Level of maternal antibody required to protect neonates against early-onset disease caused by group B Streptococcus type Ia: a multicenter, seroepidemiology study.

Because of the difficulty of conducting efficacy trials of vaccines against group B streptococcus (GBS), the licensure of these vaccines may have to rely on studies that measure vaccine-induced antibody levels that correlate with protection. This study estimates the level of maternal antibody required to protect neonates against early-onset disease (EOD) caused by GBS type Ia. Levels of maternal serum IgG GBS Ia antibodies, measured by ELISAs in 45 case patients (neonates with EOD caused by GBS Ia) and in 319 control subjects (neonates colonized by GBS Ia but without EOD) born at > or =34 weeks gestation were compared. The probability of developing EOD declined with increasing maternal levels of IgG GBS Ia antibody (P = .03). Neonates whose mothers had levels of IgG GBS Ia antibody > or =5 microg/mL had an 88% lower risk (95% confidence interval, 7%-98%) of developing type-specific EOD, compared with those whose mothers had levels < 0.5 microg/mL. A vaccine that induces IgG GBS Ia antibody levels > or =5 microg/mL in mothers can be predicted to confer a high degree of type-specific immunity to EOD to their infants.

The effectiveness of risk-based intrapartum chemoprophylaxis for the prevention of early-onset neonatal group B streptococcal disease.

OBJECTIVE: Our purpose was to evaluate the effectiveness of a risk-based intrapartum antibiotic prophylaxis strategy for the prevention of early-onset neonatal group B streptococcal disease. STUDY DESIGN: Cases and controls were selected from infants born to women with one or more risk factors: preterm labor or rupture of membranes, prolonged rupture of membranes (>18 hours), fever during labor, or previous child with group B streptococcal disease. Cases were matched with controls by birth hospital and gestational age. Data abstracted from medical records were analyzed to estimate the effectiveness of intrapartum antibiotic prophylaxis. RESULTS: We analyzed data from 109 cases and 207 controls. Nineteen (17%) case versus 69 (33%) control mothers received an acceptable regimen of intrapartum antibiotic prophylaxis. In adjusted analyses, the effectiveness of intrapartum antibiotic prophylaxis was 86% (95% confidence interval, 66%-94%). When the first dose of antibiotics was given > or =2 hours before delivery, the effectiveness increased to 89% (95% confidence interval, 70%-96%); when it was given within 2 hours of delivery, the effectiveness was 71% (95% confidence interval, -8%-92%). Effectiveness was lowest in mothers with intrapartum fever (72%, 95% confidence interval, -9%-93%). On the basis of a 70% prevalence of maternal risk factors expected among cases in the absence of intrapartum antibiotic prophylaxis, we estimate that the risk-based strategy could reduce early-onset group B streptococcal disease by 60%. CONCLUSIONS: The risk-based approach to intrapartum antibiotic prophylaxis is effective in preventing early-onset group B streptococcal disease. To achieve the maximum preventive effect, the first dose of antibiotics should be administered at least 2 hours before delivery.

Linezolid for the treatment of community-acquired pneumonia in hospitalized children. Linezolid Pediatric Pneumonia Study Group.

OBJECTIVE: To determine the safety, tolerance, pharmacokinetics and efficacy of linezolid, a new oxazolidinone antibiotic in the treatment of community-acquired pneumonia in hospitalized children. DESIGN: A Phase II, open label multicenter study of intravenous linezolid followed by oral linezolid suspension, both at a dose of 10 mg/kg every 12 h. Efficacy was assessed at 7 to 14 days after the last dose of linezolid. PATIENTS: Children 12 months to 17 years old with community-acquired pneumonia admitted to the hospital of 14 participating centers. RESULTS: From July 21, 1998, through May 14, 1999, 79 children were enrolled and 78 received linezolid. Sixty-six children completed treatment and follow-up and were evaluable for clinical outcome. The median age of the evaluable patients was 3 years (range, 1 to 12 years); 47 were 2 to 6 years old. Pathogens were isolated from blood or pleural fluid cultures in 8 children: Streptococcus pneumoniae, 6 (2 penicillin-resistant); Group A Streptococcus, 1; methicillin-resistant Staphylococcus aureus, 1. Chest tubes were placed in 9 patients. The mean total duration of intravenous and oral administration was 12.2 +/- 6.2 days (range, 6 to 41 days). The mean peak and trough plasma concentrations of linezolid were 9.5 +/- 4.8 and 0.8 +/- 1.2 microg/ml, respectively. At the follow-up visit 7 to 14 days after the last dose of linezolid, 61 patients (92.4%) were considered cured including all the patients with proven pneumococcal pneumonia, one failed (methicillin-resistant Staphylococcus aureus) and 4 were considered indeterminate. The most common adverse effects in the intent to treat group were diarrhea (10.3%), neutropenia (6.4%) and elevation in alanine aminotransferase (6.4%). CONCLUSIONS: Linezolid was well-tolerated and could be considered an alternative to vancomycin for treating serious infections caused by antibiotic-resistant Gram-positive cocci in children pending results of additional studies.

Antibiotic susceptibility profiles for group B streptococci isolated from neonates, 1995-1998.

Antibiotic susceptibility profiles were analyzed for 119 invasive and 227 colonizing strains of group B streptococci isolated from neonates at 6 US academic centers. All strains were susceptible to penicillin, vancomycin, chloramphenicol, and cefotaxime. The rate of resistance to erythromycin was 20.2% and to clindamycin was 6.9%. Resistance to erythromycin increased in 1997. Type V strains were more resistant to erythromycin than were type Ia (P=.003) and type Ib (P=.004) strains and were more resistant to clindamycin than were type Ia (P<.001), type Ib (P=.01), and type III (P=.001) strains. Resistance rates varied with geographic region: in California, there were high rates of resistance to erythromycin and clindamycin (32% and 12%, respectively), and low rates in Florida (8.5% and 2.1%, respectively). Penicillin continues to be the drug of choice for treatment of group B streptococcus infection. For women who are penicillin intolerant, however, the selection of an alternative antibiotic should be guided by contemporary resistance patterns observed in that region.

Efficacy and safety of ampicillin/sulbactam and cefuroxime in the treatment of serious skin and skin structure infections in pediatric patients. UNASYN Pediatric Study Group.

BACKGROUND: Pediatric skin and skin structure infections are often polymicrobial and require empiric therapy effective against pathogens that may be resistant to many antimicrobial agents. The present study tested the efficacy and safety of a parenteral beta-lactam/beta-lactamase inhibitor combination, ampicillin/sulbactam, and a beta-lactamase-stable cephalosporin, cefuroxime, in serious pediatric skin and skin structure infections requiring hospitalization and parenteral antimicrobial therapy. METHODS: This was a multicenter, randomized, prospective, comparative open label trial that enrolled patients 3 months through 11 years of age. Patients received 150 to 300 mg/kg/day ampicillin/sulbactam in equally divided intravenous doses every 6 h. Cefuroxime was given in a dosage of 50 to 100 mg/kg/day either intravenously or intramuscularly in equally divided doses every 6 or 8 h. Maximum treatment was not to exceed 14 days. Patients could receive subsequent oral antimicrobial treatment at the investigator's discretion. RESULTS: At final evaluation for clinical efficacy, 78.0% (n = 46) of the 59 evaluable patients who received ampicillin/sulbactam were cured and 22.0% (n = 13) were improved. The respective values for the 39 evaluable patients treated with cefuroxime were 76.9% (n = 30) and 23.1% (n = 9). At the end of treatment all pathogens were eradicated from 93.2% (n = 55) of 59 patients treated with ampicillin/sulbactam and from 100% of 39 who received cefuroxime. There were no significant differences between treatments in clinical or bacteriologic efficacy. Both ampicillin/sulbactam and cefuroxime were well-tolerated. CONCLUSION: Both ampicillin/sulbactam and cefuroxime provide safe and effective parenteral antibiotic therapy in pediatric patients with serious skin and skin structure infections.

Capsular polysaccharide types of group B streptococcal isolates from neonates with early-onset systemic infection.

The distribution of serotypes of group B streptococci (GBS) isolated from 67 infants with early-onset sepsis are described. Case-infants were assembled from 13 hospitals across the United States from 15 July 1995 to 5 February 1997 through prospective active surveillance. The distribution of GBS serotypes was Ia, 40%; Ib, 9%; II, 6%; III, 27%; V, 15%; and nontypeable, 3%. Type V occurred more frequently in the northeast region (New York and New Jersey) than in other regions (29% vs. 9%, P = .06). Conversely, type III occurred significantly less frequently in the northeast region than other regions (10% vs. 35%, P = .04). GBS types Ia, III, and V accounted for 82% of the isolates. This report supports previous observations about the emergence of GBS type V, but our data caution that conclusions about serotype distributions based on one geographic location or on a small number of patients may not be generally applicable. Continued monitoring seems necessary for the design of a GBS vaccine.

Concentrations of procaine and aqueous penicillin in the cerebrospinal fluid of infants treated for congenital syphilis.

Penicillin concentrations in cerebrospinal fluid (CSF) were measured at various hours and days of treatment in 163 infants undergoing therapy for congenital syphilis. The CSF levels were compared for three treatment regimens. Aqueous penicillin G (A-PEN), 100,000 U/kg per day, was used in 23 infant, and a dosage of 200,000 U/kg per day was used in 40 patients; procaine penicillin G (P-PEN), 50,000 U/kg per day, was used in 100 children. Mean CSF penicillin levels were 0.416, 0.493, and 0.077 microgram/ml, respectively, in the three treatment groups. The mean CSF penicillin concentration among the 63 infants treated with either of the A-PEN regimens (0.465 microgram/ml) was significantly greater than the mean concentration (0.077 microgram/ml) among those treated with P-PEN (p < 0.001). Among those who received A-PEN, the difference in dosage was not associated with a significant difference in mean CSF penicillin concentration (p = 0.68). All the specimens obtained from patients who received A-PEN, but only 82% of those from patients who received P-PEN, had treponemicidal concentrations (> or = 0.018 microgram/ml). However, 33.3% (9/27) of specimens from infants who received P-PEN, tested between 18 and 24 hours after a dose, had CSF penicillin concentrations < 0.018 microgram/ml. These data suggest that administration of A-PEN may be the preferred therapy if CSF levels > 0.018 microgram/ml are desired, especially for infants with severe disease or congenital neurosyphilis.

Susceptibility of Haemophilus influenzae type b to ampicillin-sulbactam.

Seventy-five strains of Haemophilus influenzae type b, including 45 beta-lactamase-positive strains, were tested by MIC and time kill studies for susceptibility to ampicillin-sulbactam at various ratios. beta-Lactamase-negative strains were inhibited by lower concentrations of ampicillin-sulbactam than beta-lactamase-positive organisms. beta-Lactamase-negative strains showed a decrease in CFU per milliliter by a factor of 10(4) after a 24-h incubation with ampicillin-sulbactam. beta-Lactamase-positive isolates showed an initial decrease by a factor of up to 10(2) CFU per milliliter, but by the end of incubation these isolates grew to approximately the same cell density as the antibiotic-free control regardless of ampicillin-sulbactam ratios. Caution should be exercised in the use of this combination in treatment of meningitis, in which a high bacterial density is commonly encountered.

Poor performance of BACTEC NR 730 blood culture system in early detection of Neisseria meningitidis.

During an 8-month period at Children's Hospital, Oakland, Calif., a 9% rate for positive blood culture for children with Neisseria meningitidis meningitis was identified. The blood culture system used in each case was the BACTEC NR 730. This rate seemed significantly lower than previous rates (33 to 55%) (P.R. Dodge and M.N. Swartz, N. Engl. J. Med. 272:1003-1010, 1965; A.L. Hoyne and R.H. Brown, Ann. Intern. Med. 28:248-259, 1948; S. Levin and M.B. Painter, Ann. Intern. Med. 64:1049-1057, 1966). The low rate prompted our study. With 14 test strains, anaerobic and aerobic BACTEC bottles were evaluated for their ability to support and detect the growth of N. meningitidis. Sodium polyanetholesufonate (SPS) and inoculum size, two factors thought to affect the growth of N. meningitidis, were controlled for by use of bottles with and without SPS and by inoculum sizes simulating the magnitudes of bacteremia previously described for children infected with N. meningitidis (L.J. La Scolea, Jr., D. Dryja, T.D. Sullivan, L. Mosovich, N. Ellerstein, and E. Neter, J. Clin. Microbiol. 13:478-482, 1981). BACTEC failed to detect growth in aerobic bottles after 6 h of incubation, while 76 of 80 bottles (95%) showed growth when subcultured. At 24 h, BACTEC detected growth in only 29 of 80 bottles (36%); when subcultured, all 80 cultures grew confluently. At 48 h, BACTEC detected growth in the remaining 53 bottles. BACTEC failed to detect growth in anaerobic bottles at 6 h and at 1, 2, 4, and 5 days of incubation despite growth in subculture. Subcultures from bottles with tryptic soy broth with and without SPS showed growth in 63 to 76 bottles in 6 h and in all bottles after 24 h. The presence of SPS in BACTEC bottles had no effect on growth detection. On the basis of these studies and our clinical experience, we find the NR 730 system to be insensitive and unsuitable for detection of N.meningitidis in

Malassezia furfur: a cause of occlusion of percutaneous central venous catheters in infants in the intensive care nursery.

Growth of Malassezia furfur in the intravascular catheter used for administration of lipid emulsion resulted in occlusion of deep intravascular Silastic catheters in 12 infants in 2 intensive care nurseries. At the time of occlusion visible growth was noted in the clear catheter which was connected to the Silastic intravascular line. Five infants showed clinical signs suggestive of sepsis. The yield of M. furfur from blood cultures and catheter tips was low even when oil enrichment was used. The highest yield of M. furfur was found in the connecting catheter (11 of 11). The source from and the route by which M. furfur entered the catheter remain unclear. The potential portals of entry include the proximal and distal ends of the connecting catheter as well as the colonized skin of the infants and caretakers.

African sleeping sickness in the United States. Successful treatment with eflornithine.

The traditional treatment of African sleeping sickness (trypanosomiasis) with central nervous system involvement is an organic arsenical compound, melarsoprol, which is associated with severe and even life-threatening side effects. A polyamine biosynthesis inhibitor, eflornithine (chemical name, DL-alpha-difluoromethylornithine, supplied as monohydrochloride monohydrate), was used to treat a 3 1/2-year-old child with newly diagnosed severe trypanosomiasis that had been acquired more than two years previously in Zaire or the Congo. Treatment consisted of 300 to 400 mg/kg/d of eflornithine by continuous intravenous infusion for 25 days followed by 300 mg/kg/d of eflornithine by mouth divided in four equal doses daily for 17 days. The child's recovery was dramatic, with eradication of blood and cerebrospinal fluid parasites in the first week. Cerebrospinal fluid pleocytosis resolved completely. Her generalized adenopathy and fever gradually resolved. Severe ataxia, inability to walk or to change posture on her own, marked language regression, and lethargy all improved during and after her therapy. The drug was well tolerated; the only noted adverse effect was transient thrombocytopenia during the fourth week of therapy. Eflornithine was a safe and effective agent for treatment of trypanosomiasis with central nervous system involvement in this child.

Cerebral cysticercosis in a 22-month-old infant.

A case of cerebral cysticercosis is described in a 22-month-old infant from northern California who presented with a right-sided focal seizure. Unusual features were her young age; a single, enlarging, frontoparietal mass lesion; and apparent lack of history of exposure to an endemic area.

Transfusion-acquired hepatitis A in a premature infant with secondary nosocomial spread in an intensive care nursery.

An outbreak of hepatitis A involving 15 nurses, two premature infants, and the mother of one infant occurred in an intensive care nursery. The infants became infected after receiving blood transfusions from a donor who shortly thereafter experienced symptoms compatible with hepatitis A and was later found to have serologic evidence of acute hepatitis A. Hepatitis was not suspected clinically in the infants but was documented serologically. One of the infants had an ileostomy with liquid intestinal drainage. Her mother and most, if not all, of the nurses acquired hepatitis from this infant. All 15 nurses had contact with this infant, whereas only four nurses had contact with the second infant. The amount of contact nurses had with this infant clearly was related to their risk of infection. Nurses not actually assigned to this infant but who reported some contact had a significantly lower attack rate than those assigned to the infant. Among assigned nurses, those assigned to more than one shift had 4.7 times the risk of acquiring hepatitis than those assigned to one shift only. No specific nursing techniques or personal habits were documented as being significant risk factors in the infected group of nurses.