Fluoroquinolone resistance among fecal extended spectrum ßeta lactamases positive Enterobacterales isolates from children in Dar es Salaam, Tanzania.

BACKGROUND: Fluoroquinolones have been, and continue to be, routinely used for treatment of many bacterial infections. In recent years, most parts of the world have reported an increasing trend of fluoroquinolone resistant (FQR) Gram-negative bacteria. METHODS: A cross-sectional study was conducted between March 2017 and July 2018 among children admitted due to fever to referral hospitals in Dar es Salaam, Tanzania. Rectal swabs were used to screen for carriage of extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE). ESBL-PE isolates were tested for quinolone resistance by disk diffusion method. Randomly selected fluroquinolone resistant isolates were characterized by using whole genome sequencing. RESULTS: A total of 142 ESBL-PE archived isolates were tested for fluoroquinolone resistance. Overall phenotypic resistance to ciprofloxacin, levofloxacin and moxifloxacin was found in 68% (97/142). The highest resistance rate was seen among Citrobacter spp. (100%, 5/5), followed by Klebsiella. pneumoniae (76.1%; 35/46), Escherichia coli (65.6%; 42/64) and Enterobacter spp. (31.9%; 15/47). Whole genome sequencing (WGS) was performed on 42 fluoroquinolone resistant-ESBL producing isolates and revealed that 38/42; or 90.5%, of the isolates carried one or more plasmid mediated quinolone resistance (PMQR) genes. The most frequent PMQR genes were aac(6')-lb-cr (74%; 31/42), followed by qnrB1 (40%; 17/42), oqx, qnrB6 and qnS1. Chromosomal mutations in gyrA, parC and parE were detected among 19/42 isolates, and all were in E. coli. Most of the E. coli isolates (17/20) had high MIC values of > 32 µg/ml for fluoroquinolones. In these strains, multiple chromosomal mutations were detected, and all except three strains had additional PMQR genes. Sequence types, ST131 and ST617 predominated among E. coli isolates, while ST607 was more common out of 12 sequence types detected among the K. pneumoniae. Fluoroquinolone resistance genes were mostly associated with the IncF plasmids. CONCLUSION: The ESBL-PE isolates showed high rates of phenotypic resistance towards fluoroquinolones likely mediated by both chromosomal mutations and PMQR genes. Chromosomal mutations with or without the presence of PMQR were associated with high MIC values in these bacteria strains. We also found a diversity of PMQR genes, sequence types, virulence genes, and plasmid located antimicrobial resistance (AMR) genes towards other antimicrobial agents.

Profiling of antimicrobial dispensing practices in accredited drug dispensing outlets in Tanzania: a mixed-method cross-sectional study focusing on pediatric patients.

BACKGROUND: The emergency of antimicrobial resistance due to irrational antimicrobial use has put public health under threat. Accredited Drug Dispensing Outlets (ADDOs) play an important role in enhancing availability and accessibility of antimicrobials, however, there is a scarcity of studies assessing antimicrobial dispensing practices in these outlets, focusing on children in Tanzania. OBJECTIVE: This study was conducted to assess the antimicrobial dispensing practices among ADDO dispensers and explore the factors influencing the use of antimicrobials for children in Tanzania. METHODS: A community-based cross-sectional study utilizing both qualitative (interviews) and quantitative (simulated clients) methods was conducted between June and September 2020 in seven zones and 14 regions in Tanzania. RESULTS: The study found inappropriate dispensing and use of antimicrobials for children, influenced by multiple factors such as patient's and dispenser's knowledge and attitude, financial constraints, and product-related factors. Only 8% (62/773) of dispensers asked for prescriptions, while the majority (90%) were willing to dispense without prescriptions. Most dispensers, 83% (426/513), supplied incomplete doses of antimicrobials and only 60.5% (345/570) of the dispensers gave proper instructions for antimicrobial use to clients. Over 75% of ADDO dispensers displayed poor practice in taking patient history. CONCLUSION: ADDO dispensers demonstrated poor practices in dispensing and promoting rational antimicrobial use for children. Training, support, and regulatory interventions are required to improve antimicrobial dispensing practices in community drug outlets.

High fecal carriage of extended Beta Lactamase producing Enterobacteriaceae among adult patients admitted in referral hospitals in Dar es Salaam, Tanzania.

BACKGROUND: Multi-drug resistance pathogens such as Extended-Spectrum Beta-Lactamase (ESBL) producing Enterobacteriaceae (ESBL-PE) are of great global health concern, since they are associated with increased morbidity and mortality. Even in the absence of infections caused by these pathogens, colonization is a great threat and can lead to cross transfer among hospitalized patients. To date data on carriage of these pathogens is still limited in Tanzania. Therefore, this study aimed to determine ESBL-PE fecal carriage rate and associated factors among hospitalized patients at Referral hospitals in Dar es Salaam. METHODS: This was a cross sectional study conducted from May to July 2017 among patients admitted in three referral hospitals in Dar es Salaam, Tanzania. Rectal swabs were collected and screened for ESBL production using MacConkey agar supplemented with Ceftazidime 2 µg/ml. Phenotypic confirmation of ESBL-PE was done by double disk diffusion method. Statistical analysis was performed using Statistical Package for Social Sciences (SPPS) software version 20. RESULTS: Of the 196 enrolled participants, 59.7% (117/196) were confirmed to carry ESBL-PE. Diarrheic patients (57/79) had statistically significant high prevalence of ESBL colonization compared to those without diarrhea (60/117) (p = 0.01). A total of 131 ESBL-PE were isolated from 117 patients, whereby, Escherichia coli accounted for 68.7%, Klebsiella pneumoniae 28.2% and Citrobacter species 0.8%. ESBL-PE carriage was significantly higher in patients with diarrhea compared to those without diarrhea (72% vs 53.1%, p = 0.01). Recent antibiotic use was independently associated with carriage of ESBL-PE (aOR 14.65, 95%CI 3.07-69.88, p = 0.01). CONCLUSIONS: High prevalence of fecal carriage of ESBL-PE was observed in patients admitted in tertiary hospitals in Dar es Salaam, Tanzania. The use of antibiotics was associated with carriage of ESBL producers among the study population.

Implementation research for promoting access and rational use of antibiotics for children: lessons learnt from Tanzania.

Implementation research (IR) has proved to be a potential catalyst in facilitating the uptake of evidence-based innovations into routine practices and thereby maximizing public health outcomes. IR not only focuses on the effectiveness of the innovations but also identifies and addresses the barriers and facilitators to maximize their uptake into routine practices. This article describes the processes undertaken to implement a research project aimed at promoting access and rational use of antibiotics for children (PARAC). It also provides an overview of the lessons learnt during its implementation in Tanzanian hospital and community settings.

Seroprevalence and risk factors of Toxoplasmosis among HIV infected women of child-bearing age attending care and treatment clinics in Dar es Salaam, Tanzania.

Background: Toxoplasmosis in HIV-infected women of child-bearing age (HIV-WCB) increases the risk for congenital toxoplasmosis, leading to many complications. However, its magnitude is unknown in this population. Objectives: The study aimed to determine the prevalence and factors associated with toxoplasmosis among HIV-WCB. Methods: This was a cross-sectional study conducted from July to August 2020 among HIV- WCB attending care and treatment clinic (CTC) at Muhimbili National Hospital and Mnazi Mmoja hospital. Questionnaire and TORCH rapid test were used to obtain data and serological testing respectively. Data analysis was done using statistical package for social sciences (SPSS) version 20. Results: Overall, 29.7% of the study participants were positive for anti-T. gondii IgG, whereas none tested positive for IgM. Multivariate analysis showed that the probability of being infected with T. gondii increased by 57.1% for participants who consumed raw vegetables (p=0.005, aOR=0.43, 95%CI = 1.24-8.77). Other common risk factors such as undercooked meat consumption, source of drinking water, and cat ownership at home showed no association. Conclusion: A high number of HIV-WCB have not developed immunity to T. gondii in the study area. Introduction of routine screening during antenatal visits for pregnant women and further epidemiological studies are warranted in the country.

Predictors of Surgical Site Infections among Patients Undergoing Open Urological Surgery at a Tertiary Hospital, Tanzania: A Cross Sectional Study.

Background: Surgical Site Infection (SSI) is one of the major hospital acquired infections, highly associated with prolonged hospitalisation, morbidity and mortality. In open urological surgeries, little is known on magnitude and factors associated with development of SSI. Methods and Materials: The intervention was a cross-sectional prospective observational study performed between August 2015 and March 2016 at Muhimbili National hospital (MNH), Dar es Salaam, Tanzania. Patients who underwent open urological surgery at MNH during the study period and met inclusion criteria were consecutively enrolled, and followed up for 30 days. Patients' and operative characteristics were recorded using standard structured questionnaires. Wound/pus swabs were collected from patients with clinical evidence of SSI for bacteriological processing. Data analysis was performed using SPSS version 20. Results: Of 182 patients who underwent open urological surgery, 22% (40/182) developed SSI. Pre-operative urinary tract infection (aOR 9.73, 95%CI 3.93-24.09, p<.001) and contaminated wound class (aOR 24.997, 95%CI 2.58-242.42, p = .005) were independent predictors for development of SSI. Shaving within 30 hrs before surgical procedure was found to be protective for developing SSI (aOR 0.26, 95%CI 0.09-0.79, p=.02). Escherichia coli (20/40) was the most predominant pathogen in SSI followed by Klebsiella pneumoniae (7/40) and S. aureus (6/40). Gram-negative bacteria were highly resistant to ceftriaxone, gentamicin, amoxicillin-clavulanic acid and trimethoprimsulfamethoxazole. Conclusion: Surgical Site Infection was high in open urological interventions. Pre-operative urinary tract infection and contaminated wound class predicted SSI. Bacteria causing SSI were highly resistant to commonly used antibiotics.

Gastrointestinal colonization of extended-spectrum beta-lactamase-producing bacteria among children below five years of age hospitalized with fever in Dar es Salaam, Tanzania.

OBJECTIVES: Gastrointestinal colonization of extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE) is of concern because prior colonization increases risk for subsequent infections. To date, the link between ESBL-PE faecal carriage and the risk of subsequent ESBL-PE infection has not been well established, and information on carriage of such pathogens among children with invasive infections such as bloodstream infections (BSI) remains to be explored worldwide. METHODS: This cross-sectional study was conducted among children under the age of 5 years admitted for febrile illness in Dar es Salaam, Tanzania, between March 2017 and July 2018. We used rectal swabs to screen for ESBL-PE using selective media, ChromID ESBL. Bacterial isolates were identified by MALDI-TOF. Blood cultures were drawn from all children. Antimicrobial susceptibility testing was done using a disk diffusion method. ESBL alleles were identified by real-time PCR and sequencing. RESULTS: The overall prevalence of ESBL-PE carriage was 56% (112/200) and was highest among children 4 to 6 months old (17/21, 81%) (P = 0.05). Children with BSI had high ESBL-PE carriage (78.4%) compared to those without BSI (53.1%) (P = 0.02; aOR 3.4, 95% confidence interval 1.20-9.58). The most common isolate was E. coli (64/112, 45%). Sixteen pairs of ESBL-PE isolates (from the gut and from blood) had a similar antimicrobial susceptibility profile. We detected blaCTX-M gene in 97% of all phenotypically detected ESBL-PE; among those, blaCTX-M-15 was dominant (99%). CONCLUSION: We report a high prevalence of ESBL-PE faecal carriage among children with BSI in Tanzania. Colonization of ESBL-PE was a risk factor for ESBL-BSI.

Implementation of antibiotic stewardship programmes in paediatric patients in regional referral hospitals in Tanzania: experience from prescribers and dispensers.

Background: In 2017, Tanzania launched the National Action Plan for Antimicrobial Resistance (NAPAR), 2017-2022 and implementation of antibiotic stewardship programmes (ASPs) was one of the agendas. Since the launch of the National Action Plan, no study has been done to assess its implementation. Objectives: To explore the experiences of prescribers and dispensers on implementing ASPs among paediatric patients attending Regional Referral Hospitals (RRHs) in Tanzania. Methods: An exploratory qualitative study was conducted among key informants, in 14 RRHs in Tanzania between July and August 2020. A total of 28 key informants, 14 dispensers in charge of pharmacies and 14 medical doctors in charge of paediatric departments (prescribers), were interviewed. A hybrid thematic analysis was conducted on the gathered information. Results: Most of the study participants were not conversant with the term 'antibiotic stewardship'. Some had heard about the programmes but were not aware of the activities involved in the programme. Those who were knowledgeable on ASPs mentioned the lack of existence of such programmes in their settings. They further added that absence or limited knowledge of the stewardship concepts may have influenced the current poor practices. Barriers to the implementation of ASPs mentioned were lack of laboratory facilities to support culture and susceptibility tests, lack of materials and reagents, management pressure to prevent loss or to generate income, patients' influence and limited training opportunities. Conclusions: Despite launching the NAPAR in 2017, we found limited implementation of ASPs in the management of paediatric patients. This study highlighted some barriers and identified possible intervention points.

Fecal carriage and factors associated with extended-spectrum ß-lactamase-producing Enterobacteriaceae among pregnant women at the tertiary referral hospital, Tanzania.

BACKGROUND: Infections due to extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) are increasing worldwide. Evidence indicates that fecal carriage of ESBL-E in pregnancy predisposes women to potential life-threatening urinary tract infections and subsequently increasing the risk of neonatal infections. There is limited data regarding fecal carriage of ESBL-E and associated factors among pregnant women in Tanzania. We aimed to address the gap by determining the proportion of pregnant women with ESBL-E fecal carriage and identify the related factors. METHODOLOGY: A hospital-based cross-sectional study was conducted at Muhimbili National Hospital in Dar es Salaam, Tanzania. A total of 182 pregnant women at the gestational age of 37 weeks and above were enrolled. Participants' socio-demographic, clinical, and hygienic information were collected by using a well-structured questionnaire. Rectal swabs were collected and processed for isolation of ESBL-E. The extended-spectrum ß-lactamase production and antibiotic susceptibility test (AST) were performed using a double-disc synergy test and Kirby-Bauer disc diffusion method, respectively. RESULTS: A total of 117 (64.3%) pregnant women were found to carry ESBL-E. Factors such as self-prescription of antibiotic medication during pregnancy, low education level, and toilet sharing were independently associated with ESBL-E fecal carriage. Five ESBL-E species that were isolated include Escherichia coli (84.6%), Klebsiella pneumoniae (8.9%), Klebsiella oxytoca (3.3%), Citrobacter spp. (1.6%), and Enterobacter spp. (1.6%). ESBL-E isolates demonstrated high resistance to aztreonam and sulphamethoxazole-trimethoprim. CONCLUSION: This study has revealed a relatively high fecal carriage of ESBL-E among pregnant women, suggesting that there is a need for routine screening among that population. We recommend further studies to explore comprehensively the factors associated with high fecal carriage of ESBL-E in pregnancy and the potential transmission kinetics to their newborn babies.