The threat of biological terrorism: a public health and infection control reality.

Bioterrorism is an emerging public health and infection control threat. Potential biological agents include smallpox, anthrax, plague, tularemia, botulinum toxin, brucellosis, Q fever, viral encephalitis, hemorrhagic fever, and staphylococcal enterotoxin B. An understanding of the epidemiology, clinical manifestations, and management of the more likely candidate agents is critical to limiting morbidity and mortality from a biological event. Effective response requires an increased index of suspicion for unusual diseases or syndromes, with prompt reporting to health authorities to facilitate recognition of an outbreak and subsequent intervention. Hospital epidemiology programs will play a crucial role in this effort.

Nosocomial pneumococcal infection: an outbreak.

When an outbreak of pneumococcal disease occurs an institution--be it a hospital, nursing home, day care center, or other facility--management includes treatment of affected cases and prevention of new cases. Patients and staff should be tested for nasopharyngeal carriage and their vaccination status ascertained. Antibiotic use should be reviewed, especially if the causative strain is resistant.

Repeated invasive pneumococcal infections in young children without apparent underlying immunodeficiency.

During a 30-month interval at LeBonheur Children's Medical Center, 394 patients had a blood or cerebrospinal fluid culture positive for Streptococcus pneumoniae. Sixteen of these episodes (4%) were repeated infections; 6 of these 16 patients had sickle cell disease. Six of the remaining 10 patients had immunologic evaluations of varying completeness; no immunodeficiency was identified by these tests or on follow-up. Nine of the ten previously healthy patients with repeated pneumococcal disease were less than 2 years of age. In our experience, repeated invasive pneumococcal infections in otherwise healthy young children were relatively common (10/394, or 2.5% of patients with invasive pneumococcal infections) and did not indicate the presence of an unsuspected immunodeficiency.

Inter- and intra-patient sequence diversity among parainfluenza virus-type 1 nucleoprotein genes.

Parainfluenza viruses (PIV) have been categorized into four discrete types (types 1-4), based on antigenic similarities. Here is described an evaluation of nucleoprotein (NP) sequence variability among nine patients infected with the type 1 virus. The examination of short segments of the NP sequence was sufficient to define significant variability both within and between patient samples. These data, in conjunction with previous studies of hemagglutinin-neuraminidase and fusion protein sequences from PIV-infected patient populations suggest a lack of absolute stability among isolates within each virus type. Potentially, antigenic variability exists to the extent that an immune response elicited toward one isolate may not be fully protective against another of the same type. Thus, sequence variability could contribute to natural re-infections with PIV, as well as to previous vaccine failures. Results highlight the importance of analyzing viruses that break through vaccine-induced immunity, in order to measure the influence of virus diversity on PIV vaccine outcome.

The clinical impact of resistance in the management of pneumococcal disease.

The prevalence of drug-resistant Streptococcus pneumoniae (DRSP) has increased worldwide. Although unfavorable outcomes in meningitis due to DRSP have been well-described, the clinical impact of DRSP on other manifestations of pneumococcal infection warrants further study. Empiric combination vancomycin and extended-spectrum cephalosporin (cefotaxime or ceftriaxone) therapy is indicated for the following clinical indications: purulent meningitis, life-threatening pneumonia, and suspected sepsis in patients predisposed to invasive pneumococcal disease, for example, sickle cell disease, HIV infection, and nephrotic syndrome. In addition to clinical management issues, other implications of the emergence of DRSP include identification of resistant strains, local and national surveillance, and prevention. Preventive measures include judicious antibiotic use, appropriate use of the currently available 23-valent pneumococcal vaccine, and development and implementation of a protein-conjugate vaccine.

Serious infections due to penicillin-resistant Streptococcus peneumoniae in two children with nephrotic syndrome.

Children with nephrotic syndrome are susceptible to the development of invasive bacterial infections, particularly those caused by Streptococcus peneumoniae. Recently, penicillin-resistant pneumococcal infections in children have occurred in increased frequency in some regions. We have seen two children with nephrotic syndrome who developed penicillin-resistant pneumococcal bacteremia and/or peritonitis. A change in the initial therapy from penicillin in the usual dose in these patients must be considered.

Risk factors for carriage of drug-resistant Streptococcus pneumoniae among children in Memphis, Tennessee.

OBJECTIVES: To determine risk factors for carriage of drug-resistant Streptococcus pneumoniae to understand better the factors promoting spread of these isolates. STUDY DESIGN: We obtained medical and demographic information and nasopharyngeal swab specimens from 216 children less than 6 years old with upper respiratory tract infections, seeking medical care at five Memphis, Tenn, study sites. We evaluated risk factors for carriage of penicillin-nonsusceptible S. pneumoniae (NSSP) among 100 children with S. pneumoniae isolates. Patterns of antimicrobial prescription were recorded for enrolled children. RESULTS: Independent risk factors for carriage of NSSP included an increased number of antimicrobial treatment courses during the previous 3 months and white race. Day care attendance approached statistical significance (p = 0.07). Most children with upper respiratory tract infection received a prescription for antimicrobial drugs. These prescriptions were more common for white children than for black children. CONCLUSIONS: Increased use of antimicrobial drugs enhances the risk of carriage of NSSP. This may contribute to the higher risk among white children of NSSP infection; however, after control for antimicrobial use, white children were still at an increased risk of infection with NSSP, possibly through greater exposure to resistant strains.

Relationship of MICs to efficacy of cefotaxime in treatment of Streptococcus pneumoniae infections.

In June 1993, the National Committee for Clinical Laboratory Standards (NCCLS) recommended stringent new interpretive guidelines for antibiotics indicated for Streptococcus pneumoniae meningitis. To assess the predictive values of the recommended breakpoints, retrospective data were collected from patients who had S. pneumoniae infections and were treated with cefotaxime monotherapy. Susceptibilities based on the NCCLS interpretative categories were compared with clinical and bacteriologic outcomes. In 76 evaluable patients, the most common infections were bacteremia-septicemia (n = 49), meningitis (n = 37), and lower respiratory tract infection (n = 14). Under the NCCLS breakpoints proposed in 1993, 55 isolates would have been classed as susceptible to cefotaxime (MIC, < or = 0.25 microgram/ml), 18 would have been classed as intermediate (MIC, 0.5 to 1.0 microgram/ml), and 2 would have been classed as resistant (MIC, > or = 2 micrograms/ml). Of 75 cefotaxime-treated patients for whom cefotaxime MICs were recorded, 73 were clinically cured or improved (37 of 37 with meningitis and 36 of 38 with other infections). One case of bacteremia and one case of bone-and-joint infection were scored as therapeutic failures because initial monotherapy had to be modified because of an adverse drug reaction. Excluding these patients, there were 18 patients infected with S. pneumoniae that would have been classed as not fully susceptible (i.e., MICs > or = 0.5 microgram/ml); all of these patients were cured or improved. The results of this analysis demonstrate that successful treatment with cefotaxime did not correlate well with the guidelines for the susceptibility of pneumococcal isolates to either penicillin or cefotaxime established by the 1993 NCCLS breakpoint recommendations. Because of this study and other similar findings, the NCCLS adopted more clinically relevant guidelines in 1994.

Penicillin- and cephalosporin-resistant strains of Streptococcus pneumoniae causing sepsis and meningitis in children with sickle cell disease.

OBJECTIVE: We investigated the possibility that antimicrobial-resistant pneumococci were causing invasive disease in children with sickle-cell disease (SCD). STUDY DESIGN: Records of all children with SCD observed at the Mid-South Sickle Cell Center (MSSCC) at LeBonheur Children's Medical Center were reviewed from January 1990 to June 1994. Children with SCD and pneumococcal sepsis were identified. The Streptococcus pneumoniae isolates from these children were examined for serotype and antimicrobial susceptibilities. Two additional children not observed in the MSSCC had pneumococcal sepsis caused by penicillin-resistant isolates and were also included. RESULTS: Antimicrobial susceptibility testing of the six penicillin-resistant isolates revealed that four were resistant to trimethoprim-sulfamethoxazole, two to erythromycin, and one to clindamycin. The two isolates that were resistant to ceftriaxone also were multiply resistant. From the MSSCC, 26 children had pneumococcal sepsis during the 4 1/2-year period studied. Five of these children (19%) died. Four (15%), including one who died, were infected with penicillin-resistant strains. CONCLUSION: Pneumococcal sepsis, meningitis, and infections of other foci in children with SCD may be caused by S. pneumoniae that is resistant to one or more antimicrobial agents, including penicillin. The addition of vancomycin to the antibiotics currently used for initial management should be considered in areas where the antibiotic resistance of S. pneumoniae is prevalent.

Prophylactic antibiotic use in pediatric cardiovascular surgery: a survey of current practice.

There is little information on prophylactic antibiotic practice in pediatric cardiovascular surgery. A consensus prophylactic antibiotic practice, if identified, might serve as a standard to which alternative prophylactic antibiotic practice could be compared. We surveyed North American academic centers with pediatric cardiovascular surgery programs regarding their standard antimicrobial prophylaxis regimens, duration of prophylaxis and modification of prophylaxis for lesion, patient age or medical device considerations. Forty-three (81%) of 53 centers responded; not all responses were complete. Monotherapy was used by 39 (91%) of 43; 38 (97%) of 39 used a 1st or 2nd generation cephalosporin (cefazolin 24, cefamandole 8, cefuroxime 4, cephapirin 1, unspecified 1) and 1 of 39 used vancomycin. Only 4 (9%) of 43 used 2 antibiotics. Prophylactic antibiotics were started pre- or intraoperatively by 41 of 43 centers and discontinued within 2 days by 25 of 37. Prophylactic antibiotics were often continued while thoracostomy tubes (29 of 43), mediastinal tubes (31 of 43) or transthoracic vascular catheters (22 of 43) were in place, but usually not for endotracheal tubes (6 of 43), arterial (9 of 43) or percutaneous central venous (13 of 43) catheters or temporary pacing wires (6 of 43). Our survey indicates that the consensus prophylactic antibiotic regimen for pediatric cardiovascular surgery is monotherapy with a first or second generation cephalosporin, used for < or = 2 days or until transthoracic medical devices are removed.

Invasive group B streptococcal disease in children beyond early infancy.

There is little information available on invasive group B Streptococcus (GBS) infection in pediatric patients older than 3 months of age. Review of infection control records at LeBonheur Children's Medical Center from January 1, 1986, to June 30, 1993, identified 143 patients with a positive GBS culture from normally sterile body fluid. Medical records of 18 (13%) patients > 3 months old with their first GBS infection were reviewed. Age range was 15 weeks to 18 years (median age, 13 months). Ten were black and 11 were girls. Five infants had a history of premature birth and 2 infants were infected with human immunodeficiency virus. The serotype distribution of 12 available GBS isolates was 4 type III, 2 each type V and Ia and 1 each type Ia/c, Ib/c, II and II/c. Bacteremia without a focus (9 patients) was the most common clinical manifestation. All 4 type III isolates were associated with bacteremia. One infant with human immunodeficiency virus infection had sepsis and bullous desquamation; a toxin-producing type V strain was isolated from her blood. Two adolescents with ventriculoperitoneal shunts had meningitis, including one whose cerebrospinal fluid also grew a type V strain. Other clinical manifestations were septic arthritis, endocarditis (Ia, II/c), central venous catheter (Ia/c) and ventriculostomy infections.

Age-related development of human memory T-helper and B-cell responses toward parainfluenza virus type-1.

Human parainfluenza-1 virus (hPIV-1) infections are a major cause of respiratory illness in young children. While children and adults are each susceptible to hPIV-1 infection, the clinical symptoms in adults are mild and hospitalizations are rare. One explanation for the differences in disease severity is that immune memory responses are simply inferior in children as compared to adults and cannot counter virus growth. Alternatively, it has been suggested that immune (particularly T-helper (TH) cell) responses toward respiratory viruses are superior in children versus older individuals, and that these responses contribute to, rather than protect from, disease symptoms. As a test of these possibilities, we analyzed hPIV-1-specific T-helper (TH) and B-cell memory responses among individuals of various ages, including children hospitalized with hPIV-1-induced croup. Experiments revealed: (1) hPIV-1-specific B-cell and class-II restricted TH-cell proliferative responses were present in all tested adults. (2) TH-cells responded to internal viral proteins as well as to the external glycoprotein, hemagglutinin-neuraminidase. (3) Immune responses were highly cross-reactive with Sendai virus. (4) Memory B-cell and TH-cell responses were extremely poor in young children, inclusive of children tested upon hospital entry for hPIV-1-induced croup. In total, results did not support the theory that naturally induced hPIV-specific memory responses cause respiratory illness. Rather, results showed a correlation between memory and a good clinical outcome and highlighted Sendai virus as a strong candidate for an hPIV-1 vaccine.