Jay M. Lieberman

Appropriate antibiotic use and why it is important: the challenges of bacterial resistance

Afterthe introduction of antibiotics in the mid-20th century, clinicians soon witnessed clinical failures secondary to bacterial resistance. Despite scientists’ efforts to synthesize more potent antibiotics during the last five decades, bacterial resistance continues to evolve, in large part because of the overuse and misuse of antibiotics. The treatment of several pathogens, including methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae and vancomycin-resistant enterococci, is problematic. New solutions are needed to preserve the activity of our current antibiotic armamentarium, to lower the overall risk of bacterial resistance and to successfully treat patients with resistant bacterial infections. Options include: development of new antibiotics to treat resistant organisms; vaccination to prevent infections; and improved use of antibiotics. Because bacteria will eventually develop means to avoid being killed by antibiotics, judicious use of antibiotics by all clinicians is imperative. Appropriate antibiotic use involves selection of a “targeted spectrum” antibiotic, as well as an appropriate dose and duration.

Enhanced antibody responses in infants given different sequences of heterogeneous Haemophilus influenzae type b conjugate vaccines

To evaluate the safety and immunogenicity of differing sequences of heterogeneous Haemophilus influenzae type b (Hib) conjugate vaccines, we randomly assigned 300 infants to one of six vaccination schedules. At 2, 4, and 6 months of age, subjects were given single or heterogeneous vaccines: Hib polysaccharide (PRP) conjugated to mutant diphtheria toxin (HbOC), PRP conjugated to outer-membrane protein of Neisseria meningitidis (PRP-OMP), or PRP conjugated to tetanus toxoid (PRP-T). No serious reactions were attributable to immunization with heterogeneous vaccines, and there were few significant differences in the rates of minor adverse reactions among groups. PRP-OMP was the only vaccine that induced an antibody response after the first dose, but significant booster responses were not seen after the second and third doses. Subjects given PRP-T vaccine responded well after two doses, but three doses of HbOC vaccine were needed for an equivalent antibody response. All the Hib vaccine schedules evaluated were immunogenic, and schedules initiated by PRP-OMP vaccine at 2 months of age, followed by two doses of either HbOC or PRP-T vaccine at 4 and 6 months of age, induced the highest antibody levels after each dose. Such schedules may be the best for protecting infants and children who are at greatest risk of having invasive Hib disease, such as American Indian children.

Aseptic meningitis in infants younger than six months of age hospitalized with urinary tract infections

Background. Aseptic meningitis associated with urinary tract infection (UTI) in young infants has not been described in detail in the literature. We performed a retrospective study to determine the incidence and clinical features of aseptic meningitis accompanying UTI. Methods. We retrospectively reviewed the medical records of all infants younger than 6 months of age hospitalized with a UTI at Miller Children’s Hospital from March 1995 through March 2000. UTI was defined as a urine culture growing ≥10 000 colony-forming units/ml of a single organism from a catheterized specimen or ≥100 000 colony-forming units/ml of a single organism from a bagged urine specimen. Meningitis was defined as a positive cerebrospinal fluid culture or cerebrospinal fluid with >35 white blood cells/mm3 in infants ≤30 days of age or with >10 white blood cells/mm3 in infants >30 days of age. Results. Of 386 infants with UTI, a lumbar puncture was performed in 260, and 31 (11.9%) had aseptic meningitis. One infant had bacterial meningitis. None of the 26 infants with UTI and bacteremia had aseptic meningitis. Two infants with meningitis had confirmed enteroviral infections, but aseptic meningitis did not occur more frequently in any particular month or during times of peak enteroviral activity. Conclusions. A cerebrospinal fluid pleocytosis is relatively common in hospitalized infants <6 months of age who have a UTI and usually does not reflect bacterial meningitis. Knowledge of this may prevent unnecessary courses of antibiotics for presumed bacterial meningitis and lead to evaluation for other possible causes of aseptic meningitis including viral or congenital infections.

Kinetics of maternal hepatitis a antibody decay in infants: implications for vaccine use.

We conducted a seroepidemiologic study to evaluate the kinetics of maternal hepatitis A antibody decay in infants. Serum samples obtained from 200 infants at 2 and 4 months of age were tested for hepatitis A antibody. Seventy-six infants (38%) were hepatitis A antibody-positive with a geometric mean antibody titer of 2634 mIU/ml. Samples collected at 4, 6 and/or 12 months of age showed seropositivity rates of 100, 95 and 39%, respectively. These data indicate that maternal antibody levels remained high through the first 6 months of life but decayed significantly by 12 months of age.

Nephrotoxicity associated with amphotericin B deoxycholate in neonates.

Background: The prevalence of nephrotoxicity in neonates receiving amphotericin B deoxycholate (amphoB) is not well-defined. While some studies report a lack of toxicity, others claim a frequency as high as 85%. Methods: We reviewed medical records of all infants ≤90 days of age in the neonatal intensive care unit who received at least 3 doses of amphoB between January 1990 and December 2004. A standardized form was used to collect demographic, therapeutic, microbiologic, and laboratory data for each patient. Nephrotoxicity was defined as a rise in serum creatinine (SCr) of at least 0.4 mg/dL any time during amphoB therapy. Results: A total of 92 infants met entry criteria. Median gestational age was 26 (range: 23–41) weeks and median birth weight was 863 (range: 546–4000) grams. Overall, 15 (16%) infants experienced nephrotoxicity, and 16 (17%) developed hypokalemia (<3.0 mmol/L). There were no differences between infants who did or did not develop nephrotoxicty in terms of gestational age, birth weight, gender, underlying medical conditions, or use of other potentially nephrotoxic medications. AmphoB exposure and duration of therapy were similar between infants who developed nephrotoxicity and those who did not, with a mean cumulative dose of 13.5 ± 9.6 mg/kg and duration of 16.3 ± 10.4 days. With the exception of 1 infant, the elevated SCr values resolved in all infants by the end of amphoB therapy. Conclusion: AmphoB administration does not appear to be associated with lasting measurable nephrotoxicity in neonates. Because of changes in serum creatinine and potassium, renal function and potassium levels should be monitored closely in infants receiving amphoB.

Management of community-associated methicillin-resistant Staphylococcus aureus infections in children.

In recent years, community‐associated methicillin‐resistant Staphylococcus aureus (CA‐MRSA) has emerged as a pathogen in children without established risk factors, and its prevalence in the United States is increasing. Although many CA‐MRSA infections are mild, primarily involving the skin and soft tissues, the organism can cause serious, invasive, and life‐threatening infections. To provide a comprehensive review of the epidemiology, clinical features, therapy, and prevention of CA‐MRSA infections in children, we performed MEDLINE (1966–January 2006) and Cochrane Library searches, and reviewed abstracts for relevance to S. aureus infections. Only articles pertaining to CA‐MRSA infections in pediatrics were closely examined. As a genetically distinct pathogen, CA‐MRSA is generally susceptible to multiple non–β‐lactam antimicrobials. The optimal treatment for CA‐MRSA infections in pediatric patients has not been well studied. Common antibiotics used include clindamycin, trimethoprim‐sulfamethoxazole, vancomycin, and rifampin. Rational empiric antimicrobial therapy for infections caused by S. aureus requires consideration of the possibility of methicillin resistance. The local prevalence and susceptibilities of CA‐MRSA, severity of infection, and individual risk factors should be considered in selecting treatment.

Impact of Empiric Antibiotic Use on Development of Infections caused by Extended-Spectrum ??-Lactamase Bacteria in a Neonatal Intensive Care Unit

Background: The neonatal intensive care unit at Miller Childrens Hospital changed from empiric use of cefotaxime and vancomycin (CEF) to tobramycin and vancomycin (TOB) for hospital-acquired infections in November 1999 because of an increase in infections caused by extended-spectrum β-lactamase (ESBL)-producing bacteria. The objectives of this study were to evaluate the incidence and impact of this change on the development of ESBL infections. Methods: We retrospectively reviewed medical records of infants who received CEF or TOB between January 1998 and December 2002. A standardized form was used to collect demographic data, information on antibiotic use, and culture results. Results: The mean gestational age and birth weight of the 250 infants were 28.8 ± 4.0 weeks and 1213.1 ± 662 g, respectively. There were no differences between infants who received CEF (N = 130) or TOB (N = 120) in terms of gestational age, birth weight, device use, invasive procedures, or prior antibiotic use. There were 11 ESBL infections. Infants in the CEF group were more likely than those in the TOB group to develop ESBL infection (7.8% versus 0.8%, P = 0.008). There were 11 deaths, with none attributed to ESBL infection. In a multivariate analysis, duration of prior ampicillin and gentamicin use and exposure to CEF were associated with ESBL infection [odds ratio (OR): 3.1, 95% confidence interval (CI): 1.28–7.49, P = 0.012; and OR: 33.7; 95% CI: 1.02–1136, P = 0.05, respectively]. Conclusions: The change from empiric use of CEF to TOB was associated with a significant decrease in the incidence of ESBL infections.

Fusobacterium osteomyelitis in a child with sickle cell disease.

Children who have sickle cell disease are at increased risk for osteomyelitis caused by Salmonella spp. and Staphylococcus aureus. We report a case of anaerobic osteomyelitis caused by Fusobacterium nucleatum in a child with sickle cell disease. The infection did not resolve with antibiotic therapy alone, but was cured after surgical debridement and hyperbaric oxygen therapy.

Universal hepatitis A vaccination in the United States: a call for action.

Previous hepatitis A recommendations for the United States targeted vaccination of at-risk individuals and children living in states and communities with consistently elevated rates of hepatitis A. Recommendations now call for routine hepatitis A vaccination of all children in the United States beginning at age 1 year (12–23 months). Currently, vaccination coverage rates for hepatitis A remain below rates of other routine childhood vaccines. Achieving a national immunization rate greater than 90% for the recommended 2 doses of hepatitis A vaccine would lessen disease impact throughout society. Routine childhood immunization against hepatitis A can be a highly effective strategy to reduce infection in children and community transmission of the virus, and the elimination of indigenous transmission of hepatitis A is an attainable goal.

Bacterial pneumonia in children

Pneumonia is the leading cause of death in children around the world. This article reviews the clinical manifestations, diagnoses, and management of the major causes of bacterial pneumonia in children of different ages. Major pathogens causing pneumonia in newborns include group B streptococcus, Listeria monocytogenes , and Chlamydia trachomatis , organisms that can infect infants born to mothers who have genital tract colonization. Streptococcus pneumoniae remains the most common cause of serious bacterial pneumonia in children, and the increasing incidence of penicillin-resistant strains can complicate therapy. Mycoplasma pneumoniae and Chlamydia pneumoniae are the most common causes of pneumonia in school-aged children. In most cases of bacterial pneumonia, a specific cause is not determined, and empiric therapy is based on the likely pathogens as determined by the childs age and the clinical presentation. Prevention, through simple measures such as breast-feeding and avoidance of exposure to passive smoke, as well as widespread use of available vaccines, is the most effective means of reducing the morbidity and mortality associated with bacterial pneumonia.