Discriminators between hantavirus-infected and -uninfected persons enrolled in a trial of intravenous ribavirin for presumptive hantavirus pulmonary syndrome.

To provide a potentially therapeutic intervention and to collect clinical and laboratory data during an outbreak of hantavirus pulmonary syndrome (HPS), 140 patients from the United States with suspected HPS were enrolled for investigational intravenous ribavirin treatment. HPS was subsequently laboratory confirmed in 30 persons and not confirmed in 105 persons with adequate specimens. Patients with HPS were significantly more likely than were hantavirus-negative patients to report myalgias from onset of symptoms through hospitalization, nausea at outpatient presentation, and diarrhea and nausea at the time of hospitalization; they were significantly less likely to report respiratory symptoms early in the illness. The groups did not differ with regard to time from the onset of illness to the point at which they sought care; time from onset, hospitalization, or enrollment to death was significantly shorter for patients with HPS. At the time of hospitalization, patients with HPS more commonly had myelocytes, metamyelocytes, or promyelocytes on a peripheral blood smear, and significantly more of them had thrombocytopenia, hemoconcentration, and hypocapnia. Patterns of clinical symptoms, the pace of clinical evolution, and specific clinical laboratory parameters discriminated between these 2 groups.

Intravenous ribavirin for hantavirus pulmonary syndrome: safety and tolerance during 1 year of open-label experience. Ribavirin Study Group.

Intravenous ribavirin was provided non-selectively for investigational open-label use among persons with suspected hantavirus pulmonary syndrome (HPS) in the United States between 4 June 1993 and 1 September 1994. Therapy was initiated prior to laboratory confirmation of hantavirus infection because most deaths from HPS occur within 48 h of hospitalization. Thirty patients with confirmed HPS, 105 patients without HPS and 5 patients without adequate diagnostic testing for HPS were enrolled. This observational study arguably provides the most complete information available on ribavirin-associated adverse effects. Although ribavirin was generally well tolerated, 71% of recipients became anaemic and 19% underwent transfusion. An apparent excess of hyperamylasaemia/pancreatitis was either therapy-associated or due to enrollment bias. The 30 enrolled HPS patients had a case-fatality rate of 47% (14/30). It is not possible to assess efficacy with this study design. However, comparison of survival curves for the 30 enrolled HPS patients and 34 patients who developed HPS during the same time period but were not enrolled did not suggest an appreciable drug effect. A randomized, placebo-controlled trial that enrolls patients during the prodrome phase would be necessary to assess the efficacy and further define the safety of intravenous ribavirin for HPS.

Growth failure, intracranial calcifications, acquired pancytopenia, and unusual humoral immunodeficiency: a genetic syndrome?

We report on two children who may represent a novel syndrome consisting of a deficiency of immunoglobulin-bearing B lymphocytes and serum antibody, deficient intrauterine and/or postnatal growth, intracranial calcifications, and acquired pancytopenia. Poor growth, intracranial calcifications, developmental delay, and hematological abnormalities are common manifestations of congenital infection. However, humoral immunodeficiency is not characteristic in these infections, and no infection was found on extensive evaluation. Rare genetic syndromes may mimic intrauterine infections and may also include immunodeficiency. However the children reported here lack important characteristics or share distinctive manifestations not described in these disorders. Infants presenting with apparent congenital infections in whom a specific infectious cause cannot be identified should be followed carefully with immunological evaluations since this disorder may be progressive and considerable morbidity is attributable to hematological and immunological manifestations.

Aerosolized ribavirin treatment of respiratory syncytial virus infection in infants hospitalized during an epidemic.

Thirty-three infants with predisposing conditions and/or severely symptomatic with respiratory syncytial virus (RSV) infection were treated with aerosolized ribavirin during a 12-week period at Oklahoma Children's Memorial Hospital. These patients were compared with 97 untreated patients with RSV infection hospitalized during the same epidemic. Despite preconditions which selected for a more seriously ill treatment group, patients who received ribavirin showed prompter resolution of the illness than did untreated controls. Greatest clinical improvement in treated patients occurred between the first and second days of ribavirin therapy; mean ribavirin treatment duration was 4.5 days. Ten of 22 ribavirin-treated patients continued to excrete RSV after conclusion of antiviral therapy. No adverse hematologic, renal or metabolic effects occurred with ribavirin therapy. Our experience with ribavirin therapy during a major epidemic confirms and extends the results of previous controlled evaluations demonstrating this treatment safe and effective in high risk and seriously ill infants with RSV bronchiolitis and bronchopneumonia.

Detection of vancomycin-resistant enterococci colonization in a children's hospital.

BACKGROUND: Vancomycin-resistant enterococci (VRE) are important nosocomial pathogens in many hospitals. The true prevalence of VRE in pediatric hospitals is not known. METHODS: A surveillance study was performed at a pediatric tertiary care medical center by using vancomycin-containing screening media. RESULTS: Six children (of 112 screened) were found to be colonized with VRE. Colonized patients had a history of receiving broad-spectrum antimicrobial agents. CONCLUSION: In the absence of VRE infections, surveillance studies can help determine the extent of VRE colonization and support infection control measures.

Nosocomial mumps: report of an outbreak and its control.

BACKGROUND: Mumps is a relatively uncommon disease in the United States, and nosocomial transmission of mumps is rare. METHODS: When a recently arrived Mexican immigrant became ill with mumps in a pediatric hospital in the United States, control measures and careful secondary case surveillance were instituted. Outbreak control included isolation of the patient with symptoms, seclusion of patients potentially incubating mumps virus, and immunization of susceptible patients and health care workers. RESULTS: A 3-year-old patient showed symptoms of mumps 18 days after onset of illness in the index patient. Two employees, a physical therapist and a nurse, became ill with mumps 20 and 28 days after the onset of illness in the index patient. No other hospital or community cases of mumps were identified. CONCLUSIONS: Outbreak control measures were incompletely successful in stopping the spread of mumps. Preadmission immunization of all patients and mumps-specific screening and vaccination of hospital employees might be indicated in such a situation, but such measures are neither easy nor inexpensive.

Bacillus cereus infections among oncology patients at a children's hospital.

BACKGROUND: Bacillus cereus can cause severe infections in immunocompromised persons. METHODS: We report 3 cases of bacteremia/septicemia (1 fatal) among oncology patients in a children's hospital. Because all cases occurred during a 10-day period, a common source outbreak was suspected. An epidemiologic investigation was performed. Molecular comparison of patient and environmental isolates was performed by using pulsed-field gel electrophoresis. RESULTS: After an extensive investigation, no common hospital source could be found. Pulsed-field gel electrophoresis proved that the isolates were not related. CONCLUSION: Sporadic infections in immunocompromised persons do occur and can be associated with significant morbidity.

Clinicians' response to computerized detection of infections.

OBJECTIVE: To analyze whether computer-generated reminders about infections could influence clinicians' practice patterns and consequently improve the detection and management of nosocomial infections. DESIGN: The conclusions produced by an expert system developed to detect and manage infections were presented to the attending clinicians in a pediatric hospital to determine whether this information could improve detection and management. Clinician interventions were compared before and after the implementation of the system. MEASUREMENTS: The responses of the clinicians (staff physicians, physician assistants, and nurse practitioners) to the reminders were determined by review of paper medical charts. Main outcome measures were the number of suggestions to treat and manage infections that were followed before and after the implementation of COMPISS (Computerized Pediatric Infection Surveillance System). The clinicians' opinions about the system were assessed by means of a paper questionnaire distributed following the experiment. RESULTS: The results failed to show a statistical difference between the clinicians' treatment strategies before and after implementation of the system (P: > 0.33 for clinicians working in the emergency room and P: > 0.45 for clinicians working in the pediatric intensive care unit). The questionnaire results showed that the respondents appreciated the information presented by the system. CONCLUSION: The computer-generated reminders about infections were unable to influence the practice patterns of clinicians. The methodologic problems that may have contributed to this negative result are discussed.

Contamination of enteral nutrition systems during prolonged intermittent use.

Two related studies were done to determine the incidence of bacterial contamination in enteral delivery systems that were used for 15 and 7.5 hr, rinsed after each use, and reused daily in vitro for 7 and 5 days, respectively. In the first study, systems infusing either a premixed formula (Ensure) or a hand-mixed formula (Vivonex) did not show bacterial growth until the 4th day, 1.0-2.0 X 10 colony-forming units per milliliter (CFU/ml) of Staphylococcus epidermidis. Thereafter there was sporadic growth of different organisms but never increasing growth during the 7 days of infusion. In the second study, systems with Ensure were initially contaminated with Staphylococcus aureus and Escherichia coli and reused for 5 days. S. aureus was eliminated by rinsing, but E. coli persisted in the delivery system at concentrations of 10(3)-10(6) CFU/ml. We conclude that clean enteral nutrition systems can be rinsed after short-infusion periods and reused up to 7 days in vitro without significant contamination; however, once a bag has become heavily contaminated some bacteria cannot be eradicated from the system by rinsing.

Proper use of the clinical microbiology laboratory.

The interaction between clinicians and microbiology laboratory staff has to be one of mutual benefit. The more the laboratory personnel know about your patients, the more meaningful and thorough will be the results. Communication is the key to success. Visit the microbiology laboratory and get to know the staff. The clinician also needs to be familiar with and use the most commonly used diagnostic tests for individual bacterial pathogens appropriately.

In vitro activity of meropenem, imipenem, cefepime and ceftazidime against Pseudomonas aeruginosa isolates from cystic fibrosis patients.

We studied 67 Pseudomonas aeruginosa isolates from cystic fibrosis patients, and compared their in vitro susceptibility to two carbapenems (meropenem and imipenem) and two cephalosporins (cefepime and ceftazidime). The carbapenems were more effective in vitro than the cephalosporins: 92.5% of isolates were susceptible to the former and 77.6% to the latter. Essentially no difference was found between meropenem and imipenem. More discrepancies were seen between cefepime and ceftazidime: four of 67 isolates (6.0%) were more susceptible to cefepime than to ceftazidime, while eight (11. 9%) were more susceptible to ceftazidime than to cefepime.

Comparative efficacy and safety of cefprozil (BMY-28100) and cefaclor in the treatment of acute group A beta-hemolytic streptococcal pharyngitis.

Cefprozil (BMY-28100) is a semisynthetic cephalosporin with broad-spectrum antibacterial activity and prolonged serum elimination half-life allowing for once-a-day oral administration. In vitro, cefprozil demonstrates excellent activity against Staphylococcus aureus, Streptococcus pyogenes, Haemophilus influenzae, and Moraxella catarrhalis. Cefprozil (500 mg once daily) was compared to cefaclor (250 mg three times daily) in an open, randomized, comparative trial for the treatment of acute group A beta-hemolytic streptococcal pharyngitis. Ninety-four patients were enrolled in this study; 53 patients were evaluable for clinical and bacteriological response assessment. Seventy-eight patients were evaluable for safety assessment. Three patients (all in the cefprozil treatment group) required disenrollment because of side effects, mainly nausea. Clinical and bacteriological responses were comparable for both study drugs. Leukopenia and nausea, the most common side effects observed, were more common in the cefprozil-treated group. Cefprozil appears to be an appropriate alternative to cefaclor for the treatment of acute group A beta-hemolytic streptococcal pharyngitis. However, because of the small number of patients eligible for efficacy assessment, a large type II (beta) error was expected in our study, which may have resulted in a potential failure to detect a difference between both treatment groups. A larger study would be required to determine the proper role of cefprozil in the treatment of group A beta-hemolytic streptococcal infections.

Computerized detection of nosocomial infections in newborns.

Hospital-acquired infections are responsible for an increase in patient mortality and costs. Their detection is essential to permit better infection control. We developed an expert system specifically to detect infections in pediatric patients. The expert system is implemented at LDS Hospital that has a level three newborn intensive care unit and well baby units. We describe how the knowledge base of the expert system was developed, implemented, and validated in a retrospective study. The results of the system were compared to manual reviewer results. The expert system had a sensitivity of 84.5% and specificity of 92.8% in detecting hospital-acquired infections when compared to a physician reviewer. The Cohen's kappa between the expert system and the physician reviewer was 0.62 (p < .001).

Comparative efficacy and safety of cefprozil and cefaclor in the treatment of acute uncomplicated urinary tract infections.

Cefprozil is a new oral semi-synthetic cephalosporin with broad antibacterial spectrum and prolonged serum elimination half-life. In vitro, cefprozil demonstrates excellent activity against common urinary tract pathogens such as Escherichia coli and Klebsiella pneumoniae. Cefprozil, 500 mg once a day, was compared to cefaclor, 250 mg three times a day, in an open, randomized, comparative, clinical trial for the treatment of acute, uncomplicated, urinary tract infection. One hundred and two adult patients were eligible for safety evaluation; four patients were excluded due to side-effects (abdominal discomfort, nausea and vomiting). Ninety-eight patients were eligible for evaluation of efficacy. Clinical and bacteriological responses were comparable for both antibiotics. Leucopenia, nausea, and vaginal yeast infections were slightly more common in the cefprozil group. Cefprozil, 500 mg once daily, appears to be an appropriate alternative for the treatment of acute, uncomplicated urinary tract infections.

Development and impact of a computerized pediatric antiinfective decision support program.

OBJECTIVE: Computerized medical decision support tools have been shown to improve the quality of care and have been cited by the Institute of Medicine as one method to reduce pharmaceutical errors. We evaluated the impact of an antiinfective decision support tool in a pediatric intensive care unit (PICU). METHODS: We enhanced an existing adult antiinfective management tool by adding and changing medical logic to make it appropriate for pediatric patients. Process and outcomes measures were monitored prospectively during a 6-month control and a 6-month intervention period. Mandatory use of the decision support tool was initiated for all antiinfective orders in a 26-bed PICU during the intervention period. Clinician opinions of the decision support tool were surveyed via questionnaire. RESULTS: The rate of pharmacy interventions for erroneous drug doses declined by 59%. The rate of anti-infective subtherapeutic patient days decreased by 36%, and the rate of excessive-dose days declined by 28%. The number of orders placed per antiinfective course decreased 11.5%, and the robust estimate of the antiinfective costs per patient decreased 9%. The type of anti-infectives ordered and the number of antiinfective doses per patient remained similar, as did the rates of adverse drug events and antibiotic-bacterial susceptibility mismatches. The surveyed clinicians reported that use of the program improved their antiinfective agent choices as well as their awareness of impairments in renal function and reduced the likelihood of adverse drug events. CONCLUSIONS: Use of the pediatric antiinfective decision support tool in a PICU was considered beneficial to patient care by the clinicians and reduced the rates of erroneous drug orders, improved therapeutic dosage targets, and was associated with a decreased robust estimate of antiinfective costs per patient. antiinfective agents, decision support systems, drug therapy, medication errors, child, infant.

Synergistic action of amphotericin B and rifampin against Rhizopus species.

A 16-year-old diabetic patient developed Rhizopus pneumonia and was initially treated with amphotericin B for 7 days. Because of clinical deterioration of the patient, rifampin was added empirically. The patient improved clinically, and lung tissue removed surgically 8 weeks later showed no fungal elements by histopathological studies or by culture. An in vitro study of amphotericin B alone and in combination with rifampin against the isolate from the patient and 11 additional isolates of Rhizopus spp. was designed. The activity of amphotericin B in the presence of rifampin (10 or 5 micrograms/ml) increased fourfold against 9 of 10 clinical and 1 of 2 environmental isolates. Amphotericin B activity in the presence of 2 micrograms of rifampin per ml increased fourfold against 6 of 10 clinical isolates and increased twofold against an additional 3 clinical isolates. Amphotericin B in the presence of 1 microgram of rifampin per ml inhibited 9 of 10 isolates at a concentration of one-half the MIC of amphotericin B alone. These findings were confirmed by dose-response curves calculated from fungal dry weight determinations of Rhizopus spp. incubated in serial dilutions of amphotericin B combined with rifampin. These observations demonstrate in vitro, and possibly in vivo, synergy between amphotericin B and rifampin against Rhizopus spp.

Recovery of Pseudomonas gladioli from respiratory tract specimens of patients with cystic fibrosis.

Pseudomonas gladioli was isolated from 11 patients with cystic fibrosis. It resembled Pseudomonas cepacia on the selective and differential medium OFPBL, producing yellow colonies after 48 to 72 h of incubation. Isolates were characterized biochemically, by DNA hybridization, and by cellular fatty acid analysis. A review of the clinical status of selected patients colonized by P. gladioli did not reveal any apparent association of this organism with infectious complications of cystic fibrosis. Thus, the clinical implications may differ depending on which of these two closely related species is reported by laboratories. Determination of the fatty acid profile of isolates by gas chromatography may be a useful adjunct to biochemical characterization as a means of identification. In contrast to P. cepacia, most isolates of P. gladioli contained 3-OH C10:0 fatty acid under the growth conditions used.