Use of antimicrobial agents in United States neonatal and pediatric intensive care patients.

OBJECTIVE: Antimicrobial use contributes to the development of emergence and dissemination of antimicrobial-resistant bacteria among intensive care unit (ICU) patients. There are few published data on antimicrobial use in neonatal (NICU) and pediatric ICU (PICU) patients. METHODS: Personnel at 31 Pediatric Prevention Network hospitals participated in point prevalence surveys on August 4, 1999 (summer) and February 8, 2000 (winter). Data collected for all NICU and PICU inpatients included demographics, antimicrobials and indications for use and therapeutic interventions. RESULTS: Data were reported for 2647 patients in 29 NICUs (827 patients in summer; 753 in winter) and 35 PICUs (512 patients in summer; 555 in winter). PICU patients were more likely than NICU patients to be receiving antimicrobials on the survey date [758 of 1070 (70.8%) versus 684 of 1582 (43.2%), P < 0.0001]. NICU patients were receiving a higher median number of antimicrobials (2 versus 1, P < 0.0001). The most common agents among NICU patients were gentamicin, ampicillin and vancomycin; the most common agents among PICU patients were cefazolin, vancomycin and cefotaxime. Use of aminoglycosides, aminopenicillins and topical antibacterials was significantly more common in NICU patients; first, second and third generation cephalosporins, extended spectrum penicillins, sulfonamides, fluoroquinolones, antianaerobic agents, systemic antifungals and systemic antivirals were more common in PICU patients. CONCLUSIONS: This is the first U.S. national multicenter description of antimicrobial use in NICUs and PICUs and demonstrates the high prevalence of antimicrobial use among these patients. Assessment strategies targeting antimicrobial use in pediatrics are needed.

Improving influenza immunization rates among healthcare workers caring for high-risk pediatric patients.

OBJECTIVE: To assess influenza vaccination rates of healthcare workers (HCWs) in neonatal intensive care units (NICUs), pediatric intensive care units (PICUs), and oncology units in Pediatric Prevention Network (PPN) hospitals. PARTICIPANTS: Infection control practitioners and HCWs in NICUs, PICUs, and oncology units. METHODS: In November 2000, posters, electronic copies of a slide presentation, and an influenza fact sheet were distributed to 32 of 76 PPN hospitals. In January 2001, a survey was distributed to PPN hospital participants to obtain information about the immunization campaigns. On February 7, 2001, a survey of influenza immunization was conducted among HCWs in NICU, PICU, and oncology units at participating hospitals. RESULTS: Infection control practitioners from 19 (25%) of the 76 PPN hospitals completed the surveys. The median influenza immunization rate was 43% (range, 12% to 63%), with 7 hospitals exceeding 50%. HCWs (n = 1123) at 15 PPN hospitals completed a survey; 53% of HCWs reported receiving influenza immunization. Immunization rates varied by work site: 52% in NICUs and PICUs compared with 60% in oncology units. Mobile carts and PPN educational fact cards were associated with higher rates among these subpopulations (P < .001) (361 [63%] of 575 vs 236 [44%] of 541 for mobile carts; 378 [60%] of 633 vs 219 [45%] of 483 for fact cards). CONCLUSION: Despite delayed distribution of influenza vaccine during the 2000-2001 season, immunization rates at 7 hospitals and among HCWs in high-risk units exceeded the National Association of Children's Hospitals and Related Institutions goal of 50%.

Equivalence of ELISpot assays demonstrated between major HIV network laboratories.

BACKGROUND: The Comprehensive T Cell Vaccine Immune Monitoring Consortium (CTC-VIMC) was created to provide standardized immunogenicity monitoring services for HIV vaccine trials. The ex vivo interferon-gamma (IFN-γ) ELISpot is used extensively as a primary immunogenicity assay to assess T cell-based vaccine candidates in trials for infectious diseases and cancer. Two independent, GCLP-accredited central laboratories of CTC-VIMC routinely use their own standard operating procedures (SOPs) for ELISpot within two major networks of HIV vaccine trials. Studies are imperatively needed to assess the comparability of ELISpot measurements across laboratories to benefit optimal advancement of vaccine candidates. METHODS: We describe an equivalence study of the two independently qualified IFN-g ELISpot SOPs. The study design, data collection and subsequent analysis were managed by independent statisticians to avoid subjectivity. The equivalence of both response rates and positivity calls to a given stimulus was assessed based on pre-specified acceptance criteria derived from a separate pilot study. FINDINGS: Detection of positive responses was found to be equivalent between both laboratories. The 95% C.I. on the difference in response rates, for CMV (-1.5%, 1.5%) and CEF (-0.4%, 7.8%) responses, were both contained in the pre-specified equivalence margin of interval [-15%, 15%]. The lower bound of the 95% C.I. on the proportion of concordant positivity calls for CMV (97.2%) and CEF (89.5%) were both greater than the pre-specified margin of 70%. A third CTC-VIMC central laboratory already using one of the two SOPs also showed comparability when tested in a smaller sub-study. INTERPRETATION: The described study procedure provides a prototypical example for the comparison of bioanalytical methods in HIV vaccine and other disease fields. This study also provides valuable and unprecedented information for future vaccine candidate evaluations on the comparison and pooling of ELISpot results generated by the CTC-VIMC central core laboratories.

Vancomycin use in hospitalized pediatric patients.

OBJECTIVES: To assess vancomycin utilization at children's hospitals, to determine risk factors for vancomycin use and length of therapy, and to facilitate adapting recommendations to optimize vancomycin prescribing practices in pediatric patients. METHODS: Two surveys were conducted at Pediatric Prevention Network hospitals. The first (Survey I) evaluated vancomycin control programs. The second (Survey II) prospectively reviewed individual patient records. Each hospital was asked to complete questionnaires on 25 consecutive patients or all patients for whom vancomycin was prescribed during a 1-month period. RESULTS: In Survey I, 55 of 65 (85%) hospitals reported their vancomycin control policies. Three quarters had specific policies in place to restrict vancomycin use. One half had at least 3 vancomycin restriction measures. In Survey II, personnel at 22 hospitals reviewed 416 vancomycin courses, with 2 to 25 (median = 12) patients tracked per hospital. Eighty-two percent of the vancomycin prescribed was for treatment of neonatal sepsis, fever/neutropenia, fever of unknown origin, positive blood culture, pneumonia, or meningitis. In an additional 6% (26/416), vancomycin was prescribed for patients with beta-lactam allergies and in 13% (56/416) for prophylaxis. Median duration of prophylaxis was 2 days (range: 1-15 days). Almost half (196, 47%) of the patients who received vancomycin were in intensive care units; 27% of the vancomycin courses were initiated by neonatologists and 19% by hematologists/oncologists. The predominant risk factor at the time of vancomycin initiation was the presence of vascular catheters (322, 77%); other host factors included cancer chemotherapy (55, 13%), transplant (30, 7%), shock (24, 6%), other immunosuppressant therapy (17, 4%), or hyposplenic state (2, <1%). Other clinical considerations were severity of illness (96, 23%), uncertainty about diagnosis (51, 12%), patient not responding to current antibiotic therapy (40, 10%), or implant infection (13, 3%). When vancomycin was initiated, blood cultures were positive in 85 patients (20%); cultures from other sites were positive in 45 (11%), and Gram stains of body fluids were positive in 37 (9%). In 29 (7%) patients, organisms sensitive only to vancomycin were isolated before vancomycin initiation. Reasons for discontinuing vancomycin included: therapeutic course completed (125, 30%), negative cultures (106, 25%), alternative antibiotics initiated (75, 18%), illness resolved (14, 3%), or patient expired (13, 3%). Final results of blood culture isolates resistant to beta-lactam antibiotics included 48 coagulase-negative staphylococcus, 5 Staphylococcus aureus, and 10 other species. CONCLUSIONS: At children's hospitals, vancomycin is initiated for therapy in patients who have vascular catheters and compromised host factors. Only 7% had laboratory-confirmed beta-lactam-resistant organisms isolated at the time vancomycin was prescribed. Efforts to modify empiric vancomycin use in children's hospitals should be targeted at intensivists, neonatologists, and hematologists. Initiatives to decrease length of therapy by decreasing the number of surgical prophylaxis doses and days of therapy before laboratory results may decrease vancomycin exposure.

A national point-prevalence survey of pediatric intensive care unit-acquired infections in the United States.

OBJECTIVE: To determine the prevalence of intensive care unit-acquired infections, a major cause of morbidity in pediatric intensive care unit (PICU) patients. METHODS: Pediatric Prevention Network hospitals (n = 31) participated in a point-prevalence survey on August 4, 1999. Data collected for all PICU inpatients included demographics, infections, therapeutic interventions, and outcomes. RESULTS: There were 512 patients in 35 PICUs. The median age was 2.2 years (range, <1 day-35.4 years). Seventy-five PICU-acquired infections occurred among 61 (11.9%) patients. The most frequently reported sites were bloodstream (31 [41.3%]), lower respiratory tract (17 [22.7%]), urinary tract (10 [13.3%]), or skin/soft tissue (6 [8.0%]). The most frequent pathogens were coagulase-negative staphylococci (in 16 [21.3%] infections), Candida spp. (13 [17.3%]), enterococci (10 [13.3%]), Staphylococcus aureus (9 [12.0%]), or Pseudomonas aeruginosa (8 [10.7%]). Age-adjusted risk factors for infection included central intravenous catheters (relative risk [RR], 4.1; 95% confidence intervals [CI], 2.4-7.1), arterial catheters (RR, 2.4; 95% CI, 1.5-3.9), total parenteral nutrition (RR, 5.5; 95% CI, 3.6-8.5), or mechanical ventilation (RR, 3.9; 95% CI, 2.2-6.8). Infection was associated with higher age-adjusted risk of death within 4 weeks of the survey (RR, 3.4; 95% CI, 1.7-6.5). CONCLUSIONS: This national multicenter study documented the high prevalence of PICU-acquired infections. Preventing these infections should be a national priority.