Antibacterial agents in pediatrics.

From low birth weight infants to adolescents, physiologic and developmental differences underlie the marked differences in pharmacokinetics and pharmacodynamics of antibacterial agents. Certain diseases, such as cystic fibrosis, also can alter these parameters. This article describes the principles of pharmacokinetics and pharmacodynamics that are unique to children and that characterize the clinical application of selected antibacterial agents to infectious diseases in children.

A prolonged outbreak of Pseudomonas aeruginosa in a neonatal intensive care unit: did staff fingernails play a role in disease transmission?

OBJECTIVES: To describe an outbreak of Pseudomonas aeruginosa bloodstream infection (BSI) and endotracheal tube (ETT) colonization in a neonatal intensive care unit (NICU), determine risk factors for infection, and make preventive recommendations. DESIGN: A 15-month cohort study followed by a case-control study with an environmental survey and molecular typing of available isolates using pulsed-field gel electrophoresis. SETTING AND PATIENTS: Neonates in the NICU of a university-affiliated children's hospital. INTERVENTIONS: Improved hand washing and restriction of use of long or artificial fingernails. RESULTS: Of 439 neonates admitted during the study period, 46 (10.5%) acquired P aeruginosa; 16 (35%) of those died. Fifteen (75%) of 20 patients for whom isolates were genotyped had genotype A, and 3 (15%) had genotype B. Of 104 healthcare workers (HCWs) from whom hand cultures were obtained, P aeruginosa was isolated from three nurses. Cultures from nurses A-1 and A-2 grew genotype A, and cultures from nurse B grew genotype B. Nurse A-1 had long natural fingernails, nurse B had long artificial fingernails, and nurse A-2 had short natural fingernails. On multivariate logistic regression analysis, exposure to nurse A-1 and exposure to nurse B were each independently associated with acquiring a BSI or ETT colonization with P aeruginosa, but other variables, including exposure to nurse A-2, were not. CONCLUSION: Epidemiological evidence demonstrated an association between acquiring P aeruginosa and exposure to two nurses. Genetic and environmental evidence supported that association and suggested, but did not prove, a possible role for long or artificial fingernails in the colonization of HCWs' hands with P aeruginosa. Requiring short natural fingernails in NICUs is a reasonable policy that might reduce the incidence of hospital-acquired infections.

Association of Bacteroides fragilis with childhood diarrhea.

Enterotoxigenic strains of Bacteriodes fragilis (ETBF) have recently been found to be associated with diarrheal illness in Apache and Bangladeshi children. This study was conducted to define the role of ETBF in diarrhea of children in an urban setting. Fecal specimens from 991 children with diarrhea and 581 asymptomatic age-matched controls were cultured for B. fragilis (BF). The isolates were tested for enterotoxin production using a human colonic epithelial cell line. BF was isolated from 318 (32.1%) of the patients and 123 (21.2%) of the controls (p < 0.001). In children < 1 year old which comprised about 50% of both patients and controls, the BF isolation rates were comparable (26.5% vs 25.7%; p = 0.812), contrasting with the significant difference in isolation rates for children > or = 1 year (37.6% vs 16.5%; p = < 0.001). Overall, ETBF were identified in 4.4% of patients and 3.1% of controls (p = 0.2). However, ETBF were significantly associated with diarrheal disease in children 1-5 years (5.4% vs 1.8%; p = 0.033) and 1-10 years (4.8% vs 1.5%; p = 0.021) in age. ETBF were isolated the year round and comprised 14.4% and 15% of the BF isolated from the patients and controls, respectively, suggesting that part of the indigenous BF are inherently enterotoxin producers. In this study, BF and ETBF were associated with diarrheal illness in children 1-10 years old.

Bacteremia due to Rochalimaea henselae in a child: practical identification of isolates in the clinical laboratory.

Two closely related species of Rochalimaea, Rochalimaea quintana and Rochalimaea henselae, are nutritionally fastidious but can be cultivated on bacteriologic media from the blood of patients with diverse clinical presentations. We report a case of culture-proven R. henselae bacteremia in a child with persistent fever. Serologic evidence of infection by R. henselae was ascertained by testing sera at two intervals for immunoglobulin G or immunoglobulin M antibodies by enzyme immunoassay and immunoblot. The case isolate and a collection of other strains (R. henselae, R. quintana, and related organisms) were used to test commercial identification systems for their comparative utility in the identification of Rochalimaea spp. on a practical basis. Of six systems designed for testing of either fastidious or anaerobic isolates of bacteria, the MicroScan Rapid Anaerobe Panel was the only system that distinguished R. henselae from R. quintana. Four of five others gave reactions that were unique within their data bases but did not distinguish Rochalimaea isolates at the species level.

Aeromonas species in aquaria: a reservoir of gastrointestinal infections?

To assess the role of aquaria in the epidemiology of aeromonas associated gastroenteritis, the prevalence and antibiotic susceptibility of aeromonads in ornamental aquaria were determined and compared to that of isolates obtained from patients with gastroenteritis. Thirty-eight (76%) of 50 aquaria, including those located in our hospital, yielded 61 isolates: 24 (39.3%) Aeromonas sorbria, 18 (29.0%) A. hydrophila, 15 (24.6%) A. caviae, and four (6.5%) which could not be speciated. In comparison, 41 (65%) of 63 faecal isolates were A. caviae. The aquarium isolates, in contrast to enteric isolates, were generally resistant to chloramphenicol, tetracycline, and trimethoprim/sulphamethoxazole. These findings indicate aquaria are unlikely sources of aeromonas-associated gastroenteritis, but their role as possible reservoirs for non-enteric infections with aeromonads needs to be defined.

Aeromonas-associated gastroenteritis in children.

During a 20-month period 55 strains of Aeromonas species were isolated from 53 children with diarrhea. The isolation rate of 2.5% for Aeromonas compared with the rates of 4.5% for Shigella, 3.3% for Salmonella, 2.7% for Campylobacter and 0.05% for Yersinia. In 45 children Aeromonas was the sole bacterial enteropathogen identified. Aeromonas was also isolated from 2 (0.5%) of 380 asymptomatic children. Despite its known lack of identifiable virulence properties, Aeromonas caviae was the most prevalent species, accounting for 69% of the isolates. None of the A. caviae strains produced cytotoxin by the 51Cr release assay and 12.5% were weakly enterotoxigenic by the infant mouse assay. All of the Aeromonas sobria and 71% of Aeromonas hydrophila were positive for both toxins. Ninety-two percent of the children with Aeromonas-associated diarrhea were younger than 3 years; 84% of the cases were seen between May and October. The majority of the children had an acute onset of watery diarrhea. Fever and vomiting were most commonly associated with the isolation of A. sobria. Eight children had chronic or intermittent diarrhea lasting for weeks to months before consultation; A. caviae was the isolate in all these cases. Several complications possibly related to Aeromonas intestinal infection were observed. These included Gram-negative bacteremia, intussusception, internal hernia strangulation, hemolytic uremic syndrome and failure to thrive in patients with chronic diarrhea.

Antimicrobial susceptibility of Aeromonas species isolated from patients with diarrhea.

In vitro susceptibility to 17 antimicrobial agents was determined for Aeromonas caviae, A. hydrophila, and A. sobria isolated from feces of patients with diarrhea. The three Aeromonas species shared a similar susceptibility pattern, except to cephalothin. Of the oral antimicrobial agents, the quinolones, followed by chloramphenicol, were most active; trimethoprim-sulfamethoxazole and tetracycline had good but variable activity.

In vitro antibacterial activities of antibiotics against Pseudomonas aeruginosa in peritoneal dialysis fluid.

Intraperitoneal antibiotics are used to treat Pseudomonas aeruginosa peritonitis, a serious complication of continuous ambulatory peritoneal dialysis. However, P. aeruginosa killing is often inefficient despite low MBCs. Broth dilution MIC/MBC and time kill curves of tobramycin, amikacin, netilmicin, azlocillin, piperacillin, ceftazidime, cefsulodin, and ciprofloxacin were determined in peritoneal dialysis fluid (PDF), buffered PDF, fluid recovered from patients on continuous ambulatory peritoneal dialysis (RPF), and cation-supplemented Mueller-Hinton broth. MBCs of all antibiotics were 8 to 16 times greater in PDF and RPF than in Mueller-Hinton broth or buffered PDF. Use of the time kill curve technique and Mueller-Hinton broth showed that aminoglycosides killed greater than or equal to 99.9% of P. aeruginosa at 1 h, ciprofloxacin killed greater than or equal to 99.9% at 2 h, and beta-lactams killed greater than or equal to 99.9% at 6 h. In contrast, killing was not demonstrated in PDF by any drug at 6 h and by aminoglycosides only at 24 h. Bactericidal activity was optimal in RPF for ciprofloxacin at 1 h and for aminoglycosides at 2 h; bactericidal activity was not demonstrated in RPF with any beta-lactam (no kill by penicillins; less than 99% kill by cephalosporins). Slow bacterial growth, increased protein binding, and glucose concentrations and other inhibitors may interfere with beta-lactam activity in RPF. These considerations and reported clinical failures and toxicity of aminoglycoside therapy warrant further study of quinolones and drug combinations in P. aeruginosa peritonitis.

Campylobacter enteritis. A 3-year experience.

Campylobacter jejuni was isolated from 135 infants and children seen at the Oklahoma Children's Memorial Hospital over a 3-year period. The comparative frequency of isolation of C. jejuni, Salmonella, and Shigella were 1.5 percent, 2.2 percent, and 3.1 percent, respectively. Campylobacter enteritis was most prevalent during the warm months from May to October, peaking in July. Seventy percent of the afflicted children were 2 years old or younger; only 13 percent were older than 5 years. There were the usual clinical presentations (acute onset of diarrhea, fever, abdominal pain, and bloody stools) of Campylobacter enteritis, but other, less common, patterns also were seen. These included chronic diarrhea without significant systemic manifestations; asymptomatic bloody stools, particularly in neonates; and fever and abdominal pain without diarrhea. Severe complications included hemolytic-uremic syndrome, sepsis associated with septic arthritis and osteomyelitis, and failure to thrive.

Hemophilus influenzae type b meningitis in infant rabbits. Pathogenesis and therapy.

A model of human Hemophilus influenzae type b meningitis was developed in infant rabbits infected intranasally. The pathogenesis and course resembled that in human beings; bacteremia was followed by meningitis with a high mortality. Pretreatment of the nasopharyngeal mucosa with 0.5% trypsin or normal saline significantly increased the rate of bacteremia. Death was age related. Intranasal challenge with type f and nontypeable H influenzae was associated with transient bacteremia. Our results suggest that factors on the respiratory tract epithelial cell surface influence colonization and infection with H influenzae type b and confirm the importance of other host and parasite factors. Intravenous aztreonam resulted in a peak CSF concentration that was 6% to 7% of the serum concentration in infected meninges but only 2% to 3% in normal meninges. Aztreonam reduced mortality in established H influenzae type b meningitis from 88% in untreated animals to 9%.

Haemophilus influenzae b bacteremia and meningitis in infant rabbits after intranasal inoculation.

A suitable model of Haemophilus influenzae meningitis will facilitate better understanding of the pathophysiology, therapy, and prevention of the disease and its sequelae. Bacteremia and meningitis were induced in infant New Zealand white rabbits by intranasal inoculation of H. influenzae type b. Intranasal trypsin prior to challenge significantly increased (p = 0.002) the rate of bacteremia from 64% (7/11) to 100% (45/45). In the trypsin-treated group, H. influenzae b was isolated from the CSF of 89% (25/28) of 17- to 21-day-old rabbits and from 76% (13/17) of 23- to 30-day-old animals, p = 0.3; fatality rates were 88% and 31%, respectively, p = 0.001. Bacteremia developed within 24 hr of inoculation and meningitis within 96 hr. Death occurred 1 to 7 days after the development of meningitis. Histologic evidence of nasopharyngitis and meningitis was found at autopsy. The intranasal route of infection, the age-dependent outcome, the size of the animal, and its low cost and availability make the infant rabbit an appropriate model of H. influenzae b meningitis.

Prevalence of Chlamydial antibodies in children.

Humoral antibody to Chlamydia trachomatis was determined in 820 infants and children. Of 120 newborns, 63 (52.5%) had indirect immunofluorescence titers of 1:8 or more to C trachomatis (L-2 strain) in the cord blood. Among the 700 infants and children, a progressive increase in seropositivity was observed: 5% for 1- to 2-years-olds, 25% for 3- to 6-year-olds, and 43% for 7- to 15-year-olds. Seropositivity rates were not related to sex or race; however, significantly higher titers were observed in female compared with male subjects and in blacks compared with whites. These data suggest that C trachomatis infection occurs commonly in children. The nature of the illness, if any, preceding seroconversion is unknown and needs to be elucidated.

Increased cerebrospinal fluid free amino acid concentrations in children with bacterial meningitis.

19 free amino acids were measured by Durrum high pressure chromatography in the cerebrospinal fluid of 19 children, 9 with and 10 without bacterial meningitis. Each of the amino acids, except for gamma-amino butyric acid, was significantly increased in meningitis. Values were elevated upon admission of these patients to the hospital, but the highest concentration for most of the amino acids was noted in specimens collected 24-48 h after initiation of antibiotic treatment. Upon the completion of successful antibiotic therapy, the amino acid concentrations returned to normal or near normal levels.