BACKGROUND: The efficacy and safety of piperacillin/tazobactam plus ceftazidime (PIPC/TAZ+CAZ) versus sulbactam/ampicillin plus aztreonam (SBT/ABPC+AZT) as empirical therapy for febrile neutropenia were assessed in children with hematologic disease and solid tumor. PROCEDURE: A prospective randomized study was performed to evaluate the clinical response of 70 febrile episodes in the PIPC/TAZ+CAZ arm and 64 evaluable febrile episodes in the SBT/ABPC+AZT arm of the study. Clinical efficacy was evaluated at 120 hours, with treatment outcome criteria defined as follows. Success was defined as disappearance of fever, clinical improvement, eradication of the infecting organism, and maintenance of a response for at least 7 days after discontinuation of treatment. RESULTS: An infection was documented microbiologically in 14 episodes (20%) in the PIPC/TAZ+CAZ arm and in 8 episodes (13%) in the SBT/ABPC+AZT arm. The success rate was 57.1% in the PIPC/TAZ+CAZ arm and 62.5% in the SBT/ABPC+AZT arm (P>0.05). No major adverse effects were observed in the study. CONCLUSIONS: PIPC/TAZ+CAZ and SBT/ABPC+AZT are effective and safe for initial empirical treatment of febrile episodes in neutropenic pediatric patients. The clinical efficacy of SBT/ABPC+AZT is equivalent or superior to that of PIPC/TAZ+CAZ, the effect of which is already proven against febrile neutropenia. Therefore, SBT/ABPC+AZT may be a treatment of choice for febrile neutropenia in pediatric cancer patients.

Most cases of neonatal group B streptococcal disease with early onset have an intrapartum pathogenesis. Attack rates are increased substantially in infants born to mothers with prenatal group B streptococcal colonization and various perinatal risk factors (premature labor, prolonged membrane rupture, or intrapartum fever). In a randomized controlled trial, we studied the effect of selective intrapartum prophylaxis with ampicillin in 160 such high-risk women. In infants born to mothers who received intravenous ampicillin during labor, as compared with controls who received no treatment, neonatal colonization with group B streptococci was present in 8 of 85 (9 percent) versus 40 of 79 (51 percent; P less than 0.001), colonization at multiple (greater than or equal to 3) sites was observed in 3 of 85 (4 percent) versus 24 of 79 (30 percent; P less than 0.001), and bacteremia occurred in none of 85 versus 5 of 79 (6 percent; P = 0.024). The side effects of ampicillin were limited to a single episode of urticaria in a mother who had no history of penicillin allergy. We conclude that intrapartum ampicillin prophylaxis in women with positive prenatal cultures for group B streptococci who have certain perinatal risk factors can prevent early-onset neonatal group B streptococcal disease.

The duration of infection and the quantity of Ag presented in vivo are commonly assumed to influence, if not determine, the magnitude of T cell responses. Although the cessation of in vivo T cell expansion coincides with bacterial clearance in mice infected with Listeria monocytogenes, closer analysis suggests that control of T cell expansion and contraction is more complex. In this report, we show that the magnitude and kinetics of Ag-specific T cell responses are determined during the first day of bacterial infection. Expansion of Ag-specific T lymphocyte populations and generation of T cell memory are independent of the duration and severity of in vivo bacterial infection. Our studies indicate that the Ag-specific T cell response to L. monocytogenes is programmed before the peak of the innate inflammatory response and in vivo bacterial replication.

To assess the cause of nonspecific vaginitis, we performed a prospective case-control study of vaginal flora and a randomized unblinded trial of different therapies. Haemophilus vaginalis was isolated from 17 to 18 women with signs of vaginitis but only one of 18 normal matched controls (P less than 0.002). The concentration of anaerobic bacteria in vaginal washings also was increased in patients. Clinical improvement and eradication of H. vaginalis occurred in one of seven patients given sulfonamide vaginal cream, two of 15 given oral doxycycline, nine of 27 given oral ampicillin, and 80 of 81 given oral metronidazole. On the seventh day of therapy signs of nonspecific vaginitis persisted in 31 of 31 with, and in two of 92 without, persistent H. vaginalis infection (P less than 0.001). These data suggest the causal role of H. vaginalis in nonspecific vaginitis, possibly in concert with vaginal anaerobes. The widespread use of sulfonamide creams is inappropriate. Metronidazole is effective, but its efficacy must be weighed against its possible toxicity.

In randomized, double-blind trials of antibiotic therapy for acute otitis media that determined both clinical and bacteriologic outcomes, clinical success rates were (93%) 236 of 253 for patients with bacteriologic success,(62%) 25 of 40 for those with bacteriologic failure, and (80%) 124 of 155 for those with nonbacterial acute otitis media. These rates were used to calculate the effectiveness of three strategies for assessing drug efficacy:(1) tympanocentesis and culture before and during therapy (bacteriologic efficacy),(2) tympanocentesis before therapy and assessment of clinical efficacy in bacterial acute otitis media, and (3) no tympanocentesis and assessment of clinical efficacy in clinical (total) acute otitis media. For a drug with a bacteriologic efficacy of 100%, calculated clinical efficacy was 93% for bacterial acute otitis media and 89% for clinical acute otitis media. For a drug with bacteriologic efficacy of 27%, a rate consistent with no antibacterial therapy, efficacy was 71% for bacterial acute otitis media and 74% for clinical acute otitis media. We conclude that if efficacy is measured by symptomatic response, drugs with excellent antibacterial activity will appear less efficacious than they really are and drugs with poor antibacterial activity will appear more efficacious than they really are. The predominant phenomenon is that drugs with poor antibacterial activity will appear to be clinically effective in the treatment of acute otitis media.

Eighteen institutions collaborated in evaluating the comparative efficacy of combined ampicillin and gentamicin therapy with and without intrathecal administration of gentamicin on the clinical and bacteriologic responses of 117 infants with meningitis caused by gram-negative enteric bacteria. There was a random distribution of patients within the two study groups with regard to age on enrollment, birth weight, sex, race, number of infants greater than 30 days of age, the etiologic agent, and their antimicrobial susceptibilities. There were no statistically significant differences (P greater than 0.05) in mortality, morbidity, or days that cerebrospinal fluid cultures remained positive among the infants in the two treatment groups. The case fatality rate for all patients was 32%; that for full-term infants (18%) was significantly lower (P less than 0.01) than that for low-birth-weight infants (45%) or for the patients greater than 30 days of age (48%). Fifty-one of the 80 (64%) survivors were assessed as normal on follow-up examinations performed up to four years after illness.

To monitor temporal trends and regional differences in antibiotic susceptibility, we measured the minimum inhibitory concentrations for penicillin G, ampicillin, tetracycline, and spectinomycin of 4405 pre-treatment gonococcal isolates from patients with uncomplicated gonorrhea. As compared to isolates studied in 1970-1971, recent United States isolates appeared equally sensitive to penicillin G and more sensitive to tetracycline. Relatively resistant strains were found throughout the country. We also studied 1974 patients, treated for uncomplicated gonorrhea according to the 1972 regimens recommended by the United States Public Health Service, to determine the relation between pretreatment minimum inhibitory concentrations and treatment results. For patients receiving the procaine penicillin-probenecid and ampicillin-probenecid regimens, minimum inhibitory concentrations to the treatment drugs were significantly higher in patients not cured than in those cured (P less than 0.01 fr penicillin and P less than 0.05 for ampicillin). In contrast, spectinomycin-treatment results appeared to be independent of the isolate's susceptibility to spectinomycin and other antibiotics.

OBJECTIVE: Recommendations for the use of antenatal antibiotics in obstetrics have increased in the past few years, especially for prophylaxis against group B streptococci, for prolongation of the latency time in patients with preterm premature rupture of the membranes, and as an adjuvant treatment in preterm labor. Our objective was to determine whether the use of antenatal ampicillin affects the incidence of and resistance of early-onset neonatal sepsis with organisms other than group B streptococci. STUDY DESIGN: A prospective cohort study was performed between January 1, 1991, and December 31, 1996. Every case of blood culture-proven neonatal sepsis was prospectively surveyed. The type of bacteria isolated, drug resistance, antenatal antibiotic use and treatment indication, gestational age at delivery, and other antenatal and outcome variables were gathered. Early-onset neonatal sepsis was defined as disease onset within 7 days after birth. RESULTS: A total of 42 cases of early-onset neonatal sepsis among 29,897 neonates delivered were found during the 6-year period. Of these, 15 cases were due to group B streptococci and 27 were the result of non-group B streptococcal organisms (21 gram-negative rods and 6 gram-positive cocci). Among the 27 non-group B streptococcal cases, 15 mothers had received antenatal ampicillin and 13 of the 15 bacterial isolates from these neonates (87%) were resistant to ampicillin, versus only 2 ampicillin-resistant isolates (17%) among the 12 cases in which no antenatal antibiotics were administered (P =.0004). Of the 15 mothers who were treated with ampicillin, 13 received more than 1 dose. In evaluating each year of the study, the overall administration of antibiotics to pregnant women in the antenatal period increased from <10% in 1991 to 16.9% in 1996. The incidence of early-onset neonatal sepsis with group B streptococci decreased during this time, whereas the incidence of early-onset sepsis with non-group B streptococcal organisms, especially Escherichia coli, increased. CONCLUSIONS: The increased administration of antenatal ampicillin to pregnant women may be responsible for the increased incidence of early-onset neonatal sepsis with non-group B streptococcal organisms that are resistant to ampicillin. At this time penicillin G, rather than ampicillin, is therefore recommended for prophylaxis against group B streptococci. In addition, future studies are needed to determine whether alternate approaches, such as immunotherapy or vaginal washing, could be of benefit.

78 patients with bacterial meningitis were evaluated in a prospective, randomised study comparing twice-daily ceftriaxone as single-drug therapy with ampicillin and chloramphenicol given every 6 h. The groups were comparable in age, sex, days of illness before admission, and bacterial colony counts in cerebrospinal fluid (CSF). The pathogens were Haemophilus influenzae type b (54 cases), streptococci (9 cases), meningococci (9 cases), and unknown (6 cases). In 40 CSF specimens obtained 4-12 h after initiation of therapy, cultures were negative in 57% of the ceftriaxone patients and in 42% of the others. The mean falls in the CSF bacterial colony counts were 4.7 and 5.0 log10 colony-forming units/ml, respectively. Mean bactericidal activity in CSF was significantly greater in the ceftriaxone than in the conventional treatment group at the beginning and end of therapy. There were no significant differences in clinical responses or in frequency of complications, except for mild diarrhoea, which occurred in 16 ceftriaxone patients and in 8 in the other group (p less than 0.05).