The Mortality of Congenital Syphilis.

OBJECTIVES: To document the case-fatality rate (CFR) of congenital syphilis diagnosed by molecular tools and rabbit infectivity testing (RIT) of clinical specimens in addition to standard evaluation and to compare that with the CFR using the Centers for Disease Control and Prevention (CDC) surveillance case definition. STUDY DESIGN: Prospective, single site, cohort study of all cases of syphilis among mothers and their infants from 1984 to 2002. The diagnosis of congenital syphilis was determined using IgM immunoblotting, polymerase chain reaction, and RIT of fetal or infant specimens in addition to clinical, laboratory, and radiographic criteria. Data were retrospectively reviewed to ascertain fetal and neonatal mortality. RESULTS: During the 18-year study, there were 191 cases of congenital syphilis confirmed by abnormalities on clinical, laboratory, or radiographic evaluation and/or positive serum IgM immunoblot, blood polymerase chain reaction, or blood/cerebrospinal fluid RIT. Of the 191 cases, 59 died for a CFR of 31%. Of the 59 deaths, 53 (90%) were stillborn and 6 (10%) died in the neonatal period. The majority (74%, 39/53) of stillbirths occurred in the third trimester. The CDC surveillance case definition correctly identified all infants with congenital syphilis, but the CDC CFR was 10% which underestimated the CFR by more than 300%. CONCLUSIONS: Our findings corroborate the high sensitivity of the CDC surveillance definition for congenital syphilis but highlight its poor estimation of its associated mortality. The CFR among infected progeny of pregnant women with syphilis was 31%, due mostly to demise in the third trimester and as such highlights the need for detection and appropriate treatment of syphilis during pregnancy.

Neonatal bloodstream infections.

PURPOSE OF REVIEW: Neonatal bloodstream infections (BSI) are a major contributor to morbidity and mortality within neonatal intensive care units. BSI, including central line-associated BSI, have decreased over the past 15 years but remain common in extremely preterm infants. The purpose of this review is to highlight recent advances in the causes, diagnosis, management, and prevention of neonatal BSI. RECENT FINDINGS: Continued quality improvement efforts and bundles have reduced BSI incidence, and novel approaches are highlighted. An update of emerging pathogens as well as traditional pathogens with novel antimicrobial resistance, which are an increasingly common cause of neonatal BSI, is included. Finally, current and future investigations into serum or noninvasive biomarkers for neonatal BSI are reviewed. SUMMARY: Neonatal BSIs continue to decrease due to enhanced infection control and prevention techniques. However, many challenges remain, including emerging bacterial and fungal resistance and the continued need for novel diagnostics that hasten time to pathogen identification and effective treatment. This review of the past 18 months highlights the rapid changes in this area. Ongoing efforts to reduce the morbidity and mortality caused by neonatal BSI must remain a priority.

Short-Term Complications Associated with Surgical Ligation of Patent Ductus Arteriosus in ELBW Infants: A 25-Year Cohort Study.

OBJECTIVE: This article aims to determine the incidence of short-term complications of surgical patent ductus arteriosus (PDA) ligations, the factors associated with those complications, and whether complications are associated with poor long-term outcomes. STUDY DESIGN: Retrospective cohort study of all extremely low birth weight (ELBW, < 1,000 g) infants who underwent surgical PDA ligation at a single-center neonatal intensive care unit from 1989 to 2015. Demographic, clinical, and laboratory data were reviewed. The primary outcome was development of a short-term (< 2 weeks from ligation) surgical complication. Secondary outcomes include bronchopulmonary dysplasia (BPD), length of stay, and mortality. RESULTS: A total of 180 ELBW infants were included; median gestational age and birth weight was 24 weeks and 683 g, respectively, and 44% of infants had at least one short-term complication. Need for vasopressors (33%) was the most common medical complication and vocal cord paralysis (9%) was the most common surgical complication. Younger corrected gestational age at time of repair was associated with increased risk for complications. Mortality, length of stay, and BPD rates were similar between infants with and without complications. CONCLUSION: Serious complications were seen in a minority of infants. Additional research is needed to determine if short-term complications are associated with long-term adverse outcomes.

Early Antibiotic Exposure and Adverse Outcomes in Preterm, Very Low Birth Weight Infants.

OBJECTIVES: To determine whether antibiotic use in the first 14 postnatal days in preterm, very low birth weight (birth weight of ≤1500 g) infants is associated with risk after 14 days of age for late-onset sepsis, necrotizing enterocolitis (NEC), or death after controlling for severity of illness using the Clinical Risk Index in Babies II score, and determine whether duration of antibiotic exposure was associated with risk of adverse outcomes. STUDY DESIGN: This retrospective cohort study included very low birth weight infants born at ≤326/7 weeks of gestation admitted to the neonatal intensive care unit from September 2010 to June 2014. Infants were excluded if they had major congenital anomalies or culture-proven sepsis, NEC, or death during the first 14 days of life. Antibiotic exposure was recorded as days of therapy and length of therapy in days. RESULTS: Of 374 infants, 70 (19%) had late-onset sepsis, NEC, or death after 14 days of age. The median number of antibiotic days of therapy and length of therapy were 5.5 and 3.0, respectively. In multivariate analysis after controlling for severity of illness, each antibiotic day of therapy was associated with a 1.24 times increased risk of sepsis, NEC, or death (OR, 1.24; 95% CI, 1.17-1.31). Risk was similar when length of therapy was used (OR, 1.47; 95% CI, 1.32-1.64). CONCLUSIONS: After controlling for severity of illness, each day of antibiotic therapy provided to preterm, very low birth weight infants in the first 2 weeks of age is associated with an increased risk of late-onset sepsis, NEC, or death.

Antibiotic Exposure and Risk for Death or Bronchopulmonary Dysplasia in Very Low Birth Weight Infants.

We assessed the association between antibiotic exposure in the first 2 weeks of life and development of bronchopulmonary dysplasia in a cohort of very low birth weight infants. After controlling for the severity of illness, each additional day of antibiotic therapy was associated with both an increased risk for and severity of bronchopulmonary dysplasia.

Risk of Early-Onset Sepsis following Preterm, Prolonged Rupture of Membranes with or without Chorioamnionitis.

OBJECTIVE: This study aims to determine whether preterm prolonged rupture of membranes (PPROM) increases the risk for early-onset sepsis (EOS) in preterm infants. STUDY DESIGN: Retrospective cohort study of infants 30 to 34 weeks' gestation from 2005 to 2014. Exposure to PPROM (rupture of membranes ≥ 18 hours) or chorioamnionitis (maternal temperature ≥ 38°C during delivery plus notation of chorioamnionitis in the medical record) was collected. The primary outcome was proven or suspected EOS. RESULTS: A total of 2,192 infants were included. Overall, 1,750 (80%) were not exposed to PPROM or chorioamnionitis (group 1), 381 (17%) were exposed to PPROM without chorioamnionitis (group 2), and 61 (3%) were exposed to chorioamnionitis ± PPROM (group 3). There was no difference in the incidence of proven or suspected EOS between groups 1 and 2 (5.4 vs. 5.5%, p = 0.86). Group 3 had a higher rate of EOS (24.6%) relative to groups 1 and 2 (p < 0.001). In multivariate analysis, risk of EOS was 4.1 times higher in infants exposed to chorioamnionitis. PPROM did not increase the risk of EOS in bivariate or multivariate analysis. CONCLUSION: In the absence of chorioamnionitis, PPROM does not increase the risk of proven or clinically suspected EOS in 30 to 34 weeks' gestation infants.

Antibiotic Stewardship Challenges in a Referral Neonatal Intensive Care Unit.

BACKGROUND: Antibiotic overuse in neonates is associated with adverse outcomes. Data are limited to guide antibiotic stewardship in the neonatal intensive care unit (NICU). Our objective was to identify areas for antibiotic stewardship improvement in a referral NICU. METHODS: Retrospective review of antibiotic use administered to infants admitted to a referral NICU compared with an inborn NICU. Antibiotic use was quantified by days of therapy (DOT) per 1,000 patient-days (PD). RESULTS: A total of 78% of referral NICU infants received ≥ 1 course of antibiotics. Infants in the referral NICU received more antibiotic DOT/1,000 PD than in the inborn NICU (558.9 vs. 343.2, p < 0.001), with a higher proportion of broad-spectrum therapy. For infants in the referral NICU, 39% of antibiotic courses were started at the transferring hospital; these were broader in spectrum (28 vs. 20%, p < 0.001) and less likely to be de-escalated or discontinued at 48 to 72 hours (58 vs. 87%, p < 0.001) than courses started after transfer. CONCLUSIONS: Compared with the inborn NICU, suspected sepsis in the referral NICU accounted for more antibiotic utilization, which was broad-spectrum and less likely to be de-escalated. Stewardship interventions should include reserving broad-spectrum therapy for infants with risk factors and de-escalating promptly once culture results become available.

Maternal titers after adequate syphilotherapy during pregnancy.

BACKGROUND: We aimed to construct a timeline for nontreponemal titer decline specific to pregnancy and evaluate factors associated with inadequate decline by delivery. METHODS: This was a retrospective medical records review from September 1984 to June 2011 of women diagnosed with syphilis after 18 weeks of gestation. Women were treated according to stage of syphilis per Centers for Disease Control and Prevention guidelines. Patients with both pretreatment and delivery titers were included for data analysis. Demographics, stage of syphilis, maternal titers, delivery, and infant outcomes were recorded. Standard statistical analyses were performed for categorical and continuous data. The titer decline was analyzed using mixed-effects regression modeling. RESULTS: A total of 166 patients met inclusion criteria. Mean gestational age at treatment was 29.1 ± 5 weeks, and 93 (56%) women were diagnosed with early-stage syphilis. For all stages of syphilis, maternal titers declined after syphilotherapy. Pretreatment titers were higher and declined more rapidly in primary and secondary disease than in latent-stage disease and syphilis of unknown duration. Sixty-three (38%) patients achieved a 4-fold decline by delivery. Patients without a 4-fold decline by delivery were older (24.6 vs 21.5 years; P < .001), treated later in pregnancy (30.3 vs 27.3 weeks; P < .001), diagnosed with latent syphilis or syphilis of unknown duration, and had less time from treatment to delivery (7.8 vs 11.1 weeks; P < .001). CONCLUSIONS: Maternal serologic response during pregnancy after adequate syphilotherapy varied by stage of disease. Failure to achieve a 4-fold decline in titers by delivery is more a reflection of treatment timing than of treatment failure.

Lack of clinical utility of urine gram stain for suspected urinary tract infection in pediatric patients.

Urinary tract infection (UTI) is one of the most common infections in children. Urine culture remains the gold standard for diagnosis, but the utility of urine Gram stain relative to urinalysis (UA) is unclear. We reviewed 312 pediatric patients with suspected UTI who had urine culture, UA, and urine Gram stain performed from a single urine specimen. UA was considered positive if ≥10 leukocytes per oil immersion field were seen or if either nitrates or leukocyte esterase testing was positive. Urine Gram stain was considered positive if any organisms were seen. Sensitivity, specificity, and positive and negative predictive values were calculated using urine culture as the gold standard. Thirty-seven (12%) patients had a culture-proven UTI. Compared to urine Gram stain, UA had equal sensitivity (97.3% versus 97.5%) and higher specificity (85% versus 74%). Empirical therapy was prescribed before the Gram stain result was known in 40 (49%) patients and after in 42 (51%) patients. The antibiotics chosen did not differ between the two groups (P=0.81), nor did they differ for patients with Gram-negative rods on urine Gram stain compared to those with Gram-positive cocci (P=0.67). From these data, we conclude that UA has excellent negative predictive value that is not enhanced by urine Gram stain and that antibiotic selection did not vary based on the urine Gram stain result. In conclusion, the clinical utility of urine Gram stain does not warrant the time or cost it requires.

The mortality of neonatal herpes simplex virus infection.

This retrospective study characterized the clinical course of 13 neonates who died with herpes simplex virus infection from 2001 to 2011, representing a 26% case-fatality rate. Fatal disease developed at ≤ 48 hours of age in one-third of infants, was mostly disseminated disease, and occurred despite early administration of high-dose acyclovir therapy.

Herpes Simplex Virus DNAemia Preceding Neonatal Disease.

Polymerase chain reaction testing of blood for herpes simplex virus (HSV) is recommended for newborns delivered to mothers with active genital HSV lesions at delivery. We report an infant who had a positive blood HSV polymerase chain reaction test before the onset of clinical signs of HSV disease.

Empiric Antibiotics for Serious Bacterial Infection in Young Infants: Opportunities for Stewardship.

OBJECTIVES: To evaluate the causative agents of serious bacterial infection (SBI) in young infants and the optimal approach to empiric antibiotic therapy for infants with SBI. METHODS: From May 1, 2011, to December 1, 2013, pertinent clinical data were collected on previously well infants 60 days or younger with SBI as defined by a positive bacterial culture from a sterile site. Infants were identified by prospective surveillance of admissions and daily review of microbiology records. RESULTS: Two hundred sixty-five infants with SBI were identified. Mean age was 32 days (SD ±16.6 days). Twenty-nine infants had meningitis, 66 had bacteremia (37 with concomitant urinary tract infection), and 170 had urinary tract infection alone. No methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus sp., or penicillin-resistant Streptococcus pneumoniae were identified. Four extended-spectrum ß-lactamase-producing gram-negative bacilli were seen. Empiric therapy was ampicillin and gentamicin (n = 116, 44%) or third-generation cephalosporin based (n = 149, 56%). Ampicillin and gentamicin, with third-generation cephalosporins reserved for cases where meningitis is suspected, would have provided effective coverage for 98.5% of infants and unnecessarily broad therapy for 4.3%. Third-generation cephalosporins with ampicillin would have been effective for 98.5% of infants and unnecessarily broad for 83.8%. Third-generation cephalosporin monotherapy was less effective than either combination (P < 0.001). Fifty-seven percent of broad spectrum empiric therapy was continued despite culture results allowing de-escalation. CONCLUSIONS: Ampicillin/gentamicin remains an effective empiric regimen for infants 60 days or younger with suspected SBI. Use of a third-generation cephalosporin for suspected meningitis is appropriate, but cerebrospinal fluid must be obtained promptly to guide appropriate therapy.

Pertussis: a persistent cause of morbidity and mortality in young infants.

In 2012, a pertussis outbreak in Dallas County resulted in the deaths of 4 children (3, unvaccinated; 2, <60 days of age). Despite recommendations that include immunization of women preferably during the third trimester of pregnancy or postpartum, household contacts ("cocooning"), and infants as early as 42 days of age, challenges in pertussis prevention remain.

Brain magnetic resonance imaging of infants with bacterial meningitis.

OBJECTIVES: To describe the results of brain magnetic resonance imaging (MRI) of infants with bacterial meningitis and how the findings affected clinical management. STUDY DESIGN: This retrospective study included all infants <12 months of age who were hospitalized at Children's Medical Center, Dallas and had culture-confirmed bacterial meningitis and a brain MRI from January 1, 2001 to December 1, 2011. Infants were identified by review of all positive bacterial cultures of cerebrospinal fluid (CSF) from the Children's Medical Center Microbiology Laboratory. Demographic, clinical, laboratory, and neuroimaging data were reviewed. Infants with ventriculoperitoneal shunt or whose CSF culture yielded skin commensals were excluded. A neuroradiologist blinded to clinical information reviewed all MRI studies. RESULTS: Of the 440 infants who had a positive CSF culture result, 111 (25%) had a pathogen isolated from CSF and were enrolled in the study. Of these, 68% (75/111) had a brain MRI performed during the hospitalization; abnormalities included leptomeningeal enhancement (57%), cerebral infarct (43%), subdural empyema (52%), cerebritis (26%), hydrocephalus (20%), and abscess (11%). By multiple logistic regression analysis, infants with late seizures and an abnormal neurologic examination were more likely to have an abnormal MRI (P < .05). MRI results led to neurosurgical intervention in 23% of infants; a positive bacterial culture of CSF obtained >48 hours after initiation of antibiotic therapy was associated with neurosurgical intervention (P = .01). Fourteen (19%) infants with bacterial meningitis had a normal brain MRI. CONCLUSIONS: Brain MRIs were performed frequently and often were abnormal in infants with bacterial meningitis, leading to changes in clinical management.

Progression of ultrasound findings of fetal syphilis after maternal treatment.

OBJECTIVE: The purpose of this study was to evaluate ultrasound findings of fetal syphilis and to describe their progression after maternal treatment. STUDY DESIGN: This was a retrospective cohort study from September 1981 to June 2011 of seropositive women after 18 weeks of gestation who had an ultrasound before treatment to evaluate for fetal syphilis. Only those women who received treatment after the initial ultrasound scan, but before delivery, were included. If the initial ultrasound scan was abnormal, serial sonography was performed until resolution of the abnormality or delivery. Patient demographics, ultrasound findings, stage of syphilis, delivery, and infant outcomes were recorded. Standard statistical analyses were performed. Kaplan-Meier estimates were constructed to estimate time to resolution. RESULTS: Two hundred thirty-five women met the inclusion criteria; 73 of them (30%) had evidence of fetal syphilis on initial ultrasound scan. Abnormalities included hepatomegaly (79%), placentomegaly (27%), polyhydramnios (12%), ascites (10%) and abnormal middle cerebral arterial Doppler assessment (33%). After treatment, middle cerebral arterial Doppler assessment abnormalities, ascites, and polyhydramnios resolved first, followed by placentomegaly and finally hepatomegaly. Infant outcomes were available for 173 deliveries; of these, 32 infants (18%) were diagnosed with congenital syphilis. Congenital syphilis was more common when antenatal ultrasound abnormalities were present (39% vs 12%; P < .001). Infant examination findings at delivery were similar between women with and without an abnormal pretreatment ultrasound scan. However, in those infants with congenital syphilis, hepatomegaly was the most frequent abnormality found, regardless of antenatal ultrasound findings. CONCLUSION: Sonographic signs of fetal syphilis confer a higher risk of congenital syphilis at delivery for all maternal stages. Hepatomegaly develops early and resolves last after antepartum treatment.

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).

Prompt control of an outbreak caused by extended-spectrum ß-lactamase-producing Klebsiella pneumoniae in a neonatal intensive care unit.

OBJECTIVES: To assess the effectiveness of a set of multidisciplinary interventions aimed at limiting patient-to-patient transmission of extended-spectrum ß-lactamase-producing Klebsiella pneumoniae (ESBL-KP) during a neonatal intensive care unit (NICU) outbreak, and to identify risk factors associated with ESBL-KP colonization and disease in this setting. STUDY DESIGN: A 61-infant cohort present in the NICU during an outbreak of ESBL-KP from April 26, 2011, to May 16, 2011, was studied. Clinical characteristics were compared in infected/colonized infants and unaffected infants. A multidisciplinary team formulated an outbreak control plan that included (1) staff reeducation on recommended infection prevention measures; (2) auditing of hand hygiene and environmental services practices; (3) contact precautions; (4) cohorting of infants and staff; (5) alleviation of overcrowding; and (6) frequent NICU-wide screening cultures. Neither closure of the NICU nor culturing of health care personnel was instituted. RESULTS: Eleven infants in this level III NICU were infected/colonized with ESBL-KP. The index case was an 18-day-old infant born at 25 weeks' gestation who developed septicemia from ESBL-KP. Two other infants in the same room developed sepsis from ESBL-KP within 48 hours; both expired. Implementation of various infection prevention strategies resulted in prompt control of the outbreak within 3 weeks. The ESBL-KP isolates presented a single clone that was distinct from ESBL-KP identified previously in other units. Being housed in the same room as the index infant was the only risk factor identified by logistic regression analysis (P = .002). CONCLUSION: This outbreak of ESBL-KP affected 11 infants and was associated with 2 deaths. Prompt control with eradication of the infecting strain from the NICU was achieved with multidisciplinary interventions based on standard infection prevention practices.

Prevention of mother-to-infant transmission of influenza during the postpartum period.

OBJECTIVES: The optimal management of infants born to mothers with peripartum influenza infection is not known. The objective of this study is to describe our experience with a practice guideline that promotes rooming-in and breast-feeding and to determine whether infants managed in this way acquire influenza infection. STUDY DESIGN: All mothers diagnosed with influenza infection within 8 days of delivery and their infants were included. Demographics, clinical characteristics, and outcome data were collected. Mothers were contacted at ~1 month after giving birth to determine if their infants had developed any signs suggestive of influenza infection. RESULTS: Forty-two women were diagnosed with peripartum influenza over the 2003 to 2005 and 2009 to 2010 seasons. Median onset of symptoms was 3 days before delivery, and median day of diagnosis was 1 day before delivery. The 42 infants had a median gestational age of 39 weeks; none were born earlier than 35 weeks. Ninety-five percent of the infants roomed-in with their mothers. Follow-up information was available on 95% of infants by 1 month; no infants had illness suggestive of influenza through the follow-up period. CONCLUSION: A guideline for the management of infants born to mothers with peripartum influenza infection, based on attention to hand hygiene, antiviral treatment for mothers, and encouragement of rooming-in and breast-feeding, was not associated with mother-to-infant influenza transmission over three separate influenza seasons.