Background: Bloodstream infection is a common cause of hospitalization, morbidity and death in children. The impact of antimicrobial resistance and HIV infection on outcome is not firmly established.

Extended-spectrum beta-lactamases (ESBLs) were present in high proportions of Escherichia coli (25% [9 of 36]) and Klebsiella pneumoniae isolates (17% [9 of 52]) causing pediatric septicemia at a tertiary hospital in Tanzania. Patients with septicemia due to ESBL-producing organisms had a significantly higher fatality rate than those with non-ESBL isolates (71% versus 39%, P ‫؍‬ 0.039). This is the first report of the CTX-M-15 genotype of ESBLs on the African continent and the first observation of SHV-12 genotype in an isolate of Salmonella enterica serotype Newport. Resistance to beta-lactam antibiotics was demonstrated inEscherichia coli even before penicillin was released for clinical use. In the 1960s, the first plasmid-transferable beta-lactamase was discovered and named TEM-1 after Temoniera, the Greek girl who harbored the E. coli isolate from which the enzyme was obtained. Since the 1980s, a large number of plasmid-transferable extended-spectrum beta-lactamases (ESBLs) capable of inactivating extended-spectrum cephalosporins has been discovered (6). Most of the ESBLs are derived from TEM-1 and SHV-1 (sulfhydryl variable) by mutations. ESBLs have spread widely and have become a major cause of nosocomial infections associated with high mortality rates, particularly in serious infections such as septicemia (12). In Africa, ESBLs have been reported in Egypt (19), Tunisia (4, 5), Morocco (2), Senegal (18,20), Nigeria (1), South Africa (9), and Kenya (11) but not previously from Tanzania. In the present study, we investigated the prevalence and clinical implications of ESBL production in E. coli, Klebsiella pneumoniae, and salmonellae causing septicemia in infants and children admitted to a tertiary teaching hospital in Tanzania. MATERIALS AND METHODSFrom August 2001 to August 2002, blood cultures were obtained from 1,798 children aged 0 to 7 years with a fever of Ն38°C or other signs of severe infections admitted to the Pediatric Department at Muhimbili National Hospital, a tertiary referral hospital in Dar es Salaam, Tanzania. We included in the present study 113 children who had growth in blood culture of one or more isolates of E. coli, Klebsiella spp., or salmonellae.Blood specimens (1 ml from neonates and 5 ml from older children) were inoculated in BACTEC Myco/F lytic blood culturing vials (Becton Dickinson, Franklin Lakes, N.J). Positive blood cultures were subcultured on Columbia II agar base (Oxoid Ltd, Basingstoke, United Kingdom) with 5% human blood, chocolate agar, and MacConkey agar (Difco/BD Diagnostic Systems, Sparks, Mich.). The isolates were identified according to established procedures (7).Klebsiella spp. were identified with the API 20E system (bioMérieux SA, Marcy l'Etoile, France). Susceptibilities against antimicrobial agents were tested by the disk diffusion method according to NCCLS guidelines (15). Isolates of E. coli, Klebsiella spp., and salmonellae with reduced susceptibilities to cefotaxime (zone diameter of Յ27 mm) and/or ceftazidime (zone diameter of Յ22 mm) according to guidel...

Background Key knowledge gaps remain in the understanding of viral dynamics and immune response of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Methods We evaluated these characteristics and established their association with clinical severity in a prospective observational cohort study of 100 patients with PCR-confirmed SARS-CoV-2 infection (mean age, 46 years; 56% male; 38% with comorbidities). Respiratory samples (n = 74) were collected for viral culture, serum samples for measurement of IgM/IgG levels (n = 30), and plasma samples for levels of inflammatory cytokines and chemokines (n = 81). Disease severity was correlated with results from viral culture, serologic testing, and immune markers. Results Fifty-seven (57%) patients developed viral pneumonia, of whom 20 (20%) required supplemental oxygen, including 12 (12%) with invasive mechanical ventilation. Viral culture from respiratory samples was positive for 19 of 74 patients (26%). No virus was isolated when the PCR cycle threshold (Ct) value was >30 or >14 days after symptom onset. Seroconversion occurred at a median (IQR) of 12.5 (9–18) days for IgM and 15.0 (12–20) days for IgG; 54/62 patients (87.1%) sampled at day 14 or later seroconverted. Severe infections were associated with earlier seroconversion and higher peak IgM and IgG levels. Levels of IP-10, HGF, IL-6, MCP-1, MIP-1α, IL-12p70, IL-18, VEGF-A, PDGF-BB, and IL-1RA significantly correlated with disease severity. Conclusions We found virus viability was associated with lower PCR Ct value in early illness. A stronger antibody response was associated with disease severity. The overactive proinflammatory immune signatures offer targets for host-directed immunotherapy, which should be evaluated in randomized controlled trials.

IgG assay in COVID-19 patients. Methods: Residual sera from 177 symptomatic SARS-CoV-2-positive patients and 163 non-COVID-19 patients were tested for antibody with the Abbott SARS-CoV-2 IgG assay (Abbott Diagnostics, Chicago, USA). Clinical records for COVID-19 patients were reviewed to determine the time from onset of clinical illness to testing. Results: Specificity of the assay was 100.0% (95%CI: 97.1e100.0%). The clinical sensitivity of the assay varied depending on time from onset of symptoms, increasing with longer periods from the onset of clinical illness. The clinical sensitivity at 6 days was 8.6% (7/81; 95%CI: 3.8e17.5%), at 7e13 days 43.6% (17/39; 95%CI: 28.2e60.2%), at 14e20 days 84.0% (21/25; 95%CI: 63.1e94.7%), and at 21 days 84.4% (27/ 32; 95%CI: 66.5e94.1%). Clinical sensitivity was higher in the 14-day group compared to <14 days. There were no differences between the 14e20-day and 21-days groups; the combined clinical sensitivity for these groups (14 days) was 84.2% (49/57; 71.6e92.1%). Conclusion:The Abbott SARS-CoV-2 IgG test has high specificity. Clinical sensitivity was limited in the early stages of disease but improved from 14 days after the onset of clinical symptoms.

Particle sorting methods in microfluidic platforms are gaining momentum for various biomedical applications. Bioparticles are found in different shapes and sizes. However, conventional separation techniques are mainly designed for separation of spherical particles. Thus, there is a need to develop new methods for effective separation of spherical and non-spherical bioparticles for various applications. Deterministic lateral displacement (DLD) microfluidic methods have become popular for high separation resolution, simplicity, and predictability. However, shape sorting in the DLD separation methods is not well researched. Recently, we explored this area and found that pillar shapes in DLD significantly affect bioparticle separation. In this work, we designed a group of different pillar shapes with protrusions and groove structures with the hypothesis that pillar protrusions will induce particle rotation while pillar grooves will confine the particle rotational movement in a directed path for effective separation in a DLD pillar array. Using combinations of protrusions and grooves, 3-dimensional spherical particles, 2-dimensional planar disc-shaped red blood cells and 1-dimensional rod-shaped bacteria were separated and two interesting phenomena were observed. Firstly, the arrangement of pillar protrusions and grooves induces inertial movements, enhancing the separation of spherical particles. Secondly, non-spherical particles experience dominant rotational movements due to the protrusions and grooves which help in changing their orientations. This gives an opportunity to perform efficient separation based on the desired orientation (the longest dimension of the particles) by restricting or containing their movement within a specific DLD path.

Background: Resistance to third generation cephalosporins due to acquisition and expression of extended spectrum β-lactamase (ESBL) enzymes among Gram-negative bacteria is on the increase. Presence of ESBL producing organisms has been reported to significantly affect the course and outcome of an infection. Therefore infections due to ESBL isolates continue to pose a challenge to infection management worldwide. The aim of this study was to determine the existence and to describe phenotypic and genotypic characteristics of ESBLs in an Intensive Care Unit (ICU) setting in Tanzania.

A new national antimicrobial resistance surveillance program in Singapore public hospitals that uses WHONET detected high levels of methicillin resistance among Staphylococcus aureus (35.3%), carbapenem resistance among Acinetobacter spp. (49.6%), and third-generation cephalosporin resistance among Klebsiella pneumoniae (35.9%) hospital isolates in 2006. Antimicrobial drug resistance is a major problem in Singapore.

We evaluated the impact of a prospective audit and feedback antimicrobial stewardship program (ASP) on antibiotic prescription and resistance trends in a hematology-oncology unit in a university hospital (National University Cancer Institute, Singapore [NCIS]). A prospective interrupted time-series study comprising 11-month pre-intervention (PIP) and intervention evaluation phases (IEP) flanking a one-month implementation phase was carried out. Outcome measures included defined daily dose per 100 (DDD/100) inpatient-days of ASP-audited and all antibiotics (encompassing audited and non-audited antibiotics), and the incidence-density of antibiotic-resistant microorganisms at the NCIS. Internal and external controls were DDD/100 inpatient-days of paracetamol at the NCIS and DDD/100 inpatient-days of antibiotics prescribed in the rest of the hospital. There were 580 ASP recommendations from 1,276 audits, with a mean monthly compliance of 86.9%. Significant reversal of prescription trends towards reduced prescription of audited (coefficient = -2.621; 95% confidence interval [CI]: -4.923, -0.319; p = 0.026) and all evaluated antibiotics (coefficient = -4.069; 95% CI: -8.075, -0.063; p = 0.046) was observed. No changes were seen for both internal and external controls, except for the reversal of prescription trends for cephalosporins hospital-wide. Antimicrobial resistance did not change over the time period of the study. Adverse outcomes-the majority unavoidable-occurred following 5.5% of accepted ASP recommendations. Safe and effective ASPs can be implemented in the complex setting of hematology-oncology inpatients.