BACKGROUND: Globally, over 400,000 neonatal deaths in 2015 were attributed to sepsis, however, the incidence and etiologies of these infections are largely unknown in low-middle income countries. We aimed to determine incidence and etiology of community-acquired early-onset (<72 hours age) sepsis (EOS) using culture and molecular diagnostics. METHODS: This was a prospective observational study, in which we conducted a surveillance for pathogens using a combination of blood culture and a polymerase chain reaction (PCR)-based test. Blood culture was performed on all neonates with suspected EOS. Among the subset fulfilling criteria for protocol-defined EOS, blood and nasopharyngeal (NP) respiratory swabs were tested by quantitative real-time reverse-transcriptase PCR using a Taqman Array Card (TAC) with 15 bacterial and 12 viral targets. Blood and NP samples from 312 healthy newborns were also tested by TAC to estimate background positivity rates. We used variant latent-class methods to attribute etiologies and calculate pathogen-specific proportions and incidence rates. RESULTS: We enrolled 2,624 neonates with suspected EOS and from these 1,231 newborns met criteria for protocol-defined EOS (incidence- 39.3/1,000 live-births). Using the partially latent-class modelling, only 26.7% cases with protocol-defined EOS had attributable etiology, and the largest pathogen proportion were Ureaplasma spp. (5.4%; 95%CI: 3.6-8.0) and group B Streptococcus (GBS) (4.8%; 95%CI: 4.1-5.8), and no etiology was attributable for 73.3% of cases. Blood cultures were positive in 99/1,231 (8.0%) with protocol-defined EOS (incidence- 3.2/1,000 live-births). Leading pathogens on blood culture included GBS (35%) and viridans streptococci (24%). Ureaplasma spp. was the most common organism identified on TAC among cases with protocol-defined EOS. CONCLUSION: Using a combination of blood culture and a PCR-based test the common pathogens isolated in neonates with sepsis were Ureaplasma spp. and GBS. Despite documenting higher rates of protocol-defined EOS and using a combination of tests, the etiology for EOS remains elusive.

BACKGROUND: Using antibiotics appropriately is critical to slow spread of antibiotic resistance, a major public health problem. Children, especially young children, receive more antibiotics than other age groups. Our objective was to describe antibiotic use in children in the United States (US) and use of azithromycin, which is recommended infrequently for pediatric conditions. METHODS: We used QuintilesIMS Xponent 2013 data to calculate the number and rate of oral antibiotic prescriptions for children by age (0-2, 3-9 and 10-19 years) and agent. We used log-binomial regression to calculate adjusted prevalence rations (PR) and 95% confidence intervals (CI) to determine if specialty and patient age were associated with azithromycin selection when an antibiotic was prescribed. RESULTS: In 2013, 66.8 million antibiotics were prescribed to US children aged ≤19 years (813 antibiotic prescriptions per 1000 children). Amoxicillin and azithromycin were the two most commonly prescribed agents (23.1 million courses, 35% of all antibiotics; 12.2 million, 18%; respectively). Most antibiotics for children were prescribed by pediatricians (39%) and family practitioners (15%). Family practitioners were more likely to select azithromycin when an antibiotic was prescribed in all age groups than pediatricians (for children aged 0-2 years: PR 1.79, 95% CI, 1.78-1.80; 3-9 years: 1.40, 1.40-1.40; and 10-19 years: 1.18, 1.18-1.18). CONCLUSION: Despite infrequent pediatric recommendations, variations in pediatric azithromycin use may suggest inappropriate antibiotic selection. Public health interventions focused on improving antibiotic selection in children as well as reducing antibiotic overuse are needed.

BACKGROUND: An increase in Mycoplasma pneumoniae-associated Stevens-Johnson syndrome (SJS) cases at a Colorado pediatric hospital led to an outbreak investigation. We describe the epidemiologic and molecular characteristics of M. pneumoniae among SJS case-patients and surrounding community members during the outbreak. METHODS: M. pneumoniae PCR-positive respiratory specimens from 5 Colorado hospitals and 4 referral laboratories underwent confirmatory PCR testing; positive specimens then underwent multilocus variable-number tandem-repeat analysis (MLVA) and macrolide resistance testing. Three SJS-M. pneumoniae case-patient households were surveyed using a standardized questionnaire, and nasopharyngeal/oropharyngeal swabs were obtained from all consenting/assenting household contacts. ICD-9 codes were used to identify pneumonia cases among Colorado patients aged 5-21 years from January 2009- March 2014. RESULTS: Three different M. pneumoniae MLVA types were identified among the 5 SJS case-patients with confirmed infection; MLVA type 3-X-6-2 was seen more commonly in SJS case-patients (60%) than in 69 non-SJS community specimens (29%). Macrolide resistance was identified in 7% of community specimens but not among SJS case-patients. Of 15 household contacts, 5 (33%) were M. pneumoniae-positive; all MLVA types were identical to those of the corresponding SJS case-patient, although the specimen from one contact was macrolide-resistant. Overall pneumonia cases as well as those caused by M. pneumoniae specifically peaked in October, 2013, coinciding with the SJS outbreak. CONCLUSIONS: The outbreak of M. pneumoniae-associated SJS may have been associated with a community outbreak of M. pneumoniae; clinicians should be aware of the M. pneumoniae-SJS relationship. Household transmission of M. pneumoniae was common within the households investigated.

Each year in the United States, approximately two million persons become infected with antibiotic-resistant bacteria, at least 23,000 persons die as a direct result of these infections, and many more die from conditions complicated by a resistant infection. Antibiotic-resistant infections contribute to poor health outcomes, higher health care costs, and use of more toxic treatments. Although emerging resistance mechanisms are being identified and resistant infections are on the rise, new antibiotic development has slowed considerably.

BACKGROUND: Stevens-Johnson syndrome (SJS) is an uncommon, sporadic disease and outbreaks are rare. In November 2013, an outbreak of SJS was identified at Children's Hospital Colorado. METHODS: Outbreak cases were children aged 5-21 with a discharge diagnosis of SJS admitted from September 1 to November 30, 2013. Medical charts were reviewed using standardized data collection forms. Respiratory specimens were tested for viruses and Mycoplasma pneumoniae (Mp) by polymerase chain reaction (PCR). We conducted a separate 4-year retrospective case-control study comparing hospitalized SJS cases with and without evidence of Mp infection. RESULTS: During the outbreak, 8 children met SJS criteria. Median age was 11.5 years (range 8-16 years); 5 (63%) were boys and 5 (63%) were Mp-PCR-positive. Of the 5 PCR-positive children, none had preceding medication exposure, and all had radiographic pneumonia. All outbreak Mp isolates were macrolide susceptible. The retrospective case-control analysis showed that Mp-associated SJS episodes (n = 17) were more likely to have pneumonia (odds ratio [OR] 10.0, confidence interval [CI] 1.3-5.1), preceding respiratory symptoms (OR 30.0, CI 1.6-72.6), an erythrocyte sedimentation rate ≥35 mg/dL (OR 22.8, CI 2.1-244.9), and ≤3 affected skin sites (OR 4.5, CI 1.2-17.4) than non-Mp-associated SJS episodes (n = 23). CONCLUSIONS: We report the largest outbreak of SJS in children, which was also predominately associated with Mp infection. Mp-associated SJS was associated with a distinct clinical presentation that included less extensive skin disease, an elevated erythrocyte sedimentation rate, and evidence of a preceding respiratory infection.

BACKGROUND: Healthcare-associated Legionnaires' disease (LD) is a preventable pneumonia with a 30% case-fatality rate. The Centers for Disease Control and Prevention guidelines recommend a high index of suspicion for the diagnosis of healthcare-associated LD. We characterized an outbreak and evaluated contributing factors in a hospital using copper-silver ionization for prevention of Legionella growth in water. METHODS: Through medical chart review at a large, urban tertiary care hospital in November 2012, we identified patients diagnosed with LD during 2011-2012. Laboratory-confirmed cases were categorized as definite, probable, and not healthcare-associated based on time spent in the hospital during the incubation period. We performed an environmental assessment of the hospital, including collection of samples for Legionella culture. Clinical and environmental isolates were compared by genotyping. Copper and silver ion concentrations were measured in 11 water samples. RESULTS: We identified five definite and 17 probable healthcare-associated LD cases; six case-patients died. Of 25 locations (mostly potable water) where environmental samples were obtained for Legionella-specific culture, all but two showed Legionella growth; eleven isolates were identical to three clinical isolates by sequence-based typing. Mean copper and silver concentrations were at or above the manufacturer's recommended target for Legionella control. Despite this, all samples where copper and silver concentrations were tested showed Legionella growth. CONCLUSIONS: This outbreak was linked to the hospital's potable water system and highlights the importance of maintaining a high index of suspicion for healthcare-associated LD, even in the setting of a long-term disinfection program.