In vitro activity of cefepime against extended spectrum β-lactamase- producing Escherichia coli and Klebsiella pneumoniae from clinical specimens at Bugando Medical Centre, Mwanza, Tanzania

There is an increase in isolation of extended spectrum beta-lactamase (ESBL) producing isolates from clinical samples worldwide. In developing countries the treatment option of ESBL producing isolates is limited. Recently fourth generation cephalosporins have been introduced for use in Tanzania. This study was done to determine in vitro activity of cefepime against ESBL producing clinical isolates. Disc diffusion testing was performed to 235 ESBL producing isolates; of which 73 (31%) were Escherichia coli and 162 (69%) Klebsiella pneumoniae. The sensitivity rate of E. coli and K. pneumoniae to cefepime were 15.1% and 4.3%, respectively (P=0.012); intermediate sensitivity rate was observed in 13.7% for E. coli and 19.8% for K. pneumoniae. The mean zones of inhibition diameter among sensitive isolates were 24.9mm and 20.0mm for E. coli and K. pneumonia, respectively (P=0.0085). Cefepime is less active against ESBL producing organisms; hence the use of this drug should be guided using local resistance profile

High Prevalence of Non-Typhoid Salmonella Bacteraemia Among Febrile HIV Adult Patients Admitted at a Tertiary Hospital, North-Western Tanzania.

Bacterial blood stream infections constitute a significant public-health problem and it is an important cause of morbidity and mortality in HIV infected patients. Little is known in developing countries regarding salmonella bacteraemia among HIV patients. The purpose of this study was to determine the bacterial pathogens causing blood stream infection among febrile adults attending in a tertiary hospital North-Western, Tanzania. A prospective cross-sectional study involving 346 consecutive, febrile adult patients admitted at Bugando Medical Centre was conducted. Demographic and other data were collected using standardized questionnaires. Blood culture was done followed by susceptibility testing using disc diffusion method. HIV testing was also performed as per Tanzania national algorithm and total white blood cell counts and CD4+ counts determined. Of 346 febrile adult patients 33 (9.5%) had blood stream infections. The common isolates were Salmonella spp 13(39.4%), Escherichia coli 8 (24.2%), Streptococcus pneumonia 5(15.2%), Staphylococcus aureus 4(12.1%), Citrobacter spp 1(3%), Streptococcus pyogenes 1(3%) and Klebsiella pneumonia 1(3%). A total of 156 (45.1%) patients were HIV infected; of whom 12/156 (7.6%) were infected by non-typhoid Salmonella spp compared to 1/190 (0.5%) of non-HIV infected patients (RRR 11.2, p=0.029) infected with Salmonella typhi. HIV infected patients with bacteraemia had significantly lower CD4+ count than those without bacteraemia (median 28 vs. 88 cells/ml, p=0.01). Patients with salmonella bacteraemia had significantly lower median of WBC than those with non-salmonella as well as those without bacteraemia (median, 3.6 vs. 17.5 vs. 9.8x109, p=0.0001). All Salmonella spp were sensitive to ceftriaxone and imipenem, while being 84%, 69.2%, 38% and 8% resistant to chloramphenicol, ampicillin, sulphamethaxazole/trimethoprim and ciprofloxacin respectively. Predictors of mortality were HIV infection (OR 2.3, p=0.006), Glasgow coma score of less than 15 (OR 3.4, p=0.0001) and night sweats (OR 2.4, p=0.014). Non-typhoid Salmonella spp that are highly resistant to common antibiotics are predominant cause of bacterial blood stream infection among HIV patients attending Bugando Medical Centre. Continuous surveillance and intervention strategies should be put in place to monitor and manage cases of bloodstream infections in HIV-positive patients in Mwanza, Tanzania

High Prevalence of Tuberculosis among Adults with Fever Admitted at a Tertiary Hospital in North-western Tanzania

Tuberculosis is a leading cause of death in developing countries where HIV is endemic. This hospital based study was done to estimate the magnitude of pulmonary and extra-pulmonary tuberculosis and to determine predictors of tuberculosis among febrile adults admitted at Bugando Medical Centre (BMC), Mwanza, Tanzania. A total of 346 adults febrile patients admitted in medical wards were studied. Sputum for AFB microscopy and chest X-rays was used to diagnose tuberculosis. Clinical features were collected using standardized data collection tool. HIV testing and CD4 counts were determined. Data were analyzed using STATA version 11 software. Of 346 febrile adults patients 116 (33.5%) were diagnosed to have tuberculosis; of which 79 (68.1%) and 37 (31.9%) had pulmonary tuberculosis (PTB) and extra-pulmonary tuberculosis, respectively. Smear negative PTB were more common in HIV positive than in HIV negative patients (50% vs. 18.5%, p=0.007). Extra-pulmonary tuberculosis was more common in HIV positive patients than pulmonary tuberculosis (86.4% vs. 13.6%), p=0.0001). On multivariate logistic regression analysis the predictors of tuberculosis were; age above 35 years (OR =2.38, p=0.007), cardinal symptoms (OR=37, p<0.0001), pleural effusion (OR=24, p=0.0001), and HIV status (OR =3.2, p=0.0001). Of 79 patients with PTB, 48 (60.7%) were AFB smear positive and 31(39.3%) were AFB smear negative. HIV patients with smear negative tuberculosis had significantly lower CD4 count than HIV patients with smear positive tuberculosis (63.5 cells/μl versus 111.5 cells/μl) [Mann- Whitney test p=0.0431]]. No different in mortality was observed between patients with TB and those without TB admitted in BMC medical wards (28.5% vs. 23.0%, p= 0.1318). Tuberculosis is the commonest cause of fever among adults patients admitted at BMC and is predicted by age above 35 years, positive HIV status, cardinal PTB symptoms, and pleural effusion. Routinely TB screening is highly recommended among adults with fever, cough, night sweating and wasting in countries where HIV is endemic.\u

Predominance of Methicillin Resistant Staphylococcus Aureus -ST88 and New ST1797 causing Wound Infection and Abscesses.

Although there has been a worldwide emergence and spread of methicillin-resistant Staphylococcus aureus (MRSA), little is known about the molecular epidemiology of MRSA in Tanzania. In this study, we characterized MRSA strains isolated from clinical specimens at the Bugando Medical Centre, Tanzania, between January and December 2008. Of 160 S. aureus isolates from 600 clinical specimens, 24 (15%) were found to be MRSA. Besides molecular screening for the Panton Valentine leukocidin (PVL) genes by PCR, MRSA strains were further characterized by Multi-Locus Sequence Typing (MLST) and spa typing. Despite considerable genetic diversity, the spa types t690 (29.1%) and t7231 (41.6%), as well as the sequence types (ST) 88 (54.2%) and 1797 (29.1%), were dominant among clinical isolates. The PVL genes were detected in 4 isolates; of these, 3 were found in ST 88 and one in ST1820. Resistance to erythromycin, clindamicin, gentamicin, tetracycline and co-trimoxazole was found in 45.8%, 62.5%, 41.6%, 45.8% and 50% of the strains, respectively. We present the first thorough typing of MRSA at a Tanzanian hospital.  Despite considerable genetic diversity, ST88 was dominant among clinical isolates at the Bugando Medical Centre. Active and standardized surveillance of nosocomial MRSA infection should be conducted in the future to analyse the infection and transmission rates and implement effective control measures

Therapeutic Efficacy of Sulfadoxine-Pyrimethamine and Prevalence of Resistance Markers in Tanzania Prior to Revision of Malaria Treatment Policy: Plasmodium Falciparum Dihydrofolate Reductase and Dihydropteroate Synthase Mutations in Monitoring in Vivo Resistance.

Prior to the 2001 malarial treatment policy change in Tanzania, we conducted trials to assess the efficacy of sulfadoxine-pyrimethamine (SP) and the usefulness of molecular markers in monitoring resistance. A total of 383 uncomplicated Plasmodium falciparum malaria patients (between 6 and 59 months old) were treated with SP and their responses were assessed. Mutations in the P. falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes in admission day blood samples were analyzed. Results indicated that 85.6% of the patients showed an adequate clinical response, 9.7% an early treatment failure, and 4.7% a late treatment failure. The quintuple mutant genotype (pfdhfr 51 Ile, 59 Arg, and 108 Asn and pfdhps 437 Gly and 540 Glu) showed an association with treatment outcome (odds ratio = 2.1; 95% confidence interval = 0.94-4.48, P = 0.045). The prevalence of the triple pfdhfr mutant genotype (51 Ile, 59 Arg, and 108 Asn) at a site of high SP resistance (23.6%) was four times higher compared with that observed at sites of moderate SP resistance (6.8-14.4%) (P = 0.000001). The genotype failure index calculated by using this marker was invariable (1.96-2.1) at sites with moderate SP resistance, but varied (3.4) at a site of high SP resistance. In conclusion, our clinical and molecular findings suggest that SP may have a short useful therapeutic life in Tanzania; thus, its adoption as an interim first-line antimalarial drug. The findings also point to the potential of the triple pfdhfr mutant genotype as an early warning tool for increasing SP resistance. These data form the baseline SP efficacy and molecular markers profile in Tanzania prior to the policy change

Hypertension, kidney disease, HIV and antiretroviral therapy among Tanzanian adults: a cross-sectional study.

BACKGROUND: The epidemics of HIV and hypertension are converging in sub-Saharan Africa. Due to antiretroviral therapy (ART), more HIV-infected adults are living longer and gaining weight, putting them at greater risk for hypertension and kidney disease. The relationship between hypertension, kidney disease and long-term ART among African adults, though, remains poorly defined. Therefore, we determined the prevalences of hypertension and kidney disease in HIV-infected adults (ART-naive and on ART >2 years) compared to HIV-negative adults. We hypothesized that there would be a higher hypertension prevalence among HIV-infected adults on ART, even after adjusting for age and adiposity. METHODS: In this cross-sectional study conducted between October 2012 and April 2013, consecutive adults (>18 years old) attending an HIV clinic in Tanzania were enrolled in three groups: 1) HIV-negative controls, 2) HIV-infected, ART-naive, and 3) HIV-infected on ART for >2 years. The main study outcomes were hypertension and kidney disease (both defined by international guidelines). We compared hypertension prevalence between each HIV group versus the control group by Fisher's exact test. Logistic regression was used to determine if differences in hypertension prevalence were fully explained by confounding. RESULTS: Among HIV-negative adults, 25/153 (16.3%) had hypertension (similar to recent community survey data). HIV-infected adults on ART had a higher prevalence of hypertension (43/150 (28.7%), P = 0.01) and a higher odds of hypertension even after adjustment (odds ratio (OR) = 2.19 (1.18 to 4.05), P = 0.01 in the best model). HIV-infected, ART-naive adults had a lower prevalence of hypertension (8/151 (5.3%), P = 0.003) and a lower odds of hypertension after adjustment (OR= 0.35 (0.15 to 0.84), P = 0.02 in the best model). Awareness of hypertension was ≤ 25% among hypertensive adults in all three groups. Kidney disease was common in all three groups (25.6% to 41.3%) and strongly associated with hypertension (P 2 years had two-fold greater odds of hypertension than HIV-negative controls. HIV-infected adults with hypertension were rarely aware of their diagnosis but often have evidence of kidney disease. Intensive hypertension screening and education are needed in HIV-clinics in sub-Saharan Africa. Further studies should determine if chronic, dysregulated inflammation may accelerate hypertension in this population

Short-term and long-term cardiovascular risk, metabolic syndrome and HIV in Tanzania.

OBJECTIVE: To compare short-term and long-term cardiovascular disease (CVD) risk scores and prevalence of metabolic syndrome in HIV-infected adults receiving and not receiving antiretroviral therapy (ART) to HIV-negative controls. METHODS: A cross-sectional study including 151 HIV-infected, ART-naive, 150 HIV-infected on ART and 153 HIV-negative adults. Traditional cardiovascular risk factors were determined by standard investigations. The primary outcome was American College of Cardiology/American Heart Association Atherosclerotic CVD (ASCVD) Risk Estimator lifetime CVD risk score. Secondary outcomes were ASCVD 10-year risk, Framingham risk scores, statin indication and metabolic syndrome. RESULTS: Compared with HIV-negative controls, more HIV-infected adults on ART were classified as high lifetime CVD risk (34.7% vs 17.0%, p<0.001) although 10-year risk scores were similar, a trend which was similar across multiple CVD risk models. In addition, HIV-infected adults on ART had a higher prevalence of metabolic syndrome versus HIV-negative controls (21.3% vs 7.8%, p=0.008), with two common clusters of risk factors. More than one-quarter (28.7%) of HIV-infected Tanzanian adults on ART meet criteria for statin initiation. CONCLUSIONS: HIV-infected ART-treated individuals have high lifetime cardiovascular risk, and this risk seems to develop rapidly in the first 3-4 years of ART as does the development of clusters of metabolic syndrome criteria. These data identify a new subgroup of low short-term/high-lifetime risk HIV-infected individuals on ART who do not currently meet criteria for CVD risk factor modification but require further study

Surgical management of Diabetic foot ulcers: A Tanzanian university teaching hospital experience

\ud \ud Diabetic foot ulcers (DFUs) pose a therapeutic challenge to surgeons, especially in developing countries where health care resources are limited and the vast majority of patients present to health facilities late with advanced foot ulcers. A prospective descriptive study was done at Bugando Medical Centre from February 2008 to January 2010 to describe our experience in the surgical management of DFUs in our local environment and compare with what is known in the literature. Of the total 4238 diabetic patients seen at BMC during the period under study, 136 (3.2%) patients had DFUs. Males outnumbered females by the ratio of 1.2:1. Their mean age was 54.32 years (ranged 21-72years). Thirty-eight (27.9%) patients were newly diagnosed diabetic patients. The majority of patients (95.5%) had type 2 diabetes mellitus. The mean duration of diabetes was 8.2 years while the duration of DFUs was 18.34 weeks. Fourteen (10.3%) patients had previous history of foot ulcers and six (4.4%) patients had previous amputations. The forefoot was commonly affected in 60.3% of cases. Neuropathic ulcers were the most common type of DFUs in 57.4% of cases. Wagner's stage 4 and 5 ulcers were the most prevalent at 29.4% and 23.5% respectively. The majority of patients (72.1%) were treated surgically. Lower limb amputation was the most common surgical procedure performed in 56.7% of cases. The complication rate was (33.5%) and surgical site infection was the most common complication (18.8%). Bacterial profile revealed polymicrobial pattern and Staphylococcus aureus was the most frequent microorganism isolated. All the microorganisms isolated showed high resistance to commonly used antibiotics except for Meropenem and imipenem, which were 100% sensitive each respectively. The mean hospital stay was 36.24 ± 12.62 days (ranged 18-128 days). Mortality rate was 13.2%. Diabetic foot ulceration constitutes a major source of morbidity and mortality among patients with diabetes mellitus at Bugando Medical Centre and is the leading cause of non-traumatic lower limb amputation. A multidisciplinary team approach targeting at good glycaemic control, education on foot care and appropriate footware, control of infection and early surgical intervention is required in order to reduce the morbidity and mortality associated with DFUs. Due to polymicrobial infection and antibiotic resistance, surgical intervention must be concerned

In vitro activity of cefepime against extended spectrum β-lactamase- producing Escherichia coli and Klebsiella pneumoniae from clinical specimens at Bugando Medical Centre, Mwanza, Tanzania

There is an increase in isolation of extended spectrum beta-lactamase (ESBL) producing isolates from clinical samples worldwide. In developing countries the treatment option of ESBL producing isolates is limited. Recently fourth generation cephalosporins have been introduced for use in Tanzania. This study was done to determine in vitro activity of cefepime against ESBL producing clinical isolates. Disc diffusion testing was performed to 235 ESBL producing isolates; of which 73 (31%) were Escherichia coli and 162 (69%) Klebsiella pneumoniae . The sensitivity rate of E. coli and K. pneumoniae to cefepime were 15.1% and 4.3%, respectively (P=0.012); intermediate sensitivity rate was observed in 13.7% for E. coli and 19.8% for K. pneumoniae. The mean zones of inhibition diameter among sensitive isolates were 24.9mm and 20.0mm for E. coli and K. pneumonia, respectively (P=0.0085). Cefepime is less active against ESBL producing organisms; hence the use of this drug should be guided using local resistance profile