SHEA NICU white paper series: Practical approaches for the prevention of viral respiratory infections.

This white paper provides clinicians and hospital leaders with practical guidance on the prevention and control of viral respiratory infections in the neonatal intensive care unit (NICU). This document serves as a companion to Centers for Disease Control and Prevention Healthcare Infection Control Practices Advisory Committee (HICPAC)'s "Prophylaxis and Screening for Prevention of Viral Respiratory Infections in Neonatal Intensive Care Unit Patients: A Systematic Review." It provides practical, expert opinion and/or evidence-based answers to frequently asked questions about viral respiratory detection and prevention in the NICU. It was developed by a writing panel of pediatric and pathogen-specific experts who collaborated with members of the HICPAC systematic review writing panel and the SHEA Pediatric Leadership Council to identify questions that should be addressed. The document has been endorsed by SHEA, the American Hospital Association (AHA), The Joint Commission, the Pediatric Infectious Diseases Society (PIDS), the Association for Professionals in Infection Control and Epidemiology (APIC), the Infectious Diseases Society of America (IDSA), and the National Association of Neonatal Nurses (NANN).

Petting Zoos as an Unsuspected Source of Pediatric Infections.

Children are at risk for infection following animal exposure at petting zoos owing to suboptimal hand hygiene and frequent hand-to-mucosal surface contact. Public health surveillance is limited, and infectious risk is likely underrecognized. Most reported infections are enteric. Here, we describe two children with unusual, nonenteric infections following petting zoo exposure.

The Use of Biomarkers in the Early Diagnosis of Septic Arthritis and Osteomyelitis-A Pilot Study.

BACKGROUND: The diagnosis of septic arthritis (SA) and osteomyelitis (OM) has remained challenging in the pediatric population, often accompanied by delays and requiring invasive interventions. The purpose of this pilot study is to identify a novel panel of biomarkers and cytokines that can accurately differentiate SA and OM at initial presentation using serum alone. METHODS: Twenty patients below 18 years old whose working diagnosis included SA (n=10) and OM (n=10) were identified. Serum was collected at initial evaluation. Each sample underwent seven ELISA [C1-C2, COMP, CS-846, hyaluronan, procalcitonin, PIIANP, C-terminal telopeptide of type II collagen (CTX-II)] and 65-plex cytokine panels. Principal component and Lasso regression analysis were performed to identify a limited set of predictive biomarkers. RESULTS: Mean age was 4.7 and 9.5 years in SA and OM patients, respectively (P=0.029). 50% of SA patients presented within 24 hours of symptom onset, compared with 0% of OM patients (P=0.033). 30% of SA patients were discharged home with an incorrect diagnosis and re-presented to the emergency department days later. At time of presentation: temperature ≥38.5°C was present in 10% of SA and 40% of OM patients (P=0.12), mean erythrocyte sedimentation rate (mm/h) was 51.6 in SA and 44.9 in OM patients (P=0.63), mean C-reactive protein (mg/dL) was 55.8 in SA and 71.8 in OM patients (P=0.53), and mean white blood cells (K/mm3) was 12.5 in SA and 10.4 in OM patients (P=0.34). 90% of SA patients presented with ≤2 of the Kocher criteria. 100% of SA and 40% of OM patients underwent surgery. 70% of SA cultures were culture negative, 10% MSSA, 10% Kingella, and 10% Strep pyogenes. 40% of OM cultures were culture negative, 50% MSSA, and 10% MRSA. Four biomarkers [CTx-II, transforming growth factor alpha (TGF-α), monocyte chemoattractant protein 1 (MCP-1), B cell-attracting chemokine 1] were identified that were able to classify and differentiate 18 of the 20 SA and OM cases correctly, with 90% sensitivity and 80% specificity. CONCLUSIONS: This pilot study identifies a panel of biomarkers that can differentiate between SA and OM at initial presentation using serum alone. LEVEL OF EVIDENCE: Level II-diagnostic study.

Infection Prevention during the Coronavirus Disease 2019 Pandemic.

COVID-19 is a nonspecific viral illness caused by a novel coronavirus, SARS-CoV-2, and led to an ongoing global pandemic. Transmission is primarily human-to-human via contact with respiratory particles containing infectious virus. The risk of transmission to health care personnel is low with proper use of personal protective equipment, including gowns, gloves, N95 or surgical mask, and eye protection. Additional measures affecting the risk of transmission include physical distancing, hand hygiene, routine cleaning and disinfection, appropriate air handling and ventilation, and public health interventions such as universal masking and stay-at-home orders.

Clostridioides difficile Infections in Inpatient Pediatric Oncology Patients: A Cohort Study Evaluating Risk Factors and Associated Outcomes.

BACKGROUND: Clostridioides difficile infection (CDI) is a significant source of morbidity in pediatric cancer patients. Few reports to date have evaluated risk factors and short-term outcomes for this population. METHODS: We retrospectively evaluated pediatric oncology admissions at St Louis Children's Hospital from 2009 to 2018. All inpatient cases of diagnosed initial CDI were identified. We aimed to investigate the prevalence of CDI and associated risk factors, including coadmission with another patient with CDI, and to evaluate short-term outcomes including length of stay and delays in subsequent scheduled chemotherapy. RESULTS: Review of 6567 admissions from 952 patients revealed 109 CDI cases (11.4% of patients). Patients with leukemia or lymphoma, compared to those with solid tumors, were more likely to have CDI (odds ratio [OR], 3 [95% CI, 1.4-6.6], and 3 [95% CI, 1.3-6.8], respectively). Autologous hematopoietic stem cell transplant (HSCT) was also a risk factor (OR, 3.5 [95% CI, 1.7-7.4]). Prior antibiotic exposure independently increased the risk for CDI (OR, 3.0 [95% CI, 1.8-4.8]). Concurrent admission with another patient with CDI also significantly increased the risk (OR, 84.7 [95% CI, 10.5-681.8]). In contrast to previous reports, exposure to acid-suppressing medications decreased the risk for CDI (OR, 0.5 [95% CI, .3-.7]). CDI was associated with increased length of stay (mean difference, 8 days [95% CI, 4.6-11.4]) and prolonged delays for subsequent chemotherapy (mean difference, 1.4 days [95% CI, .1-2.7]). CONCLUSIONS: CDI in pediatric oncology patients significantly prolongs hospitalization and delays chemotherapy treatment plans. Interventions to control CDI will improve the care of pediatric oncology patients.

Delayed Development of Coronary Artery Dilitation in Suspected Severe Acute Respiratory Syndrome Coronavirus 2 Multisystem Inflammatory Syndrome: More Research Needed.

Although significant disease burden in the severe acute respiratory syndrome coronavirus 2 pandemic has been relatively uncommon in children, worldwide cases of a postinfectious multisystem inflammatory syndrome in children and possible atypical Kawasaki-like disease attributing to severe acute respiratory syndrome coronavirus 2 infection have arisen. Original thinking for coronavirus disease-19 disease was that an overwhelming proinflammatory response drove disease pathogenesis. Emerging reports suggest that a robust immune suppression may be more relevant and predominant. Recently reported data on children with multisystem inflammatory syndrome in children have demonstrated a heterogeneity of immune phenotypes among these patients, with concern for a strong initial proinflammatory state; however, data are lacking to support this. Likewise, understanding development of certain clinical findings to changes in the immune system is lacking. CASE SUMMARY: We report a 12-year-old multiracial male with negative coronavirus disease-19 nasopharyngeal RNA polymerase chain reaction testing but positive severe acute respiratory syndrome coronavirus 2 serology, subsequent development of vasodilatory shock with myocardial depression, and subsequent delayed development of coronary artery dilatation after resolution of myocardial depression. Unlike previous reported cases of multisystem inflammatory syndrome in children, he exhibited profound lymphopenia without specific inflammatory cytokines elevations, whereas nonspecific markers (ferritin and C-reactive protein) were increased. He subsequently was discharged on day 12 of hospitalization with complete recovery. CONCLUSION: Our representative case of a patient with coronavirus disease-19-associated multisystem inflammatory syndrome in children without robust hyperinflammation and a delayed finding of coronary artery dilatation compared with reported case series highlights the need for further mechanistic understanding of coronavirus disease-19 disease and subsequent multisystem inflammatory syndrome in children or Kawasaki disease development. This report offers a number of disease mechanisms and clinical evolution considerations for further elucidation to guide development of potential therapies.

Ureaplasma urealyticum pyelonephritis presenting with progressive dysuria, renal failure, and neurologic symptoms in an immunocompromised patient.

Ureaplasma urealyticum is a bacterial species correlated with urethritis in healthy individuals and invasive infections in immunocompromised patients. We describe a 20-year-old female with a history of remote heart transplant on everolimus, mycophenolate, and rituximab presenting with progressive urinary tract symptoms, renal failure, and neurologic symptoms. An extensive workup ultimately identified U urealyticum infection, and the patient successfully recovered after a course of azithromycin and doxycycline.

Posaconazole-induced hypertension and hypokalemia due to inhibition of the 11ß-hydroxylase enzyme.

Posaconazole is an antifungal therapy reported to cause incident hypertension. Hypokalemia is also a known side effect. The combination of hypertension and hypokalemia suggests mineralocorticoid excess. We present the case of a 15-year-old adolescent male with hypertensive urgency while on prophylactic posaconazole therapy for a combined immunodeficiency. We identify the mechanism of posaconazole-induced hypertension to be inhibition of the 11ß-hydroxylase enzyme, resulting in elevated levels of the mineralocorticoid receptor activator deoxycorticosterone. Loss of function of the 11ß-hydroxylase enzyme is responsible for a rare form of congenital adrenal hyperplasia and can be associated with life-threatening adrenal crisis.

Vancomycin Concentrations in Paraspinal Muscles During Posterior Spinal Fusions for Neuromuscular Scoliosis.

STUDY DESIGN: Prospective consecutively enrolled cohort. OBJECTIVES: To evaluate paraspinal muscle concentration of intravenously administered vancomycin, at predetermined time points, during posterior spinal fusion (PSF) with instrumentation in neuromuscular scoliosis (NMS). SUMMARY: Surgical site infection (SSI) after PSF for NMS can be a devastating complication, which may lead to prolonged antibiotic use, multiple additional surgical procedures, pseudarthroses, and sepsis. Because of significant morbidity of SSIs in NMS, the prophylactic use of vancomycin has been adopted at our institution as standard wound prophylaxis, despite any high-level evidence of its efficacy. METHODS: A prospective study of 20 patients who underwent definitive PSF for NMS and received vancomycin infusion preoperatively per institutional protocol. Serum levels were obtained immediately after infusion, at surgical incision, and then at 1, 2, and 4 hours post incision. Muscle tissue samples were simultaneously obtained at incision and at 1, 2, and 4 hours post incision. Samples were analyzed by a validated liquid chromatography-tandem mass spectrometry method. RESULTS: 10 males and 10 females with a mean age of 14+11 years (9-20 years) received a mean infusion of 15.0 mg/kg vancomycin. Mean serum levels were 26.7 µg/mL after infusion, 18.1 at incision, 13.2 at 1 hour, 11.8 at 2 hours, and 7.6 at 4 hours post infusion. Mean muscle levels were 0.5 µg/mL at incision, 0.6 at 1 hour, 0.5 at 2 hours, and 0.7 at 4 hours post infusion. Mean serum levels reached minimum inhibitory concentration (MIC) for Staphylococcus aureus at incision and at all timepoints during surgery. Mean muscle vancomycin levels never reached MIC. No patients had any cardiac or kidney disease, and all patients had normal kidney function according to their preoperative laboratory values. CONCLUSIONS: Using accepted guidelines for the administration of intravenous vancomycin preoperatively, serum levels reached MIC at incision and at all timepoints tested during PSF for neuromuscular scoliosis. At no timepoint tested did muscle levels reach MIC. LEVEL OF EVIDENCE: Level II.

Bacterial Infections in Neonates Following Mupirocin-Based MRSA Decolonization: A Multicenter Cohort Study.

OBJECTIVE To characterize the risk of infection after MRSA decolonization with intranasal mupirocin. DESIGN Multicenter, retrospective cohort study. SETTING Tertiary care neonatal intensive care units (NICUs) from 3 urban hospitals in the United States ranging in size from 45 to 100 beds. METHODS MRSA-colonized neonates were identified from NICU admissions occurring from January 2007 to December 2014, during which a targeted decolonization strategy was used for MRSA control. In 2 time-to-event analyses, MRSA-colonized neonates were observed from the date of the first MRSA-positive surveillance screen until (1) the first occurrence of novel gram-positive cocci in sterile culture or discharge or (2) the first occurrence of novel gram-negative bacilli in sterile culture or discharge. Mupirocin exposure was treated as time varying. RESULTS A total of 522 MRSA-colonized neonates were identified from 16,144 neonates admitted to site NICUs. Of the MRSA-colonized neonates, 384 (74%) received mupirocin. Average time from positive culture to mupirocin treatment was 3.5 days (standard deviation, 7.2 days). The adjusted hazard of gram-positive cocci infection was 64% lower among mupirocin-exposed versus mupirocin-unexposed neonates (hazard ratio, 0.36; 95% confidence interval [CI], 0.17-0.76), whereas the adjusted hazard ratio of gram-negative bacilli infection comparing mupirocin-exposed and -unexposed neonates was 1.05 (95% CI, 0.42-2.62). CONCLUSIONS In this multicentered cohort of MRSA-colonized neonates, mupirocin-based decolonization treatment appeared to decrease the risk of infection with select gram-positive organisms as intended, and the treatment was not significantly associated with risk of subsequent infections with organisms not covered by mupirocin's spectrum of activity. Infect Control Hosp Epidemiol 2017;38:930-936.

Antibiotic Prophylaxis Is Associated with Subsequent Resistant Infections in Children with an Initial Extended-Spectrum-Cephalosporin-Resistant Enterobacteriaceae Infection.

The objective of this study was to assess the association between previous antibiotic use, particularly long-term prophylaxis, and the occurrence of subsequent resistant infections in children with index infections due to extended-spectrum-cephalosporin-resistant Enterobacteriaceae We also investigated the concordance of the index and subsequent isolates. Extended-spectrum-cephalosporin-resistant Escherichia coli and Klebsiella spp. isolated from normally sterile sites of patients aged <22 years were collected along with associated clinical data from four freestanding pediatric centers. Subsequent isolates were categorized as concordant if the species, resistance determinants, and fumC-fimH (E. coli) or tonB (Klebsiella pneumoniae) type were identical to those of the index isolate. In total, 323 patients had 396 resistant isolates; 45 (14%) patients had ≥1 subsequent resistant infection, totaling 73 subsequent resistant isolates. The median time between the index and first subsequent infections was 123 (interquartile range, 43 to 225) days. In multivariable Cox proportional hazards analyses, patients were 2.07 times as likely to have a subsequent resistant infection (95% confidence interval, 1.11 to 3.87) if they received prophylaxis in the 30 days prior to the index infection. In 26 (58%) patients, all subsequent isolates were concordant with their index isolate, and 7 (16%) additional patients had at least 1 concordant subsequent isolate. In 12 of 17 (71%) patients with E. coli sequence type 131 (ST131)-associated type 40-30, all subsequent isolates were concordant. Subsequent extended-spectrum-cephalosporin-resistant infections are relatively frequent and are most commonly due to bacterial strains concordant with the index isolate. Further study is needed to assess the role prophylaxis plays in these resistant infections.

The Molecular and Clinical Epidemiology of Extended-Spectrum Cephalosporin- and Carbapenem-Resistant Enterobacteriaceae at 4 US Pediatric Hospitals.

OBJECTIVE: In this report, we aim to describe the epidemiology of extended-spectrum cephalosporin-resistant (ESC-R) and carbapenem-resistant (CR) Enterobacteriaceae infections in children. METHODS: ESC-R and CR Enterobacteriaceae isolates from normally sterile sites of patients aged <22 years from 4 freestanding pediatric medical centers were collected along with the associated clinical data. RESULTS: The overall frequencies of ESC-R and CR isolates according to hospital over the 4-year study period ranged from 0.7% to 2.8%. Rates of ESC-R or CR Escherichia coli and Klebsiella pneumoniae varied according to hospital and ranged from 0.75 to 3.41 resistant isolates per 100 isolates (P < .001 for any differences). E coli accounted for 272 (77%) of the resistant isolates; however, a higher rate of resistance was observed in K pneumoniae isolates (1.78 vs 1.27 resistant isolates per 100 same-species isolates, respectively; P = .005). One-third of the infections caused by ESC-R or CR E coli were community-associated. In contrast, infections caused by ESC-R or CR K pneumoniae were more likely than those caused by resistant E coli to be healthcare- or hospital-associated and to occur in patients with an indwelling device (P ≤ .003 for any differences, multivariable logistic regression). Nonsusceptibility to 3 common non-ß-lactam agents (ciprofloxacin, gentamicin, and trimethoprim-sulfamethoxazole) occurred in 23% of the ESC-R isolates. The sequence type 131-associated fumC/fimH-type 40-30 was the most prevalent sequence type among all resistant E coli isolates (30%), and the clonal group 258-associated allele tonB79 was the most prevalent allele among all resistant K pneumoniae isolates (10%). CONCLUSIONS: The epidemiology of ESC-R and CR Enterobacteriaceae varied according to hospital and species (E coli vs K pneumoniae). Both community and hospital settings should be considered in future research addressing pediatric ESC-R Enterobacteriaceae infection.

Previous Antibiotic Exposure Increases Risk of Infection with Extended-Spectrum-ß-Lactamase- and AmpC-Producing Escherichia coli and Klebsiella pneumoniae in Pediatric Patients.

The objective of this study was to determine whether antibiotic exposure is associated with extended-spectrum-beta-lactamase- or AmpC-producing Escherichia coli or Klebsiella pneumoniae infections in children. We collected extended-spectrum-beta-lactamase- or AmpC-producing E. coli or K. pneumoniae isolates and same-species susceptible controls from normally sterile sites of patients aged ≤21 years, along with associated clinical data, at four free-standing pediatric centers. After controlling for potential confounders, the relative risk of having an extended-spectrum-beta-lactamase-producing isolate rather than a susceptible isolate was 2.2 times higher (95% confidence interval [CI], 1.49 to 3.35) among those with antibiotic exposure in the 30 days prior to infection than in those with no antibiotic exposure. The results were similar when analyses were limited to exposure to third-generation cephalosporins, other broad-spectrum beta-lactams, or trimethoprim-sulfamethoxazole. Conversely, the relative risk of having an AmpC-producing versus a susceptible isolate was not significantly elevated with any antibiotic exposure in the 30 days prior to infection (adjusted relative risk ratio, 1.12; 95% CI, 0.65 to 1.91). However, when examining subgroups of antibiotics, the relative risk of having an AmpC-producing isolate was higher for patients with exposure to third-generation cephalosporins (adjusted relative risk ratio, 4.48; 95% CI, 1.75 to 11.43). Dose-response relationships between antibiotic exposure and extended-spectrum-beta-lactamase-producing or AmpC-producing isolates were not demonstrated. These results reinforce the need to study and implement pediatric antimicrobial stewardship strategies, and they indicate that epidemiological studies of third-generation cephalosporin-resistant E. coli and K. pneumoniae isolates should include resistance mechanisms when possible.

Metagenomic Approach for Identification of the Pathogens Associated with Diarrhea in Stool Specimens.

The potential to rapidly capture the entire microbial community structure and/or gene content makes metagenomic sequencing an attractive tool for pathogen identification and the detection of resistance/virulence genes in clinical settings. Here, we assessed the consistency between PCR from a diagnostic laboratory, quantitative PCR (qPCR) from a research laboratory, 16S rRNA gene sequencing, and metagenomic shotgun sequencing (MSS) for Clostridium difficile identification in diarrhea stool samples. Twenty-two C. difficile-positive diarrhea samples identified by PCR and qPCR and five C. difficile-negative diarrhea controls were studied. C. difficile was detected in 90.9% of C. difficile-positive samples using 16S rRNA gene sequencing, and C. difficile was detected in 86.3% of C. difficile-positive samples using MSS. CFU inferred from qPCR analysis were positively correlated with the relative abundance of C. difficile from 16S rRNA gene sequencing (r(2) = -0.60) and MSS (r(2) = -0.55). C. difficile was codetected with Clostridium perfringens, norovirus, sapovirus, parechovirus, and anellovirus in 3.7% to 27.3% of the samples. A high load of Candida spp. was found in a symptomatic control sample in which no causative agents for diarrhea were identified in routine clinical testing. Beta-lactamase and tetracycline resistance genes were the most prevalent (25.9%) antibiotic resistance genes in these samples. In summary, the proof-of-concept study demonstrated that next-generation sequencing (NGS) in pathogen detection is moderately correlated with laboratory testing and is advantageous in detecting pathogens without a priori knowledge.

Risk Factors for Craniotomy or Spinal Fusion Surgical Site Infection.

BACKGROUND: Surgical site infections (SSIs) occur in approximately 700 pediatric patients annually and are associated with increased morbidity, mortality and cost. The aim of this study is to determine risk factors for SSI among pediatric patients undergoing craniotomy and spinal fusion. METHODS: This is a retrospective case-control study. Cases were craniotomy or spinal fusion patients with SSI as defined by Centers for Disease Control and Prevention criteria with surgery performed from January 1, 2008 to July 31, 2009. For each case patient, 3 uninfected controls were randomly selected among patients who underwent the same procedure as the case patient within 1 month. We performed analyses of risk factors for craniotomy and spinal fusion SSI separately and as a combined outcome variable. RESULTS: Underweight body mass index, increased time at lowest body temperature, increased interval to antibiotic redosing, the combination of vancomycin and cefazolin for prophylaxis, longer preoperative and postoperative intensive care unit stay and anticoagulant use at 2 weeks postoperatively were associated with an increased risk of SSI in the combined analysis of craniotomy and spinal fusion. Forty-seven percent of cases and 27% of controls received preoperative antibiotic doses that were inappropriately low because of their weight. CONCLUSIONS: We identified modifiable risk factors for SSI including antibiotic dosing and body temperature during surgery. Preoperative antibiotic administration is likely to benefit from standard processes. Further studies of risk benefit for prolonged low body temperature during procedures are needed to determine the optimal balance between neuroprotection and potential immunosuppression associated with low body temperature.

Successful Use of Temocillin as Salvage Therapy for Cervical Osteomyelitis Secondary to Multidrug-Resistant Burkholderia cepacia.

Infection with multidrug resistant Burkholderia cepacia presents a therapeutic challenge in patients with cystic fibrosis. In this study, we present a case of progressive cervical osteomyelitis secondary to B cepacia that failed surgical drainage and extended therapy with meropenem, piperacillin-tazobactam, doxycycline, and aminoglycosides. Temocillin (Negaban) was successfully used to clear the infection.

Daily chlorhexidine bathing to reduce bacteraemia in critically ill children: a multicentre, cluster-randomised, crossover trial.

BACKGROUND: Bacteraemia is an important cause of morbidity and mortality in critically ill children. Our objective was to assess whether daily bathing in chlorhexidine gluconate (CHG) compared with standard bathing practices would reduce bacteraemia in critically ill children. METHODS: In an unmasked, cluster-randomised, two-period crossover trial, ten paediatric intensive-care units at five hospitals in the USA were randomly assigned a daily bathing routine for admitted patients older than 2 months, either standard bathing practices or using a cloth impregnated with 2% CHG, for a 6-month period. Units switched to the alternative bathing method for a second 6-month period. 6482 admissions were screened for eligibility. The primary outcome was an episode of bacteraemia. We did intention-to-treat (ITT) and per-protocol (PP) analyses. This study is registered with ClinicalTrials.gov (identifier NCT00549393). FINDINGS: 1521 admitted patients were excluded because their length of stay was less than 2 days, and 14 refused to participate. 4947 admissions were eligible for analysis. In the ITT population, a non-significant reduction in incidence of bacteraemia was noted with CHG bathing (3·52 per 1000 days, 95% CI 2·64-4·61) compared with standard practices (4·93 per 1000 days, 3·91-6·15; adjusted incidence rate ratio [aIRR] 0·71, 95% CI 0·42-1·20). In the PP population, incidence of bacteraemia was lower in patients receiving CHG bathing (3·28 per 1000 days, 2·27-4·58) compared with standard practices (4·93 per 1000 days, 3·91-6·15; aIRR 0·64, 0·42-0·98). No serious study-related adverse events were recorded, and the incidence of CHG-associated skin reactions was 1·2 per 1000 days (95% CI 0·60-2·02). INTERPRETATION: Critically ill children receiving daily CHG bathing had a lower incidence of bacteraemia compared with those receiving a standard bathing routine. Furthermore, the treatment was well tolerated. FUNDING: Sage Products, US National Institutes of Health.

Use of Administrative Data for the Identificationof Laboratory-Confirmed Influenza Infection: The Validity ofInfluenza-Specific ICD-9 Codes.

We used Pediatric Health Information System data and laboratory records from 3 children's hospitals to determine whether administrative data accurately identify children with laboratory-confirmed influenza. Among 23 282 inpatients, diagnosis codes for influenza detected 73% of laboratory-confirmed influenza cases, whereas <1% of patients without a diagnosis code had laboratory-confirmed influenza.

Oseltamivir dosing in premature infants.

We conducted a 2-sample pharmacokinetic study of oseltamivir in 12 premature infants. Oseltamivir 1 mg/kg/dose twice daily in infants <38 weeks postmenstrual age (n=8) resulted in oseltamivir carboxylate exposure comparable to previously published pediatric data, which helps prospectively validate this regimen. Oseltamivir 3 mg/kg/dose once daily in premature infants >38 weeks postmenstrual age (born prematurely but chronologically past term, n=4) resulted in similar oseltamivir and oseltamivir carboxylate exposure. Although these results suggest persistence of immature renal function in this subgroup, further pharmacokinetic/pharmacodynamic description is required to confirm the appropriateness of this regimen.