Hours Of Antibiotic Therapy Research Articles

1333. Prognostic Factors Associated with Complications of Acute Hematogenous Osteomyelitis in Children

Abstract Background The clinical presentation and management of acute hematogenous osteomyelitis (AHO) in children can vary significantly. Scores to predict acute complications utilize prolonged fever after antibiotics, bone abscess, suppurative arthritis, disseminated infection and delayed source control. By contrast, elevated CRP after 48-96 hours of therapy, disseminated disease and bone debridement are predictive of chronic complications. Such scoring systems have undergone limited validation. We examined factors associated with acute and chronic AHO complications at our center to identify other variables that may enhance published scores. Methods A retrospective chart review was conducted of all children 6 mo-18 years with AHO and with acute symptoms of < 14 days at Texas Children’s Hospital from January 2012 through December 2020. An acute complicated course was defined as treatment failure within 6 weeks of starting antibiotics, > 2 bone debridements, prolonged admission ( >14 days) and acute avascular necrosis. Chronic complications included growth arrest or limb leg discrepancy, pathologic fracture, avascular necrosis, chronic osteomyelitis or frozen joint. Statistical analysis was completed using STATA 17. Results 418 patients met the inclusion criteria. 106 (25.4%) had an acute complicated course. 51 (13.5%) of 377 followed had a chronic complication. Clinical factors associated with acute and chronic complications were very similar. Factors associated with either an acute complicated course (Figure 1) or chronic orthopedic complications (Figure 2) included: older age, tibia involvement, infection due to S. aureus/MRSA, presence of multifocal or disseminated infection, DVT, fever > 48 hours of antibiotic therapy, admission laboratory values including higher absolute neutrophil count (ANC) and higher CRP, ICU admission, associated suppurative arthritis, bacteremia, bone abscess, surgical debridement and delayed source control. Conclusion In children with AHO, risk factors for acute and chronic complications are highly similar. Older age, tibia involvement, MRSA, higher ANC and bacteremia were linked to complications in our population and will be assessed in current clinical scoring systems which may help guide management. Disclosures Jonathon C. McNeil, MD, Agency for Healthcare Research and Quality: Grant/Research Support|Allergan: Provided reagents for unrelated research|Nabriva: Site investigator for multicenter clinical trial Kristina G. Hulten, PhD, Me-med: Grant/Research Support|Pfizer: Grant/Research Support Sheldon L. Kaplan, MD, MeMed: Grant/Research Support|Pfizer: Grant/Research Support.

WHAT IS GOOD FOR THE GOOSE IS GOOD FOR THE GARDNER: RARE CASE OF SEVERE SEPSIS AND ORGAN FAILURE DUE TO GARDNERELLA VAGINALIS INFECTION IN A HEALTHY MALE PATIENT

WHAT IS GOOD FOR THE GOOSE IS GOOD FOR THE GARDNER: RARE CASE OF SEVERE SEPSIS AND ORGAN FAILURE DUE TO GARDNERELLA VAGINALIS INFECTION IN A HEALTHY MALE PATIENT

1298. Validation of Local Pseudomonas aeruginosa Risk Factors in Patients with Community-Onset Bacterial Pneumonia

BackgroundClinical guidelines for community-acquired pneumonia (CAP) encourage validation of local risk factors for multidrug-resistant organisms. This study aimed to validate previously derived, local risk factors for Pseudomonas aeruginosa in patients with community-onset bacterial pneumonia at Prisma Health-Midlands’ hospitals. MethodsIn this retrospective, observational cohort study, adult patients hospitalized with pneumonia MS-DRG codes from January 1, 2017 to March 31, 2020 were randomly screened. Enrolled subjects were admitted to 1 of 3 Prisma Health-Midlands’ hospitals with: diagnosis of pneumonia; receipt of inpatient antibiotics within 48 hours of symptom onset; receipt of over 48 hours of antibiotic therapy; and a causative bacterial pathogen identified via respiratory or blood culture, urinary antigen, or respiratory multiplex PCR panel. Performance of the locally derived score was compared to the Drug Resistance in Pneumonia (DRIP) Score, IDSA 2019 CAP guideline risk factors, and healthcare-associated pneumonia (HCAP) risk factors. Endpoints included sensitivity, specificity, positive and negative predictive value, overall accuracy, and over- and undertreatment rates. Overall accuracy was defined as a case in which the gram-negative antibiotic coverage recommended by the scoring schema would have been appropriate for the identified organism, i.e. neither overtreatment (overly broad-spectrum) nor undertreatment (inadequate spectrum). ResultsOf 713 patients screened, 36 patients met criteria and were enrolled. The most common bacterial pathogens identified were Pseudomonas aeruginosa (n = 10, 27.8%) and Streptococcus pneumoniae (n = 10, 27.8%). Performance characteristics for each scoring schema are summarized in Table 1.Table 1. Performance characteristics of risk scores predicting for Pseudomonas aeruginosa community-onset bacterial pneumonia. MDRO=multidrug-resistant organism; DRIP=Drug Resistance in Pneumonia Score; IDSA=Infectious Diseases Society of America 2019 Community-Acquired Pneumonia Guideline risk factors ; HCAP=healthcare-associated pneumonia risk factorsConclusionCompared to DRIP or IDSA 2019 CAP risk scores, the local risk score performed well at ruling out resistant gram-negatives given its higher specificity and lower overtreatment rate; yet, it did not perform as well at ruling in resistant gram-negatives given a lower sensitivity and undertreatment rate. All scores performed better than HCAP risk factors. Data from this study will be utilized to further refine the local risk score algorithm. Disclosures P. Brandon Bookstaver, Pharm D, ALK Abello, Inc. (Grant/Research Support, Advisor or Review Panel member)Biomerieux (Speaker’s Bureau)Kedrion Biopharma (Grant/Research Support, Advisor or Review Panel member) Hana Winders, PharmD, BCIDP, biomerieux (Grant/Research Support) Julie Ann Justo, PharmD, MS, BCPS-AQ ID, bioMerieux (Speaker’s Bureau)Merck & Co. (Advisor or Review Panel member)Therapeutic Research Center (Speaker’s Bureau)Vaxart (Shareholder)

Real-World Application of a Procalcitonin Monitoring Protocol in a Pediatric Intensive Care Unit.

Procalcitonin (PCT) is a biomarker used as an indicator for inflammation and bacterial infections. In October 2018, our PICU implemented a PCT monitoring protocol incorporating cutoffs established in previous studies to help guide antibiotic decision-making in patients undergoing sepsis evaluation. The study objective was to evaluate adherence to the protocol with regard to PCT monitoring and antibiotic use. This retrospective review included PICU patients with systemic inflammatory response syndrome ages > 1 month to 18 years with at least 1 PCT level and blood culture obtained during the 9 months following protocol implementation. Patients were excluded if they received < 48 hours of antibiotic therapy, were neutropenic, or had antibiotics initiated at another hospital. Patients were evaluated for protocol adherence, defined as antibiotic continuation or discontinuation per protocol guidance without excess PCT monitoring. Descriptive statistics were employed. Out of 100 patients evaluated, 50 patients were included. Full adherence was observed in 17 patients (34%). Reasons for non-adherence were excess PCT monitoring (54.5%), antibiotic continuation (30.3%), or both (15.2%). Of patients who were non-adherent due to antibiotic continuation, 61.5% had a positive respiratory viral panel (RVP). A total of 49 excess PCT levels were drawn, resulting in an additional $2,000 in health care costs and $15,000 in patient charges. Overall, the impact of our PCT monitoring protocol was difficult to evaluate due to non-adherence, but it highlights potential areas of focus for improving PCT monitoring and antimicrobial stewardship, such as inclusion of RVP results.

Effect of Inadequate Empiric Antibacterial Therapy on Hospital Outcomes in SARS-CoV-2-Positive and -Negative US Patients With a Positive Bacterial Culture: A Multicenter Evaluation From March to November 2020.

BackgroundIncreased utilization of antimicrobial therapy has been observed during the coronavirus disease 2019 pandemic. We evaluated hospital outcomes based on the adequacy of antibacterial therapy for bacterial pathogens in US patients.MethodsThis multicenter retrospective study included patients with ≥24 hours of inpatient admission, ≥24 hours of antibiotic therapy, and discharge/death from March to November 2020 at 201 US hospitals in the BD Insights Research Database. Included patients had a test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and a positive bacterial culture (gram-positive or gram-negative). We used generalized linear mixed models to evaluate the impact of inadequate empiric therapy (IET), defined as therapy not active against the identified bacteria or no antimicrobial therapy in the 48 hours following culture, on in-hospital mortality and hospital and intensive care unit length of stay (LOS).ResultsOf 438 888 SARS-CoV-2-tested patients, 39 203 (8.9%) had positive bacterial cultures. Among patients with positive cultures, 9.4% were SARS-CoV-2 positive, 74.4% had a gram-negative pathogen, 25.6% had a gram-positive pathogen, and 44.1% received IET for the bacterial infection. The odds of mortality were 21% higher for IET (odds ratio [OR], 1.21; 95% CI, 1.10–1.33; P < .001) compared with adequate empiric therapy. IET was also associated with increased hospital LOS (LOS, 16.1 days; 95% CI, 15.5–16.7 days; vs LOS, 14.5 days; 95% CI, 13.9–15.1 days; P < .001). Both mortality and hospital LOS findings remained consistent for SARS-CoV-2-positive and -negative patients.ConclusionsBacterial pathogens continue to play an important role in hospital outcomes during the pandemic. Adequate and timely therapeutic management may help ensure better outcomes.

Comparison of Narrow-Versus Broad-Spectrum Antibiotics in Elderly Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease

Background Little evidence is available regarding the choice of empiric antibiotic therapy in elderly patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The primary objective of this study is to compare the outcomes of elderly patients receiving broad- versus narrow-spectrum antibiotics during hospitalization for AECOPD. Design A multicenter, retrospective, cohort analysis was performed. Inpatients 65 years and older with a primary discharge diagnosis of AECOPD who received ≥48 hours of antibiotic therapy were included in the study population. Patients were compared based on the spectrum of their antibiotic therapy. Narrow-spectrum antibiotics included: azithromycin, doxycycline, sulfamethoxazole/trimethoprim, or aminopenicillin. The primary outcome was a composite of mechanical ventilation 48 hours after admission, transfer to the intensive care unit 48 hours after admission, 30-day chronic obstructive pulmonary disease (COPD) readmission, and oxygen saturation less than 90% on room air or increased oxygen requirements from baseline 48 hours after admission. Results Two hundred fifty-three patients were included in this analysis; 127 patients were included in the narrow-spectrum group, and 126 patients were included in the broad-spectrum group. Patient demographics and comorbid conditions were similarly distributed in each group. The incidence of the primary composite outcome occurred in 50 (39.3%) and 60 (47.6%) of patients in the narrow- and broad-spectrum groups, respectively (P = .19). Conclusions and Relevance No difference was found in the primary outcome in inpatients aged ≥65 years with AECOPD who received empiric broad-spectrum or narrow-spectrum antibiotics.

1001. Evaluation of the Clinical Efficacy and Safety of Oral Antibiotic Therapy for Streptococcus spp. Bloodstream Infections

BackgroundDespite the severity and frequency of bloodstream infections (BSI), the effectiveness of oral definitive therapy remains unknown. The objective of this study was to evaluate the efficacy and safety of step down oral antibiotics for the treatment of Streptococcus spp. BSI.MethodsThis was a retrospective cohort study of adult, hospitalized patients with Streptococcus spp. BSI between June 2015 and June 2017. Patients were excluded if received <48 hours of antibiotic therapy or therapy was started >48 hours from first positive culture. Patients were grouped by receipt of step down oral antibiotic therapy (PO group) vs. full course IV therapy (IV group) and compared for demographics, clinical course, and outcomes. The primary outcome was 30-day mortality and hospital length of stay (LOS). The secondary outcomes included 30-day recurrence of BSI and adverse events (AEs).ResultsOne hundred ninety-five patients met inclusion criteria; median age was 51 year old, 68% were male, 57% were Hispanic, and 71% had community-onset BSI. Sixty-four (33%) were treated with step down oral therapy. The most common source of bacteremia was pneumonia (21%); 8% had endocarditis. Comorbidities were similar between the groups, with diabetes being most common (IV 22% vs. PO 19%, P = 0.29). Severity of illness measured by need for ICU admission, initial lactate level, and SOFA score was similar between the two groups. S. viridans was the most frequent pathogen isolated (IV 28% vs. PO 27%, P = 0.87). Ceftriaxone (39%) for the IV group and levofloxacin (30%) for the PO group were the most common definitive therapy prescribed. PO group received 4 days of IV therapy prior to transition to orals. The IV group had significantly higher mortality rate (11% vs. 2%, P = 0.02) and longer LOS (median 9 days [IQR 5–18] vs. 5 days [4–7.75], P ≤ 0.01) compared with the PO group. 30-day recurrence (IV 2% vs. PO 5%, P = 0.40) and AEs (IV 2% vs. PO 3%, P = 0.60) were similar between the two groups.ConclusionIn Streptococcus spp. BSI, step down oral antibiotic therapy was associated with a significantly shorter LOS compared with IV only therapy without compromise of clinical outcomes. Larger prospective trials evaluating step down oral therapy are warranted to confirm our results.Disclosures All authors: No reported disclosures.

Adjunctive rifampicin to reduce early mortality from Staphylococcus aureus bacteraemia: the ARREST RCT.

Staphylococcus aureus bacteraemia is a common and frequently fatal infection. Adjunctive rifampicin may enhance early S. aureus killing, sterilise infected foci and blood faster, and thereby reduce the risk of dissemination, metastatic infection and death. To determine whether or not adjunctive rifampicin reduces bacteriological (microbiologically confirmed) failure/recurrence or death through 12 weeks from randomisation. Secondary objectives included evaluating the impact of rifampicin on all-cause mortality, clinically defined failure/recurrence or death, toxicity, resistance emergence, and duration of bacteraemia; and assessing the cost-effectiveness of rifampicin. Parallel-group, randomised (1 : 1), blinded, placebo-controlled multicentre trial. UK NHS trust hospitals. Adult inpatients (≥ 18 years) with meticillin-resistant or susceptible S. aureus grown from one or more blood cultures, who had received < 96 hours of antibiotic therapy for the current infection, and without contraindications to rifampicin. Adjunctive rifampicin (600-900 mg/day, oral or intravenous) or placebo for 14 days in addition to standard antibiotic therapy. Investigators and patients were blinded to trial treatment. Follow-up was for 12 weeks (assessments at 3, 7, 10 and 14 days, weekly until discharge and final assessment at 12 weeks post randomisation). The primary outcome was all-cause bacteriological (microbiologically confirmed) failure/recurrence or death through 12 weeks from randomisation. Between December 2012 and October 2016, 758 eligible participants from 29 UK hospitals were randomised: 370 to rifampicin and 388 to placebo. The median age was 65 years [interquartile range (IQR) 50-76 years]. A total of 485 (64.0%) infections were community acquired and 132 (17.4%) were nosocomial; 47 (6.2%) were caused by meticillin-resistant S. aureus. A total of 301 (39.7%) participants had an initial deep infection focus. Standard antibiotics were given for a median of 29 days (IQR 18-45 days) and 619 (81.7%) participants received flucloxacillin. By 12 weeks, 62 out of 370 (16.8%) patients taking rifampicin versus 71 out of 388 (18.3%) participants taking the placebo experienced bacteriological (microbiologically confirmed) failure/recurrence or died [absolute risk difference -1.4%, 95% confidence interval (CI) -7.0% to 4.3%; hazard ratio 0.96, 95% CI 0.68 to 1.35; p = 0.81]. There were 4 (1.1%) and 5 (1.3%) bacteriological failures (p = 0.82) in the rifampicin and placebo groups, respectively. There were 3 (0.8%) versus 16 (4.1%) bacteriological recurrences (p = 0.01), and 55 (14.9%) versus 50 (12.9%) deaths without bacteriological failure/recurrence (p = 0.30) in the rifampicin and placebo groups, respectively. Over 12 weeks, there was no evidence of differences in clinically defined failure/recurrence/death (p = 0.84), all-cause mortality (p = 0.60), serious (p = 0.17) or grade 3/4 (p = 0.36) adverse events (AEs). However, 63 (17.0%) participants in the rifampicin group versus 39 (10.1%) participants in the placebo group experienced antibiotic or trial drug-modifying AEs (p = 0.004), and 24 (6.5%) participants in the rifampicin group versus 6 (1.5%) participants in the placebo group experienced drug-interactions (p = 0.0005). Evaluation of the costs and health-related quality-of-life impacts revealed that an episode of S. aureus bacteraemia costs an average of £12,197 over 12 weeks. Rifampicin was estimated to save 10% of episode costs (p = 0.14). After adjustment, the effect of rifampicin on total quality-adjusted life-years (QALYs) was positive (0.004 QALYs), but not statistically significant (standard error 0.004 QALYs). Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S. aureus bacteraemia. Given the substantial mortality, other antibiotic combinations or improved source management should be investigated. Current Controlled Trials ISRCTN37666216, EudraCT 2012-000344-10 and Clinical Trials Authorisation 00316/0243/001. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 59. See the NIHR Journals Library website for further project information.

Acute Exacerbations of Chronic Obstructive Pulmonary Disease With a Low Procalcitonin Concentration: Impact of Antibiotic Therapy

Patients admitted with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) often are prescribed antibiotics. Studies have shown that the use of procalcitonin (PCT) to guide the decision to initiate antibiotic therapy in AECOPD has resulted in less antibiotic use and similar outcomes compared with standard of care. We evaluated patients with AECOPD and low PCT concentrations to determine whether antibiotic therapy was associated with improved outcomes. We retrospectively evaluated adult patients admitted with AECOPD who had a peak PCT concentration <0.25 µg/mL. Patients were evaluated based on their antibiotic exposure: ≤24 hours vs >24 hours. We also evaluated outcomes based upon the duration of azithromycin therapy: ≤24 hours vs >24 hours. The primary outcome was all-cause 30-day readmissions. Secondary outcomes included length of stay (LOS) and COPD-related 30-day readmissions. One hundred sixty-one and 195 patients received ≤24 hours vs >24 hours of antibiotic therapy, respectively. The cohort with ≤24 hours of antibiotics had a shorter LOS (2.8 vs 3.7 days; P = .01). There were no differences in all-cause 30-day readmissions (15.5% vs 17.4%; P = .63) or COPD-related 30-day readmissions (11.2% vs 12.3%; P = .74). Additionally, patients receiving ≤24 hours of azithromycin had a shorter LOS (3.0 vs 3.8 days; P = .002) and there were no differences in all-cause 30-day readmissions (16.2% vs 17.1%; P = .82) or COPD-related 30-day readmissions (11.9% vs 11.6%; P = .94). For adult patients hospitalized with nonsevere AECOPD and low PCT concentrations, antibiotic therapy beyond 24 hours did not improve outcomes.

Following the (Clinical Decision) Rules: Opportunities for Improving Safety and Resource Utilization With the Bacterial Meningitis Score.

The Bacterial Meningitis Score accurately classifies children with cerebrospinal fluid (CSF) pleocytosis at very low risk (VLR) versus not very low risk (non-VLR) for bacterial meningitis. Most children with CSF pleocytosis detected during emergency department evaluation are hospitalized despite the high accuracy of this prediction rule and the decreasing incidence of bacterial meningitis. The lack of widespread use of this rule may contribute to unnecessary risk exposure and costs. This cross-sectional study included 1049 patients who, between January 2010 and May 2013, had suspicion for meningitis and underwent both a complete blood cell count and CSF studies during their emergency department evaluation. We then examined their hospitalizations to characterize exposure to drugs, radiologic studies, and the costs associated with their care to determine the safety and value repercussions of these VLR admissions. Primary outcomes include duration of antibiotics, exposure to drugs and radiology studies, safety events, and costs incurred during these VLR admissions. Twenty patients classified as VLR were admitted to the hospital. On average they received 35 hours of antibiotic therapy. There was 1 adverse drug event and 1 safety event. The VLR patients admitted to the hospital were exposed to risk and costs despite their low risk stratification. Systematic application of the Bacterial Meningitis Score could prevent these exposures and costs.

Antibiotics Before Removal of Percutaneously Inserted Central Venous Catheters Reduces Clinical Sepsis in Premature Infants.

Evaluate the incidence of postcatheter removal clinical sepsis when antibiotics were infused prior to the removal of percutaneously inserted central venous catheters (PICCs). A retrospective chart review of premature neonates (n = 196) weighing ≤1250 g at birth with 218 PICC line removals in the presence or absence of antibiotics at a tertiary level neonatal intensive care unit (NICU) between January 1, 2010, and May 31, 2012. Charts were reviewed looking for the presence of clinical sepsis defined as a sepsis workup including white blood cell count, differential, C-reactive protein, blood and/or cerebral spinal fluid (CSF), and urine cultures along with at least 48 hours of antibiotic therapy given within 72 hours after removal of a PICC line. Antibiotics were considered present at line removal if given within 12 hours before catheter removal either electively or at completion of a planned course. When antibiotics were given within 12 hours before PICC line removal, only 2% of the line removal episodes (1/48) resulted in a neonate developing clinical sepsis versus 13% (21/165) when no antibiotics were given prior to removal (p = 0.03, Fisher's exact test). Despite the increased use of elective antibiotics with line removal, there was no increase in total antibiotic usage due to the overall decrease in episodes of clinical sepsis or changes in antibiogram susceptibility patterns. There was an 11% absolute decrease and a 6-fold relative decrease in postcatheter removal clinical sepsis events in premature neonates who received antibiotics prior to PICC line removal.

Management of Early Pregnancy Failure in a Patient with Pancytopenia

The safest and most effective therapy for an early pregnancy failure in women with pancytopenia is unknown. Here, we present a case report of a patient diagnosed with a 10-week embryonic demise who had a rare hematologic disorder called TnPolyagglutination syndrome that caused pancytopenia. The patient was offered expectant, medical, or surgical management, and she chose outpatient vaginal misoprostol. A week later, the patient presented to the emergency room with a septic abortion. She was given broad spectrum antibiotics and a suction dilation & curettage was performed. After 72 hours of antibiotic therapy, the patient was discharged home and made a full recovery to baseline. This case suggests that initial surgical management of early pregnancy failure in women with pancytopenia should be considered and strongly recommended over expectant or medical management. We review management options and surgical planning for patients with pancytopenia, regardless of the etiology.

Glycerol and Acetaminophen as Adjuvant Therapy Did Not Affect the Outcome of Bacterial Meningitis in Malawian Children

We investigated the benefit of 2 candidate adjunctive therapies in bacterial meningitis: glycerol, which has shown promise in earlier studies, and acetaminophen, which is reportedly beneficial in adult septicemia. In a hospital in Blantyre, Malawi, we enrolled 360 children aged ≥ 2 months with proven bacterial meningitis (36% HIV infected) in a double-blind, randomized, placebo-controlled trial of glycerol and acetaminophen in a 2 × 2 factorial design. Of 4 groups, first group received oral glycerol, second received rectal acetaminophen, third received both therapies and the fourth received placebos only. Adjuvant therapies were given for the first 48 hours of antibiotic therapy. Endpoints were mortality and neurological sequelae. Baseline findings were similar across all groups, except that many children had prior antibiotics in the acetaminophen group and many were anemic in the acetaminophen and glycerol group. Outcomes were similar for all groups. We found no benefit from oral glycerol or rectal acetaminophen in, mostly pneumococcal, meningitis in Malawian children.

Herpes Simplex Virus Infection in Neonates and Young Infants with Sepsis

Background:Neonatal herpes infection is the most serious complication of Herpes Simplex Virus (HSV) infection during pregnancy and perinatal period. Few studies have reported neonatal HSV infection in developing countries.Objectives:The aim of this study was to detect the HSV infection among neonates and infants with sepsis.Materials and Methods:In a cross sectional study all infants aged less than 3 months, admitted to neonatal intensive care unit and pediatric emergency ward of Ghaem Hospital (a university hospital with 900 beds) in Mashhad (Northeast of Iran) with clinical diagnosis of sepsis and at least one inclusion criteria during one year from November 2009 to October 2010, were enrolled in the study. Polymerase chain reaction (PCR) was done on clinical samples obtained from patients.Results:Among 150 neonates and infants younger than 3 months old with sepsis, the PCR results for detecting the HSV DNA, were positive in 6 samples of 5 patients (3.3 %). None of the mothers had symptomatic HSV infection during delivery. The mean age of the patients was 18 days. Two of them died due to shock and disseminated intravascular coagulation (DIC).Conclusions:In neonates and infants with primary diagnosis of sepsis, HSV infection should be considered especially if the clinical condition does not improve after 48 hours of antibiotic therapy, and sepsis still exists with elevated liver enzymes.

Enterovirus Meningitis With Marked Pleocytosis

In neonates and young infants, it can be difficult to distinguish bacterial from aseptic meningitis, especially in the setting of marked CSF (cere-brospinal fluid) pleocytosis. This case series and review of the literature explores the role of early CSF EV-PCR (enterovirus-polymerase chain reaction) in these patients' diagnostic workup, management, and overall hospital stay. Patient 1 was a 30-day-old female who presented with a fever of 102°F and increased irritability for 1 day. She was admitted to the hospital for an evaluation including complete blood cell count (CBC), blood culture, urine culture, urinalysis, and lumbar puncture (LP). Ampicillin, gentamicin, and acyclovir were initiated. Admission laboratory data included peripheral white blood cell (WBC) count of 9200 cells/μL and a normal urinalysis. Cerebrospinal fluid (CSF) was remarkable for pleocytosis of 1005 cells/μL with 53% lymphocytes, 0 red blood cells (RBCs), protein of 92.8 mg/dL, and glucose of 44 mg/dL (Table 1). Gram-stain of the CSF revealed Gram-positive cocci in pairs; however, no bacteria were cultured. Results of the urine culture were negative. The blood culture grew coagulase-negative Staphylococcus, which was believed to be a contaminant. The patient continued to be febrile despite 72 hours of antibiotic therapy. Therefore, a repeat LP was performed, revealing 80 WBC/μL with 63% lymphocytes, 700 RBC/μL, protein of 138 mg/dL, and glucose of 38 mg/dL. Enterovirus-polymerase chain reaction (EV-PCR) performed on the repeat CSF was positive. Herpes simplex virus polymerase chain reaction (PCR) was negative. Antibiotic therapy was discontinued, and the patient was discharged from the hospital. View this table: TABLE 1 Summary of Patient Laboratory Data Patient 2 was a 7-day-old female who presented with fever of 104°F for 1 day and jaundice. She was transferred from a referring hospital after undergoing an evaluation that included CBC, blood culture, urine culture, urinalysis, and LP. Ampicillin, gentamicin, and acyclovir were begun before patient …

Disseminated cryptococcus presenting as cellulitis in a liver transplant recipient

CASE REPORT A 57­year­old African–American male presented to our hospital with a one week history of progressive right lower extremity pain and swelling, associated with fevers, chills and night sweats. Review of systems revealed a one week history of dry cough and right­sided pleuritic chest pain. He received an orthotopic liver transplant four months earlier at our institution for end stage liver disease and cirrhosis secondary to Hepatitis C. After transplantation, his maintenance immunosuppressive regimen included tacrolimus (2 mg every morning, 1 mg every evening), and mycophenolate mofetil (1000 mg twice daily). On admission, he was afebrile. His right lower extremity was exquisitely tender to palpation; erythema, warmth and 2+ pitting edema were also noted (Figure 1). No nodules, ulcers, pustules or papules were noted on the lower extremities. His white­blood­cell count was 9900 cells per uL, with 85% neutrophils and 2% bands. Radiography of the right lower extremity did not reveal a fracture and an ultrasound did not demonstrate a deep vein thrombosis. Chest X­ray revealed a new nodular density in the right mid­lung. Computed tomography (CT) scan of the chest was obtained and revealed multifocal pneumonia (Figure 2). Vancomycin and cefepime were initiated empirically for suspected bacterial cellulitis and pneumonia. Despite 48 hours of antibiotic therapy, the patient’s symptoms failed to improve. Serum cryptococcal antigen was obtained and the titer was positive at 1:10. A skin biopsy was performed and revealed necrotizing granulomas, with the GMS stain revealing yeasts. Bronchoscopy and transbronchial biopsy also showed yeasts (Figure 3). C. neoformans was subsequently isolated from his bronchoalveolar lavage. Lumbar puncture was performed and the CSF was unremarkable. The patient received liposomal amphotericin B at 3 mg/kg per day for two weeks, during which time tacrolimus dosing was decreased by 50% and mycophenolate mofetil was discontinued. Improvement in cellulitis and pulmonary infiltrates was noted and he transitioned to oral fluconazole. His tacrolimus dosing remained reduced for the first three months of therapy as an outpatient. The patient completed a 12­month course of fluconazole and has not demonstrated relapse to date. DISCUSSION In 2010, the Transplant­Associated Infection Surveillance Network identified Cryptococcus as the 3rd leading cause of invasive fungal infections in solid organ transplant recipients, with an incidence of 8% and a one­year mortality rate of 27% [1]. Although cryptococcal disease has a median onset of greater than one year post­transplantation, this varies with the type of organ transplanted; in the case of liver transplant recipients it is 8.8 months [1, 2]. While the majority of cryptococcal disease among solid organ transplant recipients is disseminated or involves the central nervous system, it may also present with skin, soft tissue or osteoarticular infection [3]. Rates of skin and soft tissue infection have been reported in the range of 13–18% [2, 4]. A variety of manifestations have been reported: nodules, maculopapular lesions, ulcers, pustules, abscesses and cellulitis, with the most common site being the lower CLINICAL IMAGES OPEN ACCESS

Pathogens Implicated in Acute Otitis Media Failures After 7-valent Pneumococcal Conjugate Vaccine Implementation in France

Before 7-valent pneumococcal conjugate vaccine (PCV7) implementation in France, several studies had described the microbiology of acute otitis media (AOM) treatment failures. The causative pathogens were Streptococcus pneumoniae (Sp) followed by nontypable Haemophilus influenzae (NTHi). The aim of this study was to describe the epidemiology of pathogens involved in AOM treatment failures or recurrences. This French multicentric prospective study enrolled 143 children with AOM treatment failure between 2007 and 2009 observed by 8 ear, nose, and throat specialists. Failure was defined as the persistence of AOM symptoms after at least 48 hours of antibiotic therapy or their recurrence within 4 days after the end of treatment. Standardized history and physical examination findings were recorded, and culture of middle ear fluid (MEF) was obtained. Mean age was 16.9 ± 9.9 months (median, 13.7). Eighty-eight percent of children had received more than 1 dose of PCV7, and 70.6% attended day care. The most common antibiotic used at the time of treatment failure or recurrence was a combination of amoxicillin and clavulanate (51.1%). Bacteriologic sampling demonstrated that in 35% of cases (n=50), no otopathogen was cultured at the time of treatment failure or recurrence. Similar proportions of Sp and NTHi were observed in the 86 patients (60.1%) from whom only a single species was recovered from MEF (46.5% for Sp, n=40 and 45.3% for NTHi, n=39). Among Sp strains, 4.4% were penicillin susceptible, 77.8% were penicillin intermediate, and 17.8% were fully penicillin resistant, and serotype 19A represented 84.5% of all serotypes detected. Among NTHi isolates, 15.5% (n=7) were β-lactamase-producing strains (including 2 strains with only this mechanism of resistance), and strains with reduced susceptibility by changes in protein binding to penicillin (β-lactamase-negative ampicillin resistant strains) represented 35.5% of cases. Among the 50 sterile MEF samples, polymerase chain reaction was performed in 32, of which 4 were positive for HI, 3 for Sp, and 3 for both. Among children with AOM treatment failures in France, Sp and NTHi were equally distributed; 19A was the main Sp serotype, and the main resistance mechanism for NTHi was β-lactamase-negative ampicillin resistance.

A guideline for the inpatient care of children with pyelonephritis

BACKGROUND AND OBJECTIVES:Febrile urinary tract infections and pyelonephritis are common in children and frequently lead to hospitalization for management, especially in the child who appears toxic. The American Academy of Pediatrics (AAP) practice parameter on the diagnosis, treatment and evaluation of the initial urinary tract infection in febrile infants and young children provides experience and evidence-based guidelines for the practitioner caring for children between the ages of 2 months to 2 years. No established guideline exists for older children and the AAP guideline does not specifically focus on inpatient care.METHODS:We conducted a comprehensive review of recently published literature and practice guidelines to develop a consensus on the inpatient diagnosis and management of children with pyelonephritis.RESULTS:Eight recommendations are proposed for the diagnosis and management, including revised guidelines for the imaging studies postpyelonephritis on the basis of current best evidence.CONCLUSION:Proper diagnosis of pyelonephritis, timely initiation of appropriate therapy and identification of children at risk for renal injury will help to reduce immediate as well as long-term complications due to chronic kidney disease.

Acute Q fever in hospitalised patients in Central Tunisia: report of 21 cases

Q fever is caused by Coxiella burnetii, which is an obligate intracellular bacterium. In Tunisia, although the prevalence of Q fever among blood donors is high (26%) [1Letaief AO Yacoub S Dupont HT et al.Seroepidemiological survey of rickettsial infections among blood donors in central Tunisia.Trans R Soc Trop Med Hyg. 1995; 89: 266-268Abstract Full Text PDF PubMed Scopus (55) Google Scholar], this disease is rarely diagnosed. The aim of this study was to describe epidemiological and clinical features of acute Q fever in adults in central Tunisia. We included all patients diagnosed with acute Q fever, hospitalised in the Infectious Diseases Unit of a tertiary teaching hospital in Sousse, between January 2003 and December 2007. Epidemiological, clinical and laboratory data were recorded from the medical charts. Eight patients had serology performed by immunofluorescence assay (IFA), in the Department of Microbiology in our hospital, to detect IgG antibodies against C burnetii (without specifying antigen phase), and 13 patients had serology performed in the Unité; des Rickettsies, Faculté de Médecine de Marseille–France, to detect IgG and IgM antibodies (anti-phase I and phase II C. burnetii). Moreover, sera of all patients were tested for the presence of Rickettsia conorii antibodies. Diagnosis of acute Q fever was established in the presence of IgG titre >1/80 and IgM >1/50, or seroconversion or a four-fold or higher rise in IgG titres. Twenty-one patients, 13 males and eight females, mean age = 40 years old (range, 16–65), were hospitalised for acute Q fever. Nineteen cases (90.5%) occurred between May and September. Rural origin and contact with pets were found in 11 patients (52.3%). Fifteen patients (71.5%) had hepatitis, five (23.5%) had pneumonia and three (14.5%) had a flu-like syndrome. Two patients had associated hepatitis and pneumonia. The most common symptoms were fever (100%), fatigue (76%) and chills (47.5%). Skin rash was present in five patients (23.5%) (Table 1). Meningitis was suspected in two cases and confirmed in one patient; lumbar puncture showed lymphocytic meningitis and normal glucose level in cerebrospinal fluid. The most common laboratory findings were: normal WBC count or leucopenia, cytolysis (15 cases = 71.5% each), and thrombopenia (12 cases = 57%); one patient had renal failure. Six patients had serological evidence of concomitant or previous infection with spotted fever group rickettsioses (SFGR).TABLE 1Clinical data of patients with acute Q feverClinical featuresNumber of cases (%)Fever21 (100)Fatigue/arthromyalgia16 (76.1)Chills10 (47.5)Headache9 (42.8)Sweats7 (33.3)Gastrointestinal symptoms6 (28.5)Cough/lung crepitations3 (14.3)Neck stiffness2 (9.5) Open table in a new tab Sixteen patients (76.1%) were treated with antibiotics, 14 (87.5%) with doxycycline, for a mean duration of 14 days (range, 5–21). Apyrexia was obtained within a mean duration of 36 hours of antibiotic therapy (range, 24–72). The outcome was favourable in all the cases. In 2004, 8% of the patients hospitalised in our department for acute fever of undetermined origin had acute Q fever [2Kaabia N Rolain JM Khalifa M et al.Serologic study of rickettsioses among acute febrile patients in central Tunisia.Ann N Y Acad Sci. 2006; 1078: 176-179Crossref PubMed Scopus (21) Google Scholar]. However, it is usually misdiagnosed because of its clinical polymorphism and only tertiary teaching hospitals’ laboratories can provide C. burnetii serology. In our series, hepatitis was the most common clinical pattern (71.5%), as was described in a French series [3Raoult D Dupont HT Foucault C et al.Q fever 1985-1998. Clinical and epidemiologic features of 1,383 infections.Medicine. 2000; 79: 109-123Crossref PubMed Scopus (462) Google Scholar]. However, pneumonia predominates in Spain [4Sampere M Font B Font J Sanfeliu I Segura F Q fever in adults: review of 66 clinical cases.Eur J Clin Microbiol Infect Dis. 2003; 22: 108-110PubMed Google Scholar]. This diversity of clinical presentations could be explained by either a difference in route of infection or variations in the strains of C. burnetii. In our series, concomittent or previous Q fever and SFGR was noted in six patients. This situation has been reported in five cases in the literature; it could be explained by dual infections or co-transmission of aetiological agents by tick bites [5Rolain JM Gouriet F Brouqui P et al.Concomitant or consecutive infection with Coxiella burnettii and Rickettsia conorii.CID. 2005; 40: 82-88Crossref PubMed Scopus (58) Google Scholar]. In our region, acute Q fever should be considered in any febrile patient with hepatitis or atypical pneumonia who may have had contact with infected animals. More epidemiological studies, especially in immunocompromised patients and pregnant women, are needed.

Index of Suspicion in the Nursery

Index of Suspicion in the Nursery