Joseph B. Cantey

Chorioamnionitis and Culture-Confirmed, Early-Onset Neonatal Infections

BACKGROUND: Current guidelines for prevention of neonatal group B streptococcal disease recommend diagnostic evaluations and empirical antibiotic therapy for well-appearing, chorioamnionitis-exposed newborns. Some clinicians question these recommendations, citing the decline in early-onset group B streptococcal disease rates since widespread intrapartum antibiotic prophylaxis implementation and potential antibiotic risks. We aimed to determine whether chorioamnionitis-exposed newborns with culture-confirmed, early-onset infections can be asymptomatic at birth. METHODS: Multicenter, prospective surveillance for early-onset neonatal infections was conducted during 2006–2009. Early-onset infection was defined as isolation of a pathogen from blood or cerebrospinal fluid collected ≤72 hours after birth. Maternal chorioamnionitis was defined by clinical diagnosis in the medical record or by histologic diagnosis by placental pathology. Hospital records of newborns with early-onset infections born to mothers with chorioamnionitis were reviewed retrospectively to determine symptom onset. RESULTS: Early-onset infections were diagnosed in 389 of 396 586 live births, including 232 (60%) chorioamnionitis-exposed newborns. Records for 229 were reviewed; 29 (13%) had no documented symptoms within 6 hours of birth, including 21 (9%) who remained asymptomatic at 72 hours. Intrapartum antibiotic prophylaxis exposure did not differ significantly between asymptomatic and symptomatic infants (76% vs 69%; P = .52). Assuming complete guideline implementation, we estimated that 60 to 1400 newborns would receive diagnostic evaluations and antibiotics for each infected asymptomatic newborn, depending on chorioamnionitis prevalence. CONCLUSIONS: Some infants born to mothers with chorioamnionitis may have no signs of sepsis at birth despite having culture-confirmed infections. Implementation of current clinical guidelines may result in early diagnosis, but large numbers of uninfected asymptomatic infants would be treated.

Assessment of empirical antibiotic therapy optimisation in six hospitals: an observational cohort study

BACKGROUND Modification of empirical antimicrobials when warranted by culture results or clinical signs is recommended to control antimicrobial overuse and resistance. We aimed to assess the frequency with which patients were started on empirical antimicrobials, characteristics of the empirical regimen and the clinical characteristics of patients at the time of starting antimicrobials, patterns of changes to empirical therapy at different timepoints, and modifiable factors associated with changes to the initial empirical regimen in the first 5 days of therapy. METHODS We did a chart review of adult inpatients receiving one or more antimicrobials in six US hospitals on 4 days during 2009 and 2010. Our primary outcome was the modification of antimicrobial regimen on or before the 5th day of empirical therapy, analysed as a three-category variable. Bivariate analyses were used to establish demographic and clinical variables associated with the outcome. Variables with p values below 0·1 were included in a multivariable generalised linear latent and mixed model with multinomial logit link to adjust for clustering within hospitals and accommodate a non-binary outcome variable. FINDINGS Across the six study sites, 4119 (60%) of 6812 inpatients received antimicrobials. Of 1200 randomly selected patients with active antimicrobials, 730 (61%) met inclusion criteria. At the start of therapy, 220 (30%) patients were afebrile and had normal white blood cell counts. Appropriate cultures were collected from 432 (59%) patients, and 250 (58%) were negative. By the 5th day of therapy, 12·5% of empirical antimicrobials were escalated, 21·5% were narrowed or discontinued, and 66·4% were unchanged. Narrowing or discontinuation was more likely when cultures were collected at the start of therapy (adjusted OR 1·68, 95% CI 1·05-2·70) and no infection was noted on an initial radiological study (1·76, 1·11-2·79). Escalation was associated with multiple infection sites (2·54, 1·34-4·83) and a positive culture (1·99, 1·20-3·29). INTERPRETATION Broad-spectrum empirical therapy is common, even when clinical signs of infection are absent. Fewer than one in three inpatients have their regimens narrowed within 5 days of starting empirical antimicrobials. Improved diagnostic methods and continued education are needed to guide discontinuation of antimicrobials. FUNDING US Centers for Disease Control and Prevention, Division of Healthcare Quality Promotion; Robert Wood Johnson Foundation; US Department of Veterans Administration; US Department of Homeland Security.

Discordance between staphylococcus aureus nasal colonization and skin infections in children

We examined nasal carriage of Staphylococcus aureus in otherwise healthy children presenting with skin and soft tissue infections. We found high rates of nasal colonization with S. aureus, but significant discordance between nasal and wound isolates. Recurrent skin and soft tissue infections were common but unrelated to baseline methicillin-resistant S. aureus nasal colonization status.

Randomized Controlled Trial of Cephalexin Versus Clindamycin for Uncomplicated Pediatric Skin Infections

OBJECTIVE: To compare clindamycin and cephalexin for treatment of uncomplicated skin and soft tissue infections (SSTIs) caused predominantly by community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA). We hypothesized that clindamycin would be superior to cephalexin (an antibiotic without MRSA activity) for treatment of these infections. PATIENTS AND METHODS: Patients aged 6 months to 18 years with uncomplicated SSTIs not requiring hospitalization were enrolled September 2006 through May 2009. Eligible patients were randomly assigned to 7 days of cephalexin or clindamycin; primary and secondary outcomes were clinical improvement at 48 to 72 hours and resolution at 7 days. Cultures were obtained and tested for antimicrobial susceptibilities, pulsed-field gel electrophoresis type, and Panton-Valentine leukocidin status. RESULTS: Of 200 enrolled patients, 69% had MRSA cultured from wounds. Most MRSA were USA300 or subtypes, positive for Panton-Valentine leukocidin, and clindamycin susceptible, consistent with CA-MRSA. Spontaneous drainage occurred or a drainage procedure was performed in 97% of subjects. By 48 to 72 hours, 94% of subjects in the cephalexin arm and 97% in the clindamycin arm were improved (P = .50). By 7 days, all subjects were improved, with complete resolution in 97% in the cephalexin arm and 94% in the clindamycin arm (P = .33). Fevers and age less than 1 year, but not initial erythema > 5 cm, were associated with early treatment failures, regardless of antibiotic used. CONCLUSIONS: There is no significant difference between cephalexin and clindamycin for treatment of uncomplicated pediatric SSTIs caused predominantly by CA-MRSA. Close follow-up and fastidious wound care of appropriately drained, uncomplicated SSTIs are likely more important than initial antibiotic choice.

Antimicrobial stewardship in the NICU

There are unique challenges to antimicrobial stewardship in neonatal intensive care units (NICUs). Diagnosis of infection is difficult as neonates can have nonspecific signs and symptoms. Between and within NICUs, significant variation exists in the treatment duration of suspected sepsis and pneumonia. Development of multidisciplinary teams and meaningful metrics are essential for sustainable antibiotic stewardship. Potential stewardship interventions include optimizing culturing techniques, guiding empiric therapy by NICU-specific antibiograms, using ancillary laboratory tests, and promptly discontinuing therapy once infection is no longer suspected. Use of large neonatal databases can be used to benchmark antibiotic use and conduct comparative effectiveness research.

Prospective surveillance of antibiotic use in the neonatal intensive care unit: results from the SCOUT study.

Background: Prolonged or unnecessary antibiotic use is associated with adverse outcomes in neonates. Our objectives were to quantify all antibiotic use in a Level-III neonatal intensive care unit and to identify scenarios where their use could be reduced. Methods: Surveillance and evaluation of all antibiotic use provided to every infant admitted to a Level-III neonatal intensive care unit from 10/3/11 to 11/30/12 was performed. Types of antibiotics, reasons for their initiation, discontinuation and duration, as well as clinical, laboratory and outcome data were recorded. Antibiotic use was quantified by days of therapy (DOT) per 1000 patient-days (PD). Results: A total of 1607 infants were included. The total antibiotic use was 9165 DOT (343.2 DOT/1000 PD; 5.7 DOT/infant). Seventy-two percent of infants received 1 (43%) or more (29%) courses of antibiotics. Gentamicin (46%), ampicillin (39%) and oxacillin (8%) were the most frequently used agents. Ninety-four percent of antibiotic use (323 DOT/1000 PD) was empiric therapy for suspected infection. Sixty-three percent (216.2 DOT/1000 PD) was discontinued at approximately 48 hours when cultures were sterile (68% >48 hours, 32% ⩽48 hours). Twenty-six percent of all antibiotic use (89.4 DOT/1000 PD) was therapy for ≥5 days despite sterile cultures; pneumonia (16%) and “culture-negative” sepsis (8%) were the major contributors. Five percent (17.4 DOT/1000 PD) of antibiotic use was for culture-proven sepsis, 5% (16.6 DOT/1000 PD) was penicillin prophylaxis for group B Streptococcus and 1% (3.5 DOT/1000 PD) was preprocedural prophylaxis. Conclusions: Narrow-spectrum therapy accounted for >92% of antibiotic use and would not be monitored by most stewardship programs. Only 5% of antibiotic usage was due to culture-proven infection. Pneumonia and “culture-negative” sepsis were frequent reasons for prolonged therapy; further study of these conditions may allow reduction in treatment duration.

Bloodstream Infections: Epidemiology and Resistance

Bloodstream infections in the neonatal intensive care unit (NICU) are associated with many adverse outcomes in infants, including increased length of stay and cost, poor neurodevelopmental outcomes, and death. Attention to the insertion and maintenance of central lines, along with careful review of when the catheters can be safely discontinued, can minimize central-line-associated bloodstream infections rates. Good antibiotic stewardship can further decrease the incidence of bloodstream infections, minimize the emergence of drug-resistant organisms or Candida as pathogens in the NICU, and safeguard the use of currently available antibiotics for future infants.

Use of Blood Polymerase Chain Reaction Testing for Diagnosis of Herpes Simplex Virus Infection

The use of herpes simplex virus (HSV) polymerase chain reaction for diagnosis of HSV disease involving the central nervous system has not translated into widespread use for the detection of DNAemia. We report our 6-year experience using blood polymerase chain reaction testing for HSV infection in neonates and older children with HSV disease.

Indications and Types of Antibiotic Agents Used in 6 Acute Care Hospitals, 2009–2010: A Pragmatic Retrospective Observational Study

BACKGROUND To design better antimicrobial stewardship programs, detailed data on the primary drivers and patterns of antibiotic use are needed. OBJECTIVE To characterize the indications for antibiotic therapy, agents used, duration, combinations, and microbiological justification in 6 acute-care US facilities with varied location, size, and type of antimicrobial stewardship programs. DESIGN, PARTICIPANTS, AND SETTING Retrospective medical chart review was performed on a random cross-sectional sample of 1,200 adult inpatients, hospitalized (>24 hrs) in 6 hospitals, and receiving at least 1 antibiotic dose on 4 index dates chosen at equal intervals through a 1-year study period (October 1, 2009-September 30, 2010). METHODS Infectious disease specialists recorded patient demographic characteristics, comorbidities, microbiological and radiological testing, and agents used, dose, duration, and indication for antibiotic prescriptions. RESULTS On the index dates 4,119 (60.5%) of 6,812 inpatients were receiving antibiotics. The random sample of 1,200 case patients was receiving 2,527 antibiotics (average: 2.1 per patient); 540 (21.4%) were prophylactic and 1,987 (78.6%) were therapeutic, of which 372 (18.7%) were pathogen-directed at start. Of the 1,615 empirical starts, 382 (23.7%) were subsequently pathogen-directed and 1,231 (76.2%) remained empirical. Use was primarily for respiratory (27.6% of prescriptions) followed by gastrointestinal (13.1%) infections. Fluoroquinolones, vancomycin, and antipseudomonal penicillins together accounted for 47.1% of therapy-days. CONCLUSIONS Use of broad-spectrum empirical therapy was prevalent in 6 US acute care facilities and in most instances was not subsequently pathogen directed. Fluoroquinolones, vancomycin, and antipseudomonal penicillins were the most frequently used antibiotics, particularly for respiratory indications. Infect. Control Hosp. Epidemiol. 2015;37(1):70-79.

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.