Molecular surveillance reveals widespread colonisation by carbapenemase and extended spectrum beta-lactamase producing organisms in neonatal units in Kenya and Nigeria

Objectives Neonatal sepsis, a major cause of death amongst infants in sub-Saharan Africa, is often gut derived. Impairments in immunity and the gut barrier in sick neonates allow colonisation by opportunistic pathogens such as Enterobacteriaceae to progress to blood stream infection. Colonisation by Enterobacteriaceae producing extended spectrum beta-lactamase (ESBL) or carbapenemase enzymes is particularly problematic and can lead to antimicrobial-resistant (AMR) or untreatable infections. We sought to explore the rates of colonisation by ESBL or carbapenemase producers and their genotypes in two neonatal units (NNUs) in West and East Africa. Methods Stool and rectal swab samples were taken at multiple timepoints from newborns admitted to the NNUs at the University College Hospital, Ibadan, Nigeria and the Jaramogi Oginga Odinga Teaching and Referral Hospital, Kisumu, western Kenya. Samples were tested for ESBL and carbapenemase genes using a previously validated qPCR assay with high resolution melt analysis. Kaplan-Meier survival analysis was used to examine colonisation rates at both sites. Results A total of 119 stool and rectal swab samples were taken from 42 infants admitted to the two NNUs. Six (14.3%) infants were extremely preterm (gestation <28 weeks), 19 (45.2%) were born by Caesarean section and 3 (8.6%) mothers were HIV positive. Median (IQR) duration of admission was 12.5 (5-26) days and 12 (28.6%) infants died. Overall, colonisation with ESBL (37 infants, 89%) was more common than with carbapenemase producers (26, 62.4%; P = 0.093). Median survival time before colonisation with ESBL organisms was 7 days and with carbapenemase producers 16 days (P=0.035). The majority of ESBL genes detected belonged to the CTX-M-1 (36/38; 95%), and CTX-M-9 (2/36; 5%) groups. The most prevalent carbapenemase was blaNDM (27/29, 93%). Single blaVIM (1/32, 3%) and blaOXA-48 genes (1/32, 3%) were also detected. Conclusions Gut colonisation of neonates by AMR organisms was common and occurred rapidly in NNUs in Kenya and Nigeria. Active surveillance of colonisation will improve the understanding of AMR in these settings and guide infection control and antibiotic prescribing practice to improve clinical outcomes.

Evaluation of an ultra-rapid antibiotic susceptibility testing method on positive blood cultures with Escherichia coli

Blood stream infection (BSI) is related to high mortality and morbidity. Early antimicrobial therapy is crucial in treating patients with BSI. The most common Gram-negative bacteria causing BSI is Escherichia coli. Targeted effective treatment of patients with BSI is only possible if it is based on antibiotic susceptibility testing (AST) data after blood culture positivity. However, there are very few methods available for rapid phenotypic AST and the fastest method takes 4 h. Here we analyzed the performance of a 30 min ultra-rapid method for AST of E. coli directly from positive blood cultures (BC). In total, 51 positive BC with E. coli were studied, and we evaluated the ultra-rapid method directly on positive BC as well as on E. coli colonies cultured on agar plates. The results obtained by the new method were compared with disk diffusion. The method provided accurate AST result in 30 min to Ciprofloxacin and Gentamicin for 92% and 84% of the positive BC samples, respectively. For E. coli isolates retrieved from agar plates, 86% and 96% of the AST results were accurate for Ciprofloxacin and Gentamicin, respectively, after 30 min of assay time. When time to result was modulated in-silico from 30 to 60 minutes for the agar plate samples, accuracy of AST results went up to 92% for Ciprofloxacin and to 100% for Gentamicin. The present study shows that the method is reliable and delivers ultra-rapid AST data in 30 minutes directly from positive BC and as well as from agar plates.

Polymyxin B infusion related respiratory arrest: A case report

A 73 years old male, known hypertensive on medication, with the history of SARS-CoV-2 infection nine months ago, presented to us with mucormycosis, he was treated with Liposomal amphotericin B initially. He developed acute kidney injury with recurrent pulmonary oedema requiring ICU admission and Haemodialysis. He later developed catheter related blood stream infection that grew Carbapenem resistant Klebsiella pneumonia and was started on Polymyxin B. However from day 3 of antibiotics he started to develop recurrent respiratory arrest with no apparent cause. He required a brief period of mechanical ventilation and was successfully weaned. He had recurrent such episodes with no apparent cause. After extensive work up and literature search it was diagnosed as Polymyxin B induced respiratory failure. Polymyxins were stopped, patient was discharged in a stable condition after five days of further observation and is currently on follow up with no such episode of dyspnoea.

Bacterial and fungal profile, drug resistance pattern and associated factors of isolates recovered from blood samples of patients referred to Ethiopian Public Health Institute: cross-sectional study

Background Blood stream infections are serious infections that usually induce prolongation of hospital stay, morbidity and mortality in several countries including Ethiopia. The aim of this study was to determine bacterial and fungal profile, their drug resistance patterns, and risk factors associated with blood stream infections. Methods A cross sectional study design was conducted from February 23 to June 23, 2020 at Ethiopian public health. A structured questionnaire was used to collect data on socio-demographic factors and clinical conditions. Blood specimens were analyzed using standard microbiological techniques. Antimicrobial susceptibility tests were performed using Kirby–Bauer disc diffusion technique and Vitek compact 2. Simple and multiple logistic regressions were used to assess the potential risk factors. Results A total of 175 pathogens isolated from 346 blood specimens. Of these, 60% Gram-negative bacteria, 30.86% Gram-positive bacteria and 9.14% fungal isolates were identified. Burkholderia cepacia and Coagulase negative staphylococcus were the predominant pathogen among Gram-negative and Gram-positive bacteria respectively. Among fungus, Candida krusei (56.25%) was the most predominant isolate. The highest proportions of antibacterial resistance were observed among 3rd generation cephalosporin and penicillin. Most fungal isolates expressed resistance to fluconazole. Sex (P = 0.007), age (P < 0.001) and use of invasive medical devices (P = 0.003) were identified as risk factors for bacterial blood stream infections. Conclusion The study showed high prevalence of blood stream infection was due to B. cepacia and non-C. albicans spp. This finding alarming ongoing investigation of blood stream infection is important for recognizing future potential preventive strategies including environmental hygiene and management of comorbid medical diseases to reduce the problem.

Prevention and Nursing Management for Central Line Associated Blood Stream Infection

Central line associated blood stream infection (CLABSI), is a substantial contributor to in-hospital morbidity and death, as well as increased cost and length of stay in the intensive care unit (ICU). CLABSIs are one of the most deadly for each infection is expected to have a mortality rate of 12-25 percent. CLABSI prevention is important, and nurses play a vital role. Nurses are required to complete initial training as well as annual competence tests for central venous catheter protocol and other skills to ensure that they are delivering direct care to patients using the most up-to-date evidence-based practices. Conclusion: CLABSI prevention bundles are the best method for implementing many interventions at once in addition to standardizing practice. Standard prevention bundles in addition to routine CLABSI education for staff are the most effective methods for preventing infection; it is inevitable that compliance with bundles will vary across healthcare institutions.

Pathogens and antimicrobial resistance amongst stroke patients in the intensive care unit: A five years review from Benin City, Nigeria

Severe stroke may necessitate intensive care unit admission, but there is a heightened risk of acquiring infection with use of ICU devices. Data regarding infection, pathogens and microbial resistance amongst stroke patients admitted into the ICU is scanty in Nigeria. This study aims to describe the infections, pathogens and antibiotics resistance pattern amongst stroke patients admitted into the ICU. It was a retrospective study. The ICU admission records of all stroke patients at the University of Benin Teaching Hospital from January 2014 to September 2019 were reviewed. The data obtained were the demographics, the types of stroke, results of microbiological studies on endotracheal aspirates, urine specimen, blood specimen, wound swab, vascular catheters, urinary catheters and the antibiogram pattern. One hundred and eight stroke patients were admitted into the ICU during the 5-year under review. The mean age was 61.8 with 51% being females and 52% having ischemic stroke. Seventy-five percent of the stroke patient had hospital acquired infection. Ventilator associated pneumonia accounted for 67.1% of infections, urinary tract infection was 22.8%, and blood stream infection 6.3% while 3.7% had infected decubitus ulcers. Microbial isolates were, Enterobacter sakazakii, accounting for 43.5%, Klebsiella pneumonia 13%, Escherichia coli 11.1%, and Proteus mirabilis 7.4% while 48% had Plasmodium falciparum infection. The micro-bacteria isolates were multi-antibiotics resistant, with the highest resistance for cotrimazole, cefuroxime and ceftazidime. The stroke patient in the ICU is susceptible to developing drug resistant hospital acquired infections, which could increase mortality. Ensuring minimal cases of ICU infection with continuous antimicrobial surveillance and robust antibiotics policy should be the goal.

Understanding Preventable Deaths in the Geriatric Trauma Population: Analysis of 3,452,339 Patients From the Center of Medicare and Medicaid Services Database

Background Patient safety indicators (PSIs) are avoidable complications that can impact outcomes. Geriatric patients have a higher mortality than younger patients with similar injuries, and understanding the etiology may help reduce mortality. We aim to estimate preventable geriatric trauma mortality in the United States and identify PSIs associated with increased preventable mortality. Methods A retrospective cohort study of patients aged ≥65 years, in the CMS database, 2017-second quarter of 2020. Risk-adjusted multivariable regression was performed to calculate observed-to-expected (O/E) mortality ratios for failure-to-prevent and failure-to-rescue PSIs with significance defined as P < .05. Results 3,452,339 geriatric patients were analyzed. Patients aged 75-84 years had 33% higher odds of preventable mortality (adjusted odds ratio [aOR] = 1.33 and 95% confidence interval [CI] = 1.31, 1.36), whereas patients aged ≥85 years had 91% higher odds of preventable mortality (aOR = 1.91 and 95% CI = 1.87, 1.94) compared to patients aged 65-74 years. Failure-to-prevent O/E were >1 for all PSIs evaluated with central line–related blood stream infection having a high O/E (747.93). Failure-to-rescue O/E were >1 for 10/11 (91%) PSIs with physiologic and metabolic derangements having the highest O/E (5.98). United States’ states with higher quantities of geriatric trauma patients experienced reduced preventable mortality. Conclusion Odds of preventable mortality increases with age. Perioperative venous thrombotic events, hemorrhage or hematoma, and postoperative physiologic/metabolic derangements produce significant preventable mortalities. United States’ states differ in their failure-to-prevent and failure-to-rescue PSIs. Utilization of national guidelines, minimization of central venous catheter use, addressing polypharmacy especially anticoagulation, ensuring operative and procedure-based competencies, and greater incorporation of inpatient geriatricians may serve to reduce preventable mortality in elderly trauma patients.

A Review on the Reported Antibacterial Activity of 1,3,5-Triazine

Antibiotics are the class of drugs used for bacterial, viral & fungal infection. Antibiotic resistance is the ability of microorganism to withstand themselves against the effects of a drug. Every year antibiotic resistance causes more than 38000 deaths in Thailand, 23000 deaths in USA. In South Asia one new born child dies every 5 minutes from blood stream infection because antibiotics given are ineffective due to bacterial resistance. Now antibiotic resistance is a threat to global health. In this paper, triazene derivatives are kept in concern. Triazines are six-membered, nitrogen-containing heterocyclic scaffold with a wide range of pharmaceutical properties such as antibacterial, antifungal, anticancer, antioxidants, antitubercular, antimalarial and anti-inflammatory. Due to lack of new antibiotics as well older antibiotic are rapidly proving ineffective, derivatives of triazine would be of great significance in future prospective.

TEICOPLANIN RESISTANCE IN GRAM-POSITIVE BACTERIAL ISOLATE: AN EMERGING THREAT

Objectives: Development of antimicrobial resistance in microorganism isolated from blood stream infection constitutes a major concern about their treatment. Teicoplanin is a glycopeptide antibiotic used in the treatment of infection caused by Gram-positive bacteria. This study was planned to determine Teicoplanin resistance in the Central India and recommend policy changes for prevention of the future resistance to the higher antibiotics. Methods: A total of 1855 septicemia suspected blood samples were studied. The blood culture samples were processed and identified in the microbiology laboratory according to the Clinical and Laboratory Standards Institute guidelines. Antibiotic susceptibility test was done using Kirby B disk diffusion method. Results: About 39.5% of blood culture samples showed positive growth for organism. We observed high teicoplanin resistance (29.5%) among Gram-positive isolates, predominantly (53%) in the Enterococcus species. Conclusion: Teicoplanin resistance has emerged tremendously in the present study. Hence, attention is required about this serious issue otherwise very limited choice of antibiotics will be available for treating infections in the future.

Identification of New Inhibitors for Klebsiella Pneumoniae Trimethoprim-Resistant Dihydrofolate Reductase: An in Silico Drug Repurposing Study

Klebsiella pneumoniae is a gram-negative, non-motile, rod-shaped, and pathogenic bacterium that is widely mutated and resistant to antibiotics. It can cause a wide range of hospital infections such as pneumonia, urinary tract infection, and blood-stream infection in humans. Identification and development of potential drugs due to high drug resistance by Klebsiella pneumoniae are inevitable. Dihydrofolate reductase is a vital enzyme for cells because it converts 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate. Trimethoprim (TMP) is an inhibitor of K. pneumoniae DHFR and other micro-organisms, but resistance to its action develops quickly when it is used. Identifying and designing new drugs is a costly, time-consuming, and challenging process. On the other hand, computational drug repurposing has become an efficient, economical and riskless strategy. In this study, the structure-based virtual docking approach was used to screen the FDA-approved drugs data-set against K. pneumoniae trimethoprim-resistance DHFR to identify potential hit compounds. Then, to validate the hit compounds, molecular dynamics simulations and MM/PBSA analyses were carried out. Our computational drug repurposing results show that the Olodaterol and Pazopanib like reference ligand interact with key residues such as Ile20, Glu27, Phe31, Met50, Leu53 and inhibit K. pneumoniae trimethoprim-resistant dihydrofolate reductase while TMP does not have strong interaction with the active site. According to the results of the current study and since it was based on drug repurposing both compounds of Pazopanib and Olodaterol could be evaluated in phase 2 clinical trials.