Comparison of Outcomes in Neonates Receiving Cefepime or Ceftazidime.

OBJECTIVES: Cefepime and ceftazidime are alternatives to cefotaxime for management of Gram-negative infections in neonates. The objective was to evaluate neonatal outcomes when receiving cefepime or ceftazidime. METHODS: This was a single center, retrospective analysis of neonates exposed to at least 24 hours of cefepime or ceftazidime between June 1, 2018, and June 1, 2021. The primary outcome was incidence of culture-positive, late-onset sepsis after initial exposure. Secondary outcomes included culture-negative, respiratory, urinary tract, and resistant infections; necrotizing enterocolitis; length of stay; age at discharge; mortality; and adverse effects. RESULTS: A total of 105 neonates were included (cefepime, n = 50; ceftazidime, n = 55). Baseline characteristics were similar except more cumulative days of antibiotics (25.0 [IQR, 9.3-47.0] versus 9.0 [IQR, 4.0-23.5], p = 0.01), central line days (11.0 [IQR, 6.0-40.0] versus 6.5 [IQR, 0.0-11.5], p = 0.001), and ventilator days (13.0 [IQR, 2.3-48.0] versus 4.0 [IQR, 0.0-25.0], p = 0.02) were found in the cefepime group than in the ceftazidime group. There was no difference in culture-positive sepsis after the initial antibiotic course (8.0% versus 3.6%, p = 0.42). Statistical differences were seen in select secondary outcomes including treated respiratory infections (16.0% versus 1.8%, p = 0.01), length of stay greater than 30 days (72.0% versus 50.9%, p = 0.03), and mortality (26.0% versus 9.1%, p = 0.02). These differences were not observed in analyses adjusted for ventilator days. CONCLUSIONS: This analysis found no difference in culture-positive sepsis in neonates exposed to cefepime versus ceftazidime. Moreover, there were no differences in secondary outcomes in adjusted analyses. Further research is needed to assess neonatal outcomes in a larger analysis.

Successful Eradication of a Highly Resistant Elizabethkingia anophelis Species in a Premature Neonate With Bacteremia and Meningitis.

Elizabethkingia anophelis is a Gram-negative bacillus that can exhibit highly resistant phenotypes against most antibiotics with evidence of efficacy and safety in the neonatal population. Given the limited antimicrobial options, clinicians may be forced into challenging treatment scenarios when faced with central nervous system infections in premature neonates caused by E. anophelis . We report a case of successful treatment of hospital-acquired meningitis and bacteremia caused by E. anophelis at 11 days of life in a male infant born at 29 weeks, 1 day gestation and birth weight of 1.41 kg. Therapy consisted of vancomycin, dose adjusted to maintain goal troughs of 15-20 mg/L, and rifampin 10 mg/kg/dose every 12 hours, with ciprofloxacin 15 mg/kg/dose every 12 hours and trimethoprim/sulfamethoxazole 5 mg/kg/dose every 12 hours added due to antimicrobial susceptibilities and unsatisfactory response, for a total of 21 days. Following initiation of this multidrug regimen, repeat cultures were negative, laboratory parameters improved [with exception of elevated cerebrospinal fluid (CSF) white blood cell count], the patient remained otherwise stable, and there were no adverse effects noted from therapy. Complications after treatment included the requirement of bilateral hearing aids and the development of hydrocephalus necessitating ventriculoperitoneal shunt placement. To our knowledge, we report the first case of meningitis in a premature neonate initially identified as E. anophelis in the United States treated with this regimen which led to successful microbiologic eradication with no antimicrobial safety concerns.

Implementation of a Standardized Premedication Bundle to Improve Procedure Success for Nonemergent Neonatal Intubations.

The American Academy of Pediatrics recommends premedication for all nonemergent neonatal intubations, yet there remains significant variation in this practice nationally. We aimed to standardize our unit's premedication practices for improved intubation success and reduced adverse events. Methods: The study workgroup developed educational material and protocol content. Process measures included premedication use, education, and audit form completion. Primary (success on first intubation attempt and adverse event rates) and secondary (trainee success) study outcomes are displayed using statistical process control charts and pre-post cohort comparisons. Results: Forty-seven percent (97/206) of nurses completed educational intervention before protocol release, with an additional 20% (42/206) following a staff reminder. Two hundred sixteen (216) patients were intubated per protocol with 81% (174/216) audit completion. Compared with baseline (n = 158), intubation attempts decreased from 2 (IQR, 1-2) to 1 (IQR, 1-2) (P = 0.03), and success on the first attempt increased from 40% (63/158) to 57% (124/216) (P < 0.01), with a notable improvement in trainee success from less than 1% (1/40) to 43% (31/72) (P < 0.01). The rate of severe and rare adverse events remained stable; however, there was a rise in nonsevere events from 30% (48/158) to 45% (98/216). The tachycardia rate increased with atropine use. There was no change in chest wall rigidity, number of infants unable to extubate following surfactant, or decompensation awaiting medications. Conclusions: Standardizing procedural care delivery reduced intubation attempts and increased the attempt success rate. However, this was accompanied by an increase in the rate of nonsevere adverse events.

Characterization of the Clinical Outcomes With Cefepime in a Neonatal Intensive Care Unit: A Retrospective Cohort Study.

OBJECTIVES: The objective of this study was to characterize clinical outcomes when cefepime was used in a neonatal intensive care population. METHODS: Data were extracted from the medical records of all full-term (40 weeks gestational age) patients up to 2 months of age and preterm patients up to 48 weeks postmenstrual age admitted to the neonatal intensive care unit (NICU) at a freestanding children's hospital between January 1, 2010, and December 31, 2013, who received at least 48 hours of cefepime. The primary outcome measure was a positive clinical response as defined by a normalization of white blood cell count and/or culture clearance. RESULTS: Final analysis included 74 patients. Clinical response was evaluable in 43.2% (32 of 74) of courses. Of these, positive clinical response was observed in 81.3% (26 of 32). Overall patient mortality was 16.2% (12 of 74). Adverse effects (AEs) occurred in 14.9% (11 of 74) of courses. CONCLUSIONS: Cefepime can be used safely with reasonable clinical response in a NICU population, but additional studies are needed to further determine cefepime-associated clinical outcomes.

Standardized Treatment of Neonatal Status Epilepticus Improves Outcome.

We aimed to decrease practice variation in treatment of neonatal status epilepticus by implementing a standardized protocol. Our primary goal was to achieve 80% adherence to the algorithm within 12 months. Secondary outcome measures included serum phenobarbital concentrations, number of patients progressing from seizures to status epilepticus, and length of hospital stay. Data collection occurred for 6 months prior and 12 months following protocol implementation. Adherence of 80% within 12 months was partially achieved in patients diagnosed in our hospital; in pretreated patients, adherence was not achieved. Maximum phenobarbital concentrations were decreased (56.8 vs 41.0 µg/mL), fewer patients progressed from seizures to status epilepticus (46% vs 36%), and hospital length of stay decreased by 9.7 days in survivors. In conclusion, standardized, protocol-driven treatment of neonatal status epilepticus improves consistency and short-term outcome.

Bivalirudin use in an infant with persistent clotting on unfractionated heparin.

Bivalirudin is a direct thrombin inhibitor approved for use in adult patients with heparin-induced thrombocytopenia (HIT) undergoing percutaneous coronary intervention. Recently, its use in the pediatric population has increased due to its anti-thrombin-independent mechanism of action. As heparin products produce great inter- and intraindividual variability in pediatric patients, often due to decreased anti-thrombin concentrations in the first year of life, some practitioners have turned to direct thrombin inhibitors, such as bivalirudin, for more predictable pharmacokinetics and effects on bound and circulating thrombin. We report our experience using bivalirudin in a 2-month-old female with recurrent systemic thrombi despite continuous unfractionated heparin infusion. Due to the patient's inability to maintain therapeutic activated partial thromboplastin time (aPTT) values during heparin infusion, bivalirudin was initiated at 0.1 mg/kg/h and increased due to subtherapeutic aPTTs to a maximum of 0.58 mg/kg/h. Therapeutic aPTTs were achieved at the increased dose; however, the patient's worsening renal impairment with resultant drug accumulation and overwhelming sepsis on day 5 of therapy led to discontinuation of the infusion and the initiation of comfort measures.

Summary of ASHP/IDSA/SIDP vancomycin monitoring recommendations: a focus on osteomyelitis.

Vancomycin has been used extensively for the treatment of Gram-positive bacterial infections, especially in cases of methicillin-resistant Staphylococcus aureus (MRSA). Despite long-term use, many uncertainties have remained regarding appropriate dosing, monitoring, and toxicity risks. In January 2009, a committee representing the American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), and the Society of Infectious Diseases Pharmacists (SIDP) released recommendations for vancomycin monitoring. As osteomyelitis patients are frequent recipients of vancomycin, this article provides a summary of the recommendations in reference to loading and maintenance doses, trough concentration monitoring, frequency of monitoring, and risk of toxicities.