Antibiotic dispensing without a prescription poses a threat to public health as it leads to excessive antibiotic consumption. Inappropriate antibiotic availability to the community has been documented to be amongst drivers of antimicrobial resistance emergence. Community pharmacies are a source of antibiotics in low and middle-income countries (LMICs). We aimed at assessing antibiotic dispensing practices by community pharmacy retailers in Moshi urban, Kilimanjaro, Tanzania and recommend interventions to improve practice. Using a Simulated Client (SC) Method, an observational cross-sectional survey of antibiotic dispensing practices was conducted from 10th June to 10th July 2017. Data analysis was done using Stata 13 (StataCorp, College Station, TX, USA). A total of 82 pharmacies were visited. Part I pharmacies were 26 (31.71%) and 56 (68.29%) were part II. Overall 92.3% (95% CI 77.8–97.6) of retailers dispensed antibiotics without prescriptions. The antibiotics most commonly dispensed without a prescription were ampiclox for cough (3 encounters) and azithromycin for painful urination (3 encounters). An oral third generation cephalosporin (cefixime) was dispensed once for painful urination without prescription by a part I pharmacy retailer. Out of 21, 15(71.43%) prescriptions with incomplete doses were accepted and had antibiotics dispensed. Out of 68, 4(5.9%) retailers gave instructions for medicine use voluntarily. None of the retailers voluntarily explained drug side-effects. In Moshi pharmacies, a high proportion of antibiotics are sold and dispensed without prescriptions. Instructions for medicine use are rarely given and none of the retailers explain side effects. These findings support the need for a legislative enforcement of prescription-only antibiotic dispensing rules and regulations. Initiation of clinician and community antibiotic stewardship and educational programs on proper antibiotic use to both pharmacists and public by the regulatory bodies are highly needed.

BackgroundA high proportion of Extended-Spectrum-Beta-Lactamase (ESBL) producing Enterobacteriaceae is causing common infections in all regions of the world. The burden of antibiotic resistance due to ESBL in East Africa is large but information is scarce and thus it is unclear how big the problem really is. To gain insight into the magnitude and molecular epidemiology of ESBL-producing Enterobacteriaceae in East Africa a literature search was performed in PubMed on 31 July 2015 to retrieve articles with relevant information on ESBL.Methods and resultsMeta-analysis was performed to determine overall proportion estimate of ESBL-producing Enterobacteriaceae. A total of 4076 bacterial isolates were included in the analysis. The overall pooled proportion of ESBL-producing Enterobacteriaceae among included surveys done in East African hospitals was found to be 0.42 (95 % CI: 0.34–0.50). Heterogeneity (I2) between countries’ proportions in ESBL was significantly high (96.95 % and p < 0.001). The frequently detected genes encoding ESBL were CTX-M, TEM, SHV and OXA while the most infrequent reported genes were KPC and NDM.ConclusionThe available studies show a very wide variation in resistance due to ESBL between countries. This highlights a need for active surveillance systems which can help understand the actual epidemiology of ESBL, aid in formulating national or regional guidelines for proper screening of ESBL, and support developing standardized approaches for managing patients colonized with ESBL.Electronic supplementary materialThe online version of this article (doi:10.1186/s13756-016-0117-4) contains supplementary material, which is available to authorized users.

BackgroundPlasmodium falciparum resistance to anti-malarial drugs remains a major obstacle to the control of malaria. In 2001 Tanzania replaced chloroquine (CQ) with sulphadoxine-pyrimethamine (SP) as first-line drug, which in turn was replaced by artemisinin combination therapy in 2006. SP has however, continued to be used in intermittent preventive treatment of malaria in pregnancy (IPTp) despite reports of high levels of resistance to SP due to the lack of alternatives to SP for IPTp. Recent reports have indicated recovery of CQ-susceptibility in Malawi, Kenya, Mozambique, and Tanzania based on the prevalence of wild types at codon 76 of the Pfcrt gene in indigenous P. falciparum populations. The current prevalence of this Pfcrt-76 CQ resistance marker from six regions of Tanzania mainland is hereby reported.MethodsDNA extracted from filter-paper dried blood spots and rapid diagnostics kit strips collected from finger-prick blood were used to genotype the Pfcrt-76 resistance marker using PCR-RFLP. Data from previously published studies were used to generate CQ susceptibility recovery trends using logistic regression model.ResultsSeven hundred and forty one (741) samples were genotyped. The current frequency of the CQ-susceptible Pfcrt-K76 was above 92% and did not differ between regions in Tanzania (χ2 = 2.37; p = 0.795). The K76 allelic prevalence was between 85.7 and 93% in regions (χ2 = 7.88, p = 0.163). The CQ resistance recovery trends showed regional variability that may be caused by differences in malaria transmission intensity, but overall the trends converge as the susceptibility levels in all regions approach >90%.ConclusionsCQ withdrawal in Tanzania has resulted into >90% recovery of susceptibility in ten years of withdrawal. These findings are in support of the search for CQ-based combination drugs as a possible future alternative to SP for IPTp in places where full recovery of CQ-susceptibility will be evident.

BackgroundIn 2006, the first-line anti-malarial drug treatment in Tanzania was changed from sulphadoxine-pyrimethamine (SP) to artemether-lumefantrine (ALu), an artemisinin-based combination (ACT), since when the use of SP has been restricted for intermittent preventive treatment in pregnancy (IPTp). A number of Plasmodium falciparum mutations are known to be associated with resistance to SP, but it is not known if the prevalence of these mutations is increasing or decreasing under the conditions of reduced levels of SP use. This study reports on the current SP resistant quintuple Pfdhfr-Pfdhps mutations in six regions of Tanzania.MethodsFinger-prick blood on filter paper and rapid diagnostic test strips from P. falciparum-positive individuals of all age groups attending health facilities in six regions of Tanzania between June 2010 and August 2011 were obtained. Using chelex-100 extracted DNA, genotyping was done for mutations on codons 51, 59 and 108 of Pfdhfr and 437 and 540 of Pfdhps genes using PCR-RFLP technique.ResultsA total of 802 malaria-positive samples were screened and genotyped. The prevalence of Pfdhfr 51I, Pfdhps 437G and 540E varied between the regions (p < 0.001) whereas Pfdhfr 59R (FE 10.79, p = 0.225) and 108 N (FE 10.61, p = 0.239) did not vary between the regions. The Pfdhfr triple mutant was above 84% and close to fixation levels in all regions, whereas the Pfdhps double mutation ranged from 43.8 to 97% between the regions. The quintuple mutant (IRNGE) was the most prevalent in all regions and it varied significantly from 37.5 to 90.2% (χ2 = 1.11, p <0.001).ConclusionsThere is evidence of persistent high levels of SP resistance markers in Tanzania with evidence of quintuple mutations that are likely to become fixed in the population. This threatens the future of SP not only in IPTp programmes, but as a combination drug for ACT. Continuous monitoring of SP-IPTp efficacy should be encouraged subsequent to searching for alternative drugs for IPTp in East Africa.

Excessive use of antibiotics, especially watch group antibiotics such as ceftriaxone leads to emergence and spread of antimicrobial resistance (AMR). In low and middle-income countries (LMICs), antibiotics are overused but data on consumption is scarcely available. We aimed at determining the extent and predictors of ceftriaxone use in a tertiary care university teaching hospital in Kilimanjaro, Tanzania. A hospital-based cross-sectional study was conducted from August 2013 through August 2015. Patients admitted in the medical, surgical wards and their respective intensive care units, receiving antimicrobials and other medications for various ailments were enrolled. Socio-demographic and clinical data were recorded in a structured questionnaire from patients’ files and logistic regression was performed to determine the predictors for ceftriaxone use. Out of the 630 patients included in this study, 322 (51.1%) patients were on ceftriaxone during their time of hospitalization. Twenty-two patients out of 320 (6.9%) had been on ceftriaxone treatment without evidence of infection. Ceftriaxone use for surgical prophylaxis was 44 (40.7%), of which 32 (72.7%) and 9 (20.5%) received ceftriaxone prophylaxis before and after surgery, respectively. Three (6.8%) received ceftriaxone prophylaxis during surgery. Predicting factors for that the health facility administered ceftriaxone were identified as history of any medication use before referral to hospital [OR = 3.4, 95% CI (1.0–11.4), p = 0.047], bacterial infection [OR = 18.0, 95% CI (1.4–225.7, p = 0.025)], surgical ward [OR = 2.9, 95% CI (0.9–9.4), p = 0.078] and medical wards [OR = 5.0, 95% CI (0.9–28.3), p = 0.070]. Overall, a high ceftriaxone use at KCMC hospital was observed. Antimicrobial stewardship programs are highly needed to monitor and regulate hospital antimicrobial consumption, which in turn could help in halting the rising crisis of antimicrobial resistance.

BackgroundLimited information regarding the clonality of circulating E. coli strains in tertiary care hospitals in low and middle-income countries is available. The purpose of this study was to determine the serotypes, antimicrobial resistance and virulence genes. Further, we carried out a phylogenetic tree reconstruction to determine relatedness of E. coli isolated from patients in a tertiary care hospital in Tanzania.MethodsE. coli isolates from inpatients admitted at Kilimanjaro Christian Medical Centre between August 2013 and August 2015 were fully genome-sequenced at KCMC hospital. Sequence analysis was done for identification of resistance genes, Multi-Locus Sequence Typing, serotyping, and virulence genes. Phylogeny reconstruction using CSI Phylogeny was done to ascertain E. coli relatedness. Stata 13 (College Station, Texas 77,845 USA) was used to determine Cohen’s kappa coefficient of agreement between the phenotypically tested and whole genome sequence predicted antimicrobial resistance.ResultsOut of 38 E. coli isolates, 21 different sequence types (ST) were observed. Eight (21.1%) isolates belonged to ST131; of which 7 (87.5.%) were serotype O25:H4. Ten (18.4%) isolates belonged to ST10 clonal complex; of these, four (40.0%) were ST617 with serotype O89:H10. Twenty-eight (73.7%) isolates carried genes encoding beta-lactam resistance enzymes. On average, agreement across all drugs tested was 83.9%. Trimethoprim/sulphamethoxazole (co-trimoxazole) showed moderate agreement: 45.8%, kappa =15% and p = 0.08. Amoxicillin-clavulanate showed strongest agreement: 87.5%, kappa = 74% and p = 0.0001. Twenty-two (57.9%) isolates carried virulence factors for host cells adherence and 25 (65.7%) for factors that promote E. coli immune evasion by increasing survival in serum. The phylogeny analysis showed that ST131 clustering close together whereas ST10 clonal complex had a very clear segregation of the ST617 and a mix of the rest STs.ConclusionThere is a high diversity of E. coli isolated from patients admitted to a tertiary care hospital in Tanzania. This underscores the necessity to routinely screen all bacterial isolates of clinical importance in tertiary health care facilities. WGS use for laboratory-based surveillance can be an effective early warning system for emerging pathogens and resistance mechanisms in LMICs.Electronic supplementary materialThe online version of this article (10.1186/s13756-018-0361-x) contains supplementary material, which is available to authorized users.

Emergence and spread of extended spectrum beta-lactamase (ESBL)-producing gram-negative bacteria, mainly due to CTX-M, is a major global public health problem. Patients infected with ESBL-producing gram-negative bacteria have an increased risk of treatment failure and death. We investigated the prevalence and risk factors for CTX-M gram-negative bacteria isolated from clinical specimens of patients hospitalized at a tertiary care hospital in Kilimanjaro, Tanzania. Isolated gram-negative bacteria from inpatients admitted at Kilimanjaro Christian Medical Centre (KCMC) between August 2013 and August 2015 were fully genome sequenced. The prevalence of ESBL-producing gram-negative bacteria was determined based on the presence of blaCTX-M. The odds ratio (OR) and risk factors for ESBL-producing gram-negative bacteria due to CTX-M were assessed using logistic regression models. The overall CTX-M prevalence (95% CI) was 13.6% (10.1–18.1). Adjusted for other factors, the OR of CTX-M gram-negative bacteria for patients previously hospitalized was 0.26 (0.08–0.88), p = 0.031; the OR for patients currently on antibiotics was 4.02 (1.29–12.58), p = 0.017; the OR for patients currently on ceftriaxone was 0.14 (0.04–0.46), p = 0.001; and the OR for patients with wound infections was 0.24 (0.09–0.61), p = 0.003. The prevalence of ESBL-producing gram-negative bacteria due to CTX-M in this setting is relatively low compared to other previous reports in similar settings. However, to properly stop further spread in the hospital, we recommend setting up a hospital surveillance system that takes full advantage of the available next-generation sequencing facility to routinely screen for all types of bacterial resistance genes.

This study aimed to use whole-genome sequencing to determine virulence and antimicrobial resistance genes in K. pneumoniae isolated from patients in a tertiary care hospital in Kilimanjaro. K. pneumoniae isolates from patients attending Kilimanjaro Christian Medical Centre between August 2013 and August 2015 were fully genome-sequenced and analysed locally. Sequence analysis was done for identification of virulence and AMR genes. Plasmid and multi-locus sequence typing and capsular or capsular (K) typing were performed and phylogeny was done to ascertain K. pneumoniae relatedness. Stata 13 (College Station, TX, 77845, USA) was used to determine Cohen's kappa coefficient of agreement between the phenotypically tested and sequence-predicted resistance. A total of 16 (47.1%) sequence types (STs) and 10 (29.4%) K types were identified in 30 (88.2%) and 17 (50.0%) of all analysed isolates, respectively. K. pneumoniae ST17 were 6 (17.6%). The commonest determinants were bla in 16 (47.1%) isolates bla in 30 (88.2%), bla in 8 (23.5%) and bla in 18 (52.9%) isolates. Resistance genes for aminoglycosides were detected in 21 (61.8%) isolates, fluoroquinolones in 13 (38.2%) and quinolones 34 (100%). Ceftazidime and ceftriaxone showed the strongest agreement between phenotype- and sequence-based resistance results: 93.8%, kappa = 0.87 and p = 0.0002. Yersiniabactin determinant was detected in 12 (35.3%) of K. pneumoniae. The proportion of AMR and virulence determinants detected in K. pneumoniae is alarming. WGS-based diagnostic approach has showed promising potentials in clinical microbiology, hospital outbreak source tracing virulence and AMR detection at KCMC.