Culture Confirmation Research Articles

Microbiology and Epidemiology of Orbital Cellulitis in Pediatric and Young Adult Patients.

Using data from the large and geographically diverse Military Health System (MHS) beneficiary population, we aimed to characterize and update the epidemiology and microbiology of pediatric orbital cellulitis given previous data are limited to small, single-center studies. Following institutional review board approval, we performed a retrospective analysis using the Military Health System admissions, microbiology, and pharmacy data between June 2009 and September 2019. Patients less than 22 years of age with radiological confirmation of orbital cellulitis were included. Demographic data, presence of sinusitis, advanced imaging reports, blood and wound culture results with antibiotic susceptibilities, and antibiotic prescriptions were collected. Descriptive statistics were used to summarize demographic characteristics. Imaging findings were grouped by Chandler's stage (CS), an imaging-based measure of the progressive severity of orbital involvement. A Cochran-Armitage trend test was used to evaluate the relationship between CS and likelihood of positive confirmatory culture. There was a male predominance (66.9%) and 55.5% of subjects had comorbid sinusitis. Of the 130 subjects included, 33.8% had one or more positive cultures, 30.8% had a positive wound culture, and 4.6% had a positive blood culture. The most identified organism was coagulase-negative staphylococci (23.3%), followed by Staphylococcus aureus (18.9%), Streptococcus intermedius (17.8%), and strict anaerobes as a group (13.3%). Gram-negative organisms were rare. Twenty-five percent of S. aureus were methicillin-resistant. Clindamycin resistance was identified in 9% of all S. aureus, 50% of coagulase-negative staphylococci, and 25% of S. intermedius. Clindamycin plus ceftriaxone was the most prescribed empiric antibiotic regimen (36.2%). Likelihood of a positive culture significantly increased with advancing CS. Orbital cellulitis occurs most frequently in males with sinusitis. Likelihood of positive wound culture is increased with a more advanced CS. Staphylococcus and Streptococcus spp. and anaerobes are the most identified pathogens in orbital cellulitis, while gram-negative organisms are rare. Empiric antibiotic selection should include an anti-methicillin-resistant S. aureus agent combined with a broad-spectrum beta-lactam and anaerobic coverage.

Monitoring microbial safety and evaluation of removal efficiency from drinking water in Ahvaz, Iran

The availability of potable water sources is vital worldwide. Due to the potential for microbial contamination, developing nations focus more research on the existence of microorganisms that are indicators in water than they do on chemical presence. This study was done in order to assess the microbial level of drinking water in Ahvaz city. In this descriptive-cross-sectional study, the measure the microbial tests, two culture mediums, MacConkey broth, and green lactose broth, were used for possible and confirmatory culture respectively. Bioindicators measured in drinking water included fecal coliform and total coliform. Not only the residual chlorine concentration was also measured, but its relationship with bioindicators was also calculated by Spearman's correlation test. Result of this study showed that, the maximum total coliform concentration reported is between 2021 and 2022 (1600 MPN/100 ml). Based on result of this study the average concentration of fecal coliform in 2019, 2020, 2021, and 2022 were 11.88, 10.66, 7.78, and 6.11 MPN/100 ml respectively. The average annual concentration of total coliform and fecal coliform in four years was 28.95 and 9.32 MPN/100 ml, respectively. According result of this study, the Karun River, Ahvaz's main drinking water source, is contaminated by surface water runoff, old facilities, and unfiltered discharge of different wastewater kinds from factories, farms, and communities in Khuzestan.

The NICU Antibiotics and Outcomes (NANO) trial: a randomized multicenter clinical trial assessing empiric antibiotics and clinical outcomes in newborn preterm infants

BackgroundEarly-onset sepsis is an important cause of neonatal morbidity and mortality in the preterm population. Infants perceived to be at increased risk for early-onset sepsis are often treated empirically with broad-spectrum antibiotics while awaiting confirmatory blood cultures, despite an overall incidence of early-onset sepsis of 2–3% among extremely-low-birthweight (ELBW) infants. Recent observational studies associate perinatal antibiotic use with an increased incidence of necrotizing enterocolitis, late-onset sepsis, and mortality among ELBW infants. Given currently available data and variability in clinical practice, we designed a prospective multi-institutional randomized controlled trial to determine the safety of early antibiotic use in ELBW infants.MethodsThe NICU Antibiotics and Outcomes (NANO) trial is a multicenter, double-blinded, randomized controlled trial. A sample of 802 ELBW preterm infants will undergo web-based stratified block randomization to receive empiric antibiotics (EA; ampicillin and gentamicin) or placebo during routine evaluation for early-onset sepsis. Participating sites will use preexisting institutional protocols for antibiotic dosage and duration. Infants born at participating sites with a gestational age of 29 weeks or less are eligible for enrollment. Exclusion criteria include maternal intrauterine infection, hemodynamic or respiratory instability, delivery by caesarean section for maternal indications without labor or prolonged rupture of membranes, and prior administration of antibiotics. The primary outcome is the composite incidence of necrotizing enterocolitis, late-onset sepsis, or death during participants’ index hospitalization. Maternal and infant samples will be collected longitudinally and assessed for differences in microbiome composition and diversity.DiscussionThe NANO trial is designed to compare the rate of adverse outcomes of EA use at birth versus placebo in ELBW preterm infants. If EA at birth worsens clinical outcomes, then the results of the trial may help providers decrease antibiotic utilization in the NICU and subsequently decrease the incidence of complications associated with early antibiotic use in ELBW infants. If we instead find that EA improve outcomes, then the trial will validate a longstanding clinical practice that has not previously been supported by high-quality data. Future studies will assess long-term clinical and microbial outcomes in infants who received empiric antibiotics following delivery.Trial registrationTrial registration data: June 25, 2019 NCT03997266.

The Impact of Point-of-Care Polymerase Chain Reaction Testing on Prescribing Practices in Primary Care for Management of Strep A: A Retrospective Before-After Study.

BackgroundRapid antigen detection tests (RADTs) are the standard of care (SOC) for testing in patients with suspected group A β-hemolytic Streptococcus (Strep A) infection. Due to lower sensitivity, guidelines recommend confirmatory microbiological culture following negative RADT results. This process is time-consuming, and adherence is often poor, resulting in high rates of inappropriate antibiotic prescribing. We sought to evaluate the impact of switching from RADTs to point-of-care (POC) polymerase chain reaction (PCR) testing on use of antibiotics in primary care, when used as part of an antibiotic stewardship initiative.MethodsIn this retrospective before–after study, electronic medical records of any patients presenting with suspected acute pharyngitis (June 2018–May 2019) across 15 outpatient primary care clinics were evaluated. Strep A was detected using the cobas Strep A assay (cobas Liat system).ResultsAnalysis of 10 081 eligible patient records showed that POC PCR testing resulted in a 44.1% reduction in antibiotic prescribing for patients with a negative POC PCR test result (10.1% PCR vs 18.0% RADT; P < .0001). Rates of antibiotic prescription varied across clinical sites, ranging between 10.7% and 33.8% and 12.4% and 34.4% during the use of PCR tests and RADTs, respectively. POC PCR had no impact on prescription rates in patients with positive POC test results compared to RADTs (76.2% vs 76.5%, respectively). More than 99% of antibiotics were prescribed during the initial primary care encounter.ConclusionsAs part of a broader antibiotic stewardship initiative, implementation of POC PCR as SOC in outpatients with acute pharyngitis symptoms reduced the volume of inappropriate antibiotic prescriptions.

648. Rapid, Non-invasive Detection of Cryptic Tularemia Using a Plasma-Based Microbial Cell-Free DNA Next-Generation Sequencing Test

Abstract Background Francisella tularensis causes severe infections and is a Category A potential bioterrorism agent but its microbiological diagnosis can be challenging. The diagnosis of tularemia is limited by non-specific protean clinical symptoms that overlap with other infectious syndromes, the fastidious nature of Francisella tularensis, along with insensitivity and poor specificity of serology. Rapid, non-invasive diagnosis of tularemia by microbial cell-free DNA (mcfDNA) next-generation sequencing (NGS) of plasma offers a means to overcome these limitations. Methods The Karius Test™ (KT) detects and quantifies mcfDNA in molecules/µL (MPM) from &amp;gt;1400 organisms in plasma (performed at the CLIA certified/CAP accredited Karius laboratory). KT detections of Francisella tularensis were compiled from three medical centers with clinical review by healthcare providers. Results KT detected Francisella tularensis in four patients. All were adult males in whom the diagnosis was unexpected. The most common symptoms were fever and chest pain. White blood cell count neutrophilic predominance and abnormal chest X-ray findings were found in three cases. A broad infectious disease work-up was performed with the initiation of broad spectrum empiric antibiotics in all cases. KT was the first test to identify Francisella tularensis as the microbiological diagnosis with a time to diagnosis of 2.25 days (avg) +/- 0.5 from sample collection (one day from sample receipt in all cases), enabling narrowed, targeted antibiotic treatment. Francisella tularensis mcfDNA concentration was 1772 MPM (avg) +/- 1914. KT was the only test to establish the diagnosis in two cases; tularemia serologies were confirmatory in two cases, one of which had confirmatory culture from lymph node biopsy. Three patients were diagnosed with the pneumonic form of the illness and one with a visceral glandular form. Possible epidemiological exposures were identified in all cases. Conclusion KT enabled rapid, non-invasive, plasma-based diagnosis of diverse clinical manifestations of invasive tularemia against a competing broad infectious and non-infectious differential diagnosis. Timely diagnosis enabled targeted narrowing of antibiotic therapy and successful treatment of pneumonic and glandular forms of the infection. Disclosures All Authors: No reported disclosures

Cholera Outbreak in Hadhramout, Yemen: The Epidemiological Weeks 2019

Background and aims: Cholera is a disease of acute watery diarrhea caused by Vibrio cholerae usually transmitted through contaminated water. In this study, we collected and analyzed the related epidemiological data to determine cholera outbreak in Hadhramout, Yemen during the disease epidemic in 2019. Methods: A cross-sectional study was conducted according to screening rapid diagnostic and confirmatory laboratory culture testing methods for diagnosing clinically cholera cases. Results: Suspected cholera cases were tested by rapid diagnostic test (RDT) and 399 (50.5%) out of 794 cases were determined positive, and 76(9.6%) of them were confirmed by laboratory culture test (LCT) with statistically significant difference. Serotype V. cholerae O1 was also detected in patients’ diarrhea. Females were the most affected by the disease manifested in 201 (25.3%) and 43 (5.4%) when tested by RDT and LCT, respectively, with no statistically significant difference. The highest proportion of cholera cases (224) were reported in the age group less than 15 years (56.1%) with statistically significant difference when tested by RDT, and 45(13.3%) when tested by LCT with insignificant statistics difference. Hajr directorate was revealed to be the most affected with 242 (30.47%) followed by Mukalla city directorate with 108 (13.60%) when the cases were tested by RDT; while Hajr and Mukalla city directorates reported 55 (7.0%) and 15 (2.0%), respectively, when it was confirmed by LCT with a statistically significant difference. Conclusion: Severe cholera outbreak occurred during the epidemiological weeks in 2019 in Hadhramout coast. V. cholerae O1 serotype was the causative agent of cholera. Females and age group less than 15 years were the most affected by the disease. Hajr and Mukalla city directorates reported serious outbreak cholera cases.

Use of the BioFire Film Array Blood Culture Identification(BCID) Panel(BioFire Diagnostics, Salt Lake City, Utah) on Pleural Fluid Samples in Pediatric Patients Hospitalized for Community Acquired Pneumonia(CAP)

Abstract Introduction/Objective CAP accounts for approximately 124,000 pediatric hospitalizations annually. Those patients often have received antibiotics prior to admission. Many have concurrent viral infections. Bacterial infections accompanying viral respiratory infections are known to increase morbidity and mortality. Traditional bacterial culture methods are often negative because of previous antibiotic therapy. The BCID, a multiplex polymerase chain reaction(PCR) assay, can identify 19 bacterial pathogens in approximately 90 minutes. It is FDA approved for blood culture isolates. We hypothesized it would detect bacterial pathogens in pleural effusions. Methods BCID panels were done on residual pleural fluid samples from 10 patients with severe community acquired pneumonia during the period 5/2018 – 12/2019. The patients had positive radiographic findings of pneumonia, were inpatients, had intact immune systems by clinical history and had received antibiotic therapy for more than 8 hours before specimen collection. Treatment required 133 inpatient days. 6 of 10 were diagnosed with viral respiratory pathogens. 1 of 9 had a positive blood culture. 1 of 10 had a positive pleural fluid culture. Results 10 of 10 pleural fluid specimens were positive for a pathogen on the BCID panel – 8, Streptococcus pneumoniae, 1, Staphylococcus aureus and I, Streptococcus pyogens. Two of ten had confirmatory positive cultures. Also, one pleural fluid gram stain showed gram positive cocci in chains and clusters. The BCID detected Streptococcus pyogens. Anti Streptolysin O was strongly positive, 964(0 – 70) IU/mL. Conclusion The yield of bacterial culture plummets with previous antibiotic treatment. FDA approved multiplex PCR panels have narrowly defined specimen requirements. That increases the cost and decreases test applicability. Despite a history of appropriate immunizations in the sample population Streptococcus pneumoniae may be prevalent in the complex pediatric pneumonia population. The BCID may be effective at pathogen detection in cases of complex pneumonia where patients have received prior antibiotic treatment.

The STAPH Score: A Predictor of Staphylococcus aureus as the Causative Microorganism of Native Vertebral Osteomyelitis.

Background Staphylococcus aureus (SA) is the most common causative microorganism in native vertebral osteomyelitis (NVO). Few studies have compared the clinical features of NVO due to SA (SA-NVO) and NVO due to other organisms (NSA-NVO). This study was conducted to validate a predictive score for SA-NVO to facilitate NVO treatment without broad-spectrum antimicrobial agents.MethodsThis retrospective study compared the clinical features of patients with SA-NVO and NSA-NVO who were diagnosed from 2004 to 2019. Univariate associations were assessed using χ 2, Fisher’s exact, or Mann-Whitney U test. Multivariable analysis was conducted using logistic regression. The optimal age cutoff point was determined by classification and regression tree analysis.ResultsAmong 155 NVO patients, 98 (63.2%) had a microbiologically confirmed diagnosis: 40 (25.8%) with SA-NVO and 58 (37.4%) with NSA-NVO. Six predictors, either independently associated with SA-NVO or clinically relevant, were used to develop the STAPH prediction score: atopic dermatitis (Skin) (3 points); recent Trauma (2 points); Age < 67 years (1 point); Abscess (1 point); central venous Port catheter (2 points); and History of puncture (2 points). In a receiver operating characteristic analysis, the area under the curve was 0.84 (95% confidence interval, 0.76–0.91). The best cutoff point was 3. A score ≥3 had a sensitivity, specificity, positive predictive value, and negative predictive value of 58%, 84%, 84%, and 73%, respectively.ConclusionsThe STAPH score has relatively high specificity for use by clinicians to predict SA as the causative microorganism in patients with NVO until results of a confirmatory culture are available.

Predictive modeling of bacterial infections and antibiotic therapy needs in critically ill adults.

Unnecessary antibiotic regimens in the intensive care unit (ICU) are associated with adverse patient outcomes and antimicrobial resistance. Bacterial infections (BI) are both common and deadly in ICUs, and as a result, patients with a suspected BI are routinely started on broad-spectrum antibiotics prior to having confirmatory microbiologic culture results or when an occult BI is suspected, a practice known as empiric antibiotic therapy (EAT). However, EAT guidelines lack consensus and existing methods to quantify patient-level BI risk rely largely on clinical judgement and inaccurate biomarkers or expensive diagnostic tests. As a consequence, patients with low risk of BI often are continued on EAT, exposing them to unnecessary side effects. Augmenting current intuition-based practices with data-driven predictions of BI risk could help inform clinical decisions to shorten the duration of unnecessary EAT and improve patient outcomes. We propose a novel framework to identify ICU patients with low risk of BI as candidates for earlier EAT discontinuation. For this study, patients suspected of having a community-acquired BI were identified in the Medical Information Mart for Intensive Care III (MIMIC-III) dataset and categorized based on microbiologic culture results and EAT duration. Using structured longitudinal data collected up to 24-, 48-, and 72-hours after starting EAT, our best models identified patients at low risk of BI with AUROCs up to 0.8 and negative predictive values >93%. Overall, these results demonstrate the feasibility of forecasting BI risk in a critical care setting using patient features found in the electronic health record and call for more extensive research in this promising, yet relatively understudied, area.

Sputum culture and drug sensitivity testing outcome among X-pert Mycobacterium tuberculosis/rifampicin-positive, rifampicin-resistant sputum: A retrospective study — Not all rifampicin resistance is multi-drug resistant

ObjectiveRifampicin-resistant (RR) tuberculosis (TB) on X-pert Mycobacterium tuberculosis/rifampicin (MTB/Rif) is assumed to be a surrogate for multi-drug resistant (MDR) TB. Following an RR result, a second specimen was taken for confirmatory culture and drug-susceptibility testing (DST). This study compared the initial diagnostic X-pert MTB/RIF result with the confirmatory DST in a high human immunodeficiency virus (HIV) seroprevalence setting. DesignRecords analysing demographics, HIV serostatus, prior TB treatments, and DST results were retrospectively reviewed. ResultsOf 604 patients with X-pert MTB/RIF RR, 374 (61.9%) had DST and were included. The mean age was 36.9 years and 82% were HIV infected. Following DST, MDR was confirmed in 49% and Rif mono-resistant (RMR) TB in 36%. Amongst RMR TB, 84% were HIV-infected, and amongst those with CD4 < 50 versus those 50–350 cells/mm3 RMR TB was noted in 51% versus 33%, respectively (P = 0.012). Primary DR was diagnosed in 43% (61% MDR and 33% RMR). ConclusionRifampicin resistance detected on a diagnostic X-pert MTB/Rif assay did not always predict MDR. Rifampicin mono-resistance is emerging amongst those with HIV co-infection and low CD4 counts (<50 cells/mm3). Research is needed to reduce the number of drugs and treatment durations for RMR TB.

How Testing Drives Treatment in Asymptomatic Patients: Level of Pyuria Directly Predicts Probability of Antimicrobial Prescribing.

Urinalysis is a readily available test often used for screening. Pyuria is a common finding in asymptomatic patients; however, it is unknown how often identification of pyuria in the absence of confirmatory cultures leads to antimicrobial prescribing. The objective of this study was to measure the association between pyuria and antimicrobial initiation during the perioperative period and assess harms versus benefits of treatment. A retrospective cohort of preoperative patients within the national healthcare system during the period 1 October 2008-30 September 2013 who had a urinalysis performed during the 30-day preoperative period was created; patients with positive urine cultures were excluded. The primary exposure was pyuria on preoperative urinalysis. The primary outcome was antimicrobial initiation. Secondary outcomes included postoperative surgical site (SSI), urinary tract (UTI), and Clostridioides difficile infections. Trend and logistic regression analyses were performed. Among 41 373 patients, 3617 had pyuria. 887 (24.5%) patients with pyuria received antimicrobials versus 1918 (5.1%) patients without pyuria. As the degree of pyuria increased, the odds of receiving antimicrobials also increased linearly (low, 14.7%; moderate, 24.0%; high pyuria, 37.4%). Preoperative pyuria was associated with postoperative C. difficile infections (aOR, 1.7; 95% CI, 1.2-2.4); risk was higher in patients who received antimicrobials (aOR, 2.4; 1.7-3.4). Pyuria was not associated with SSI but was associated with increases in UTI after orthopedic and vascular procedures; this risk was not mitigated by antimicrobial therapy. Urine screening during the preoperative period is a low-value intervention that increases antimicrobial exposure but does not improve postoperative outcomes.

Incidence of tuberculosis among HIV infected individuals on long term antiretroviral therapy in private healthcare sector in Pune, Western India

BackgroundDespite rapid scale up of antiretroviral therapy (ART), Tuberculosis (TB) remains the commonest opportunistic infection and cause of death among HIV infected individuals in resource limited settings like India. Incidence of TB in individuals on ART in private healthcare sector in India is infrequently studied.MethodsThis retrospective cohort study conducted between 1st March 2009 and 1st March 2017 aimed to evaluate rate of incident TB in individuals initiated on ART at 3 private sector ART clinics in Pune, India. Individuals more than 12 years of age with ART duration of atleast 6 months were included. Patients were classified as having prevalent TB if they had a TB episode within the year prior to ART initiation or if they developed TB within 6 months of starting ART. Individuals who were diagnosed with TB after 6 months of starting ART were classified as incident TB cases. A recurrent episode of TB after treatment completion or cure of prevalent TB was also regarded as incident TB. Patients were classified as definitive TB if Mycobacterium tuberculosis was grown in culture from a biological sample or a positive rapid molecular test. Patients were classified as probable TB if there was radiologic evidence of TB in absence of confirmatory culture or PCR.Results1904 patients with a median duration of follow up on ART of 57 (IQR = 32.0, 84.0) months were included. Of these, 182 developed incident TB (22% definitive TB, 38% recurrent cases). TB incidence at 6–12 months, 13–24 months, 25–60 months and > 60 months of ART was 24.32, 5.46, 2.54 and 0.75 cases per 100 person years respectively. Current time updated CD4 count < 500 cells/mm3 (p < 0.0001), virologic failure on ART (adjusted Hazard Ratio (aHR): 3.05 (95% CI: 2.094, 4.454), p < 0.0001) and receipt of ART without IPT (aHR: 8.24 (95% CI, 3.358, 20.204), p < 0.0001) were associated with higher risk of incident TB.ConclusionStarting ART early in treatment naïve individuals, prompt detection of virologic failure on ART and providing IPT along with ART will be useful in reducing incident TB. Efforts from private sector are crucial in achieving Sustainable Development Goals set by Government of India and attaining the vision of a TB free India.

Direct detection of bacteremia by exploiting host-pathogen interactions of lipoteichoic acid and lipopolysaccharide

Bacteremia is a leading cause of death in sub-Saharan Africa where childhood mortality rates are the highest in the world. The early diagnosis of bacteremia and initiation of treatment saves lives, especially in high-disease burden areas. However, diagnosing bacteremia is challenging for clinicians, especially in children presenting with co-infections such as malaria and HIV. There is an urgent need for a rapid method for detecting bacteremia in pediatric patients with co-morbidities to inform treatment. In this manuscript, we have developed and clinically validated a novel method for the direct detection of amphiphilic pathogen biomarkers indicative of bacteremia, directly in aqueous blood, by mimicking innate immune recognition. Specifically, we have exploited the interaction of amphiphilic pathogen biomarkers such as lipopolysaccharides (LPS) from Gram-negative bacteria and lipoteichoic acids (LTA) from Gram-positive bacteria with host lipoprotein carriers in blood, in order to develop two tailored assays – lipoprotein capture and membrane insertion – for their direct detection. Our assays demonstrate a sensitivity of detection of 4 ng/mL for LPS and 2 ng/mL for LTA using a waveguide-based optical biosensor platform that was developed at LANL. In this manuscript, we also demonstrate the application of these methods for the detection of LPS in serum from pediatric patients with invasive Salmonella Typhimurium bacteremia (n = 7) and those with Staphylococcal bacteremia (n = 7) with 100% correlation with confirmatory culture. Taken together, these results demonstrate the significance of biochemistry in both our understanding of host-pathogen biology, and development of assay methodology, as well as demonstrate a potential new approach for the rapid, sensitive and accurate diagnosis of bacteremia at the point of need.

Diagnosis and antibiotic treatment of group a streptococcal pharyngitis in children in a primary care setting: impact of point-of-care polymerase chain reaction

BackgroundTo compare the sensitivity and specificity of the recommended 2-step rapid antigen detection test (RADT) with confirmatory culture vs the point-of-care (POC) polymerase chain reaction (PCR) Roche cobas® Liat® Strep A test for detection of group A Streptococcus (GAS) in pediatric patients with pharyngitis, and to investigate the impact of these tests on antibiotic use in a large pediatric clinic.MethodsThis prospective, open-label study was conducted at a single site during fall/winter 2016–2017. A total of 275 patients aged 3 to 18 years with symptoms of pharyngitis had a throat-swab specimen analyzed using RADT, POC PCR, and culture. The sensitivity, specificity, and percentage agreement (95% CI) between assays and a laboratory-based nucleic acid amplification test were calculated. DNA sequencing was used to adjudicate discrepancies. The RADT or POC PCR result was provided to clinicians on alternating weeks to compare the impact on antibiotic use.ResultsA total of 255 samples were evaluated; 110 (43.1%) were GAS positive. Sensitivities (95% CI) for POC PCR, RADT, and culture were 95.5% (89.7–98.5%), 85.5% (77.5–1.5%), and 71.8% (62.4–80.0%), respectively. Specificities (95% CI) for POC PCR, RADT, and culture were 99.3% (96.2–99.98%), 93.7% (88.5–97.1%), and 100% (97.5–100%), respectively. Compared with RADT, POC PCR resulted in significantly greater appropriate antibiotic use (97.1% vs 87.5%; P = .0065).ConclusionUnder real-world conditions, RADT results were less specific and culture results were less sensitive than found in established literature and led to increased rates of inappropriate antibiotic use. POC PCR had high sensitivity and specificity and rapid turnaround times, and led to more appropriate antibiotic use.Trial registrationID number ISRCTN84562679. Registered October 162,018, retrospectively registered.

How to Identify Exposed Women Who Are Infected with Neisseria gonorrhoeae.

Treatment trials of antibiotics for Neisseria gonorrhoeae infections frequently enroll primarily men with urethritis, as the diagnosis of acute gonococcal infection in men with urethritis is easily made by Gram stain of the urethral exudate, followed by confirmatory culture or nucleic acid amplification tests (NAATs). Enrolling women in treatment trials is of great importance, but N. gonorrhoeae cervical infections cause nonspecific symptoms. This makes it difficult to conduct interventional trials, as large numbers of women with nonspecific symptoms need to be screened for infection. Gram stain of cervical secretions has a strikingly low sensitivity, and culture and/or NAAT results are not available at the time of screening. This necessitates recall and delayed treatment of infected women who may not return and who may spread the infection during the interval. In this chapter we present an algorithm, derived from a comparison of women who did, or did not, become infected during exposure, which identifies those women who are highly likely to be infected before culture and/or NAAT results are available. The algorithm provides an efficient way to conduct interventional trials in women without the problem of recall and delayed treatment.

Laboratory Capacity for Surveillance of Infectious Diseases in Gujarat: Quantity, Quality, Effects and Way Forward

Background: India carries one of the largest burdens of infectious diseases in the world. To estimate this, laboratory confirmation is vital. We estimated the lab capacity and effectiveness in the state of Gujarat for Enteric Fever, Infectious Hepatitis, and Dengue. Methods: We estimated the number of labs in the state through telephonic surveys and physical screening of a representative sample of labs. We created four levels of tests, Level-0 being no test and 3 being the best confirmatory test available in the state. For the profusion of rapid diagnostic test kits (RDTKs), we constructed Effective Diagnostic Scores (EDS) calculated from their sensitivity and specificity at disease prevalences specified in the literature. Tests with EDS > 0.51 were level-2 tests, and EDS < 0.50, level-1 tests. Results: Our analysis showed that there are 4293 labs in the state (1765 public and 2528 private), 7/100,000 population. However, only 2878 labs contributed to a total pooled Effective Lab Diagnostic Score (ELDS) of 6776 in the state. Strikingly, 94% of the lab effectiveness lay in RDTs (level-2 and 1 tests) which are essentially screening tests. Ninety-six percent of the overall lab effectiveness of Gujarat existed in private and only 4% in public labs. Contrarily, the level-3 confirmatory testing effectiveness, through ELISA and culture constituted only 4% of private and 36% of public lab effectiveness. More than half of the private lab effectiveness was located in eight Tier 1 cities. Level-3 confirmatory testing effectiveness was present only in Tier 1 and 2 towns. Hepatitis B testing contributed 34% of the total ELDS, followed by Dengue (30%), Enteric Fever (26%) and Hepatitis A and E (10%). Conclusion: Our study has established that the capacity and effectiveness of the lab network in Gujarat lie predominantly in RDTKs. We need to adapt our systems to capture this data in a manner that will allow us to monitor the burdens of these diseases.

High Prevalence of Sterile Pyuria in the Setting of Sexually Transmitted Infection in Women Presenting to an Emergency Department.

IntroductionThe clinical presentations for sexually transmitted infections (STI) and urinary tract infections (UTI) often overlap, and symptoms of dysuria and urinary frequency/urgency occur with both STIs and UTIs. Abnormal urinalysis (UA) findings and pyuria are common in both UTIs and STIs, and confirmatory urine cultures are not available to emergency clinicians to aid in decision-making regarding prescribing antibiotics for UTIs. The objective of this study was to determine the frequency of sterile pyuria in women with confirmed STIs, as well as whether the absolute number of leukocytes on microscopy or nitrite on urine dipstick correlated with positive urine cultures in patients with confirmed STIs. We also sought to determine how many patients with STIs were inappropriately prescribed a UTI antibiotic.MethodsWe performed a retrospective chart review of patients aged 18–50 who had a urinalysis and pelvic examination in the emergency department (including cervical cultures), and tested positive for Neisseria gonorrhoeae, Chlamydia trachomatis, and/or Trichomonas vaginalis. Descriptive statistics were obtained for all variables, and associations between various findings were sought using the Fisher’s exact test for categorical variables. We calculated comparison of proportions using the N-1 chi-squared analysis.ResultsA total of 1,052 female patients tested positive for Neisseria gonorrhoeae, Chlamydia trachomatis, and/or Trichomonas vaginalis and were entered into the database. The prevalence of pyuria in all cases was 394/1,052, 37% (95% confidence interval [CI] [0.34–0.40]). Of the cases with pyuria, 293/394, 74% (95% CI [0.70–0.78]) had sterile pyuria with negative urine cultures. The prevalence of positive urine cultures in our study population was 101/1,052, 9.6% (95% CI [0.08–0.11]). Culture positive urines had a mean of 34 leukocytes per high-power field, and culture negative urines had a mean of 24 leukocytes per high-power field, with a difference of 10, (95% CI [3.46–16.15]), which was statistically significant (p=0.003). Only 123 cases tested positive for nitrite on the urinalysis dipstick; 50/123, 41% (95% CI [0.32–0.49]) had positive urine cultures, and 73/123, 59% (95% CI [0.51–0.68]) had negative urine cultures. Nitrite-positive urines were actually 18% more likely to be associated with negative urine cultures in the setting of positive STI cases, (95% CI [4.95–30.42], p=0.0048). Antibiotics were prescribed for 295 patients with suspected UTI. Of these, 195/295, 66% (95% CI [0.61–0.71]) had negative urine cultures, and 100/295, 34% (0.33, 95% CI [0.28–0.39]) had positive urine cultures. Chi-square analysis yielded a difference of these proportions of 32% (95% CI [23.92–39.62], p<0.0001).ConclusionThis study demonstrated that in female patients with STIs who have pyuria, there is a high prevalence of sterile pyuria. Our results suggest that reliance on pyuria or positive nitrite for the decision to add antimicrobial therapy empirically for a presumed urinary tract infection in cases in which an STI is confirmed or highly suspected is likely to result in substantial over-treatment.

Clinical course in infants diagnosed with transient tachypnea of newborn: A clinical trial assessing the role of conservative versus conventional management

BackgroundTransient tachypnea of the newborn (TTN) is a respiratory disorder secondary to inadequate or delayed clearance of lung fluids. Early symptoms of the disease are indistinguishable from neonatal respiratory distress syndrome, pneumonia, and persistent pulmonary hypertension. Therefore, these newborns, in addition to receiving conservative management, receive antibiotics until blood cultures provide definite results. In this study, we assessed the clinical course of neonates diagnosed with TTN who received conventional versus conservative management. MethodsOne hundred and thirty neonates diagnosed as having TTN were randomly enrolled in two study groups. While patients belonging to one group received conservative management, those from the other group were treated with conventional medical therapy. ResultsMean duration of hospitalization was 7 ± 0.2 in the conventional and 5 ± 1.5 in the conservative group. Duration of antibiotic therapy was 6.7 ± 2.47 days in the conventional group. ConclusionNewborns diagnosed with TTN without prenatal risk factors and a negative C reactive protein test do not need to be administered antibiotics and hospitalized until confirmatory blood culture results are obtained.

Residual risk of bacterial contamination of platelets: six years of experience with sterility testing.

Canadian Blood Services screens 100% of platelet concentrates (PCs) for bacterial contamination with the BacT/ALERT system. Quality-control sterility testing of 1% (≥10 units) of outdated PCs is performed monthly. Data from routine screening, quality-control testing, and septic reactions obtained from 2010 to 2016 are presented herein. In total, 601,988 buffy coat PC pools and 186,737 apheresis PCs were routinely screened with aerobic cultures over 6 years. Outdate quality-control testing of 8535 buffy coat and 8498 apheresis PCs was performed using aerobic and anaerobic cultures during the same period. Results were classified as "true-positives" when the same bacterium was isolated in initial and confirmatory cultures or "false-negatives" when bacteria were missed in early screening and were captured during quality-control sterility testing or through investigation of sepsis cases. During routine screening, the true-positive rates between buffy coat (0.94 per 10,000) and apheresis (0.96 per 10,000) PCs were similar (p = 0.9473). Seventy-five bacteria isolated during PC screening included Gram-positive and Gram-negative organisms. Six false-negative septic reactions were reported that implicated coagulase-negative staphylococci (n = 3) and Staphylococcus aureus (n = 3) for approximate rates of 1 per 100,000 transfusion reactions and 1 per 500,000 fatalities. During quality-control testing, the false-negative rates between buffy coat (8 per 10,000) and apheresis (9 per 10,000) PCs were similar (p = 0.7897). All 15 quality-control isolates were Gram-positive bacteria. The current bacterial screening protocol is efficacious for identifying Gram-negative bacteria. However, the high proportion of Gram-positive organisms detected on outdate quality-control testing and septic transfusion events demonstrates a residual safety risk that merits further intervention.

The 2015 New York City Legionnaires' Disease Outbreak: A Case Study on a History-Making Outbreak.

The 2015 New York City Legionnaires' Disease Outbreak: A Case Study on a History-Making Outbreak.