim-sulfamethoxazole. It is concluded that trimethoprim-sulfamethoxazole is the best currently available drug for treatment of shigellosis in areas where multiple antibiotic resistance of shigellae is common.

Comparative efficacy of nalidixic acid and ampicillin for severe shigellosis

Nalidixic acid is effective in vitro against shigellae including strains multiply-resistant to antibiotics. A comparative study of acute shigellosis in infants and children involved 19 patients treated with ampicillin and 17 treated with nalidixic acid. Stool cultures remained positive longer with nalidixic acid treatment than with ampicillin therapy, and clinical response was slower. The rate of response to therapy was correlated with the serum levels of ampicillin. Though nalidixic acid eliminates shigellae from stools more rapidly than with symptomatic therapy alone, it cannot be recommended for routine treatment of acute shigellosis since it has little effect on the natural course of the illness. In special circumstances when dealing with shigellae that are resistant to ampicillin, tetracycline, and chloramphenicol, nalidixic acid may have a limited use.

Absorption of ampicillin and nalidixic acid by infants and children with acute shigellosis.

Thirty‐seven infants and children with acute shigellosis were treated with orally administered ampicillin or nalidixic acid. Peak plasma levels and dose‐response curves suggested two patient populations. Five of 16 patients receiving nalidixic acid had a pronounced delay in absorption, while the others had the anticipated peak levels and plasma half‐lifes. All patients had a lower percentage of conjugated drug and of drug present as the hydroxynalidixic acid metabolite on the first day of treatment than during convalescence. Thus, some patients with diarrhea had altered absorption and all had altered metabolism of nalidixic acid during the acute phase of shigellosis. In 10 of 21 ampicillin‐treated patients there were depressed plasma levels and prolonged half‐lifes. These were statistically likely to be younger, to have more severe diarrhea, and to have lower body weight than those with normal peak plasma levels and plasma clearance rates.

Comparison of trimethoprim-sulfamethoxazole and ampicillin therapy for shigellosis in ambulatory patients**

One hundred seventy-four infants and children with acute diarrhea were treated as ambulatory patients with either ampicillin (100 mg/kg/day orally in four divided doses) or trimethoprim sulfamethoxazole (10 mg TMP and 50 mg SMX/kg/day orally in two divided doses). There were 65 patients with shigellosis. Responses of those treated with TMP/SMX and of those with susceptible Shigella treated with ampicillin were comparable. Patients with resistant organisms failed to respond to ampicillin. All Shigella , including ampicillin-resistant strains, were susceptible in vitro to TMP/SMX, and patients with ampicillin-resistant strains responded favorably to treatment with TMP/SMX. TMP/SMX appears to be the best, currently available drug for the treatment of shigellosis.

Comparison of orally absorbable and nonabsorbable antibiotics in shigellosis. A double-blind study with ampi-cillin and neomycin.

The effects of orally administered neomycin and ampicillin on bacteriological cure and clinical course in acute shigellosis were assessed by a double-blind treatment study of 30 hospitalized infants and children. “Bacteeriological failure” (cultures positive more than 48 hours after initiation of therapy) occurred in 87 per cent of patients who received neomycin and in 13 per cent of those treated with ampicillin. All Shigellae showed in vitro susceptibility to the antibiotics used. “Clinical failure” (persistence of diarrhea beyond 5 days after starting therapy or removal of the patients from study or both) occurred in 60 per cent of the neomycin-treated group and in 13 per cent of those treated with ampicillin. Statistically significant differences between neomycin and ampicillin therapy were also demonstrated for the following parameteers: days until stool culture was negative, presence of Candida species in the stool, and days until afebrile. The failure of oral neomycin therapy in shigellosis supports the concept that nonabsorbable antimicrobial agents are not optimal therapy for acute shigellosis regardless of in vitro susceptibility.

Pharmacokinetics of erythromycin ethylsuccinate and estolate in infants under 4 months of age.

We studied the pharmacokinetics of erythromycin estolate and ethylsuccinate suspensions in infants under 4 months of age who were being treated for chlamydial infections or pertussis. We conducted our studies after the initial dose of 10 mg/kg and subsequently during steady-state treatment. The estolate preparation resulted in higher peak concentrations in sera, and its absorption and elimination half-lives were longer. Peak concentrations occurred 3 h after a dose with the estolate preparation and 1 h after a dose with the ethylsuccinate preparation. The area under the curve for the estolate preparation was about three times greater than that for the ethylsuccinate preparation. Based on these findings, we recommend that erythromycin estolate suspensions be given to young infants at 8- or 12-h intervals (30 mg/kg per day in three divided doses or 20 mg/kg per day in two divided doses) and that erythromycin ethylsuccinate is best given at 6-h intervals (40 mg/kg per day in four divided doses).

Role of genital mycoplasmas in young infants with suspected sepsis

To establish the prevalence of Mycoplasma hominis and Ureaplasma urealyticum in infants up to 3 months of age with suspected sepsis, blood, cerebrospinal fluid, and urine specimens from 203 patients with clinical signs and symptoms of sepsis were cultured for Mycoplasma in addition to routine bacterial cultures. Proved bacterial infections were identified in 24 patients, four of whom had bacteremia. M. hominis and U. urealyticum were not isolated from any of the 191 blood and 199 CSF specimens tested. Of 170 specimens of urine cultured for Mycoplasma, M. hominis was isolated in six patients, U. urealyticum in nine patients, and both organisms in one patient. Twelve of the positive cultures were voided urine specimens, and four were suprapubic bladder aspiration specimens. Genital mycoplasmas appear to be uncommon causes of sepsis or meningitis in young infants. Further studies are required to assess their role in abnormal conditions of the urinary tract in childhood.

Pharmacologic interactions among chloramphenicol, phenytoin and phenobarbital.

Bioactive chloramphenicol was measured in the sera of 34 infants and children receiving intravenous chloramphenicol succinate (25 mg/ kg/dose) as therapy for meningitis, pneumonia, brain abscess or Rocky Mountain spotted fever. In 17 children receiving chloramphenicol succinate alone, mean peak and trough serum concentrations of chloramphenicol were 25.3 and 13.4 μg/ml, respectively. Concurrent administration of chloramphenicol succinate and phenobarbital in six patients resulted in reduced peak and trough concentrations of chloramphenicol of 16.6 and 7.5 μg/ml, respectively (P < 0.05). Concurrent administration of chloramphenicol succinate and phenytoin in six patients resulted in an elevated mean peak serum concentration of chloramphenicol of 41.7 μg/ml (P < 0.05). Five other patients treated with phenytoin had indeterminate serum chloramphenicol half-lives with chloramphenicol concentrations of 29 to 90 μg/ml. Potentially toxic chloramphenicol concentrations occurred in 9 of 17 controls, 0 of 6 patients who had received phenobarbital (P = 0.001) and 11 of 11 patients who had received phenytoin (P = 0.008). Patients receiving combined chloramphenicol succinate and anticon-vulsant therapy require monitoring of serum concentrations of drug and adjustments in the dose of chloramphenicol succinate administered.