Francis Kalemeera

Antimicrobial sensitivity patterns of cerebrospinal fluid (CSF) isolates in Namibia: implications for empirical antibiotic treatment of meningitis.

ObjectiveBacterial meningitis is a medical emergency associated with high mortality rates. Cerebrospinal fluid (CSF) culture is the “gold standard” for diagnosis of meningitis and it is important to establish the susceptibility of the causative microorganism to rationalize treatment. The Namibia Standard Treatment Guidelines (STGs) recommends initiation of empirical antibiotic treatment in patients with signs and symptoms of meningitis after taking a CSF sample for culture and sensitivity. The objective of this study was to assess the antimicrobial sensitivity patterns of microorganisms isolated from CSF to antibiotics commonly used in the empirical treatment of suspected bacterial meningitis in Namibia.MethodsThis was a cross-sectional descriptive study of routinely collected antibiotic susceptibility data from the Namibia Institute of Pathology (NIP) database. Results of CSF culture and sensitivity from January 1, 2009 to May 31, 2012, from 33 state hospitals throughout Namibia were analysed.ResultsThe most common pathogens isolated were Streptococcus species, Neisseria meningitidis, Haemophilus influenzae, Staphylococcus, and Escherichia coli. The common isolates from CSF showed high resistance (34.3% –73.5%) to penicillin. Over one third (34.3%) of Streptococcus were resistance to penicillin which was higher than 24.8% resistance in the United States. Meningococci were susceptible to several antimicrobial agents including penicillin. The sensitivity to cephalosporins remained high for Streptococcus, Neisseria, E. coli and Haemophilus. The highest percentage of resistance to cephalosporins was seen among ESBL K. pneumoniae (n = 7, 71%–100%), other Klebsiella species (n = 7, 28%–80%), and Staphylococcus (n = 36, 25%–40%).ConclusionsThe common organisms isolated from CSF were Streptococcus Pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Staphylococcus, and E. coli. All common organisms isolated from CSF showed high sensitivity to cephalosporins used in the empirical treatment of meningitis. The resistance of the common isolates to penicillin is high. Most ESBL K. pneumoniae were isolated from CSF samples drawn from neonates and were found to be resistant to the antibiotics recommended in the Namibia STGs. Based on the above findings, it is recommended to use a combination of aminoglycoside and third-generation cephalosporin to treat non–ESBL Klebsiella isolates. Carbapenems (e.g., meropenem) and piperacillin/tazobactam should be considered for treating severely ill patients with suspected ESBL Klebsiella infection. Namibia should have a national antimicrobial resistance surveillance system for early detection of antibiotics that may no longer be effective in treating meningitis and other life-threatening infections due to resistance.

Outcome of the first Medicines Utilization Research in Africa group meeting to promote sustainable and rational medicine use in Africa

The first Medicines Utilization Research in Africa group workshop and symposium brought researchers together from across Africa to improve their knowledge on drug utilization methodologies as well as exchange ideas. As a result, progress was made on drug utilization research and formulating future strategies to enhance the rational use of medicines in Africa. Anti-infectives were the principal theme for the 1-day symposium following the workshops. This included presentations on the inappropriate use of antibiotics as well as ways to address this. Concerns with adverse drug reactions and adherence to anti-retroviral medicines were also discussed, with poor adherence remaining a challenge. There were also concerns with the underutilization of generics. These discussions resulted in a number of agreed activities before the next conference in 2016.

Compliance to guidelines for the prescribing of antibiotics in acute infections at Namibia’s national referral hospital: a pilot study and the implications

ABSTRACT Background: Sub-optimal antibiotic prescribing remains a public health concern in Namibia. The objective was to determine the level and predictors of compliance to guidelines in the prescribing of antibiotics in acute infections at a national referral hospital in Namibia to improve future prescribing. Methods: An analytical cross-sectional survey design. The clinical records of patients receiving care were reviewed. Prescribing practices were assessed using a self- administered questionnaire with reference to Namibia Standard Treatment Guidelines (NSTG). Results: The majority of prescriptions (62%) complied with the NSTGs; however, lower than national targets (95%). Most prescriptions were empiric and prescribers typically made reference to the NSTG (58%). Diagnosed infections were principally respiratory infections (58%) and penicillins were the most used antibiotics. Good concurrence between signs and symptoms with the diagnosis indicated on the prescription - OR=5.2 (95% CI: 1.4, 19.2), a diagnosis of upper respiratory tract (p=0.001), oral-dental OR=0.1(95% CI: 0.03,0.3) and urogenital infections OR=0.3(95% CI: 0.1,0.95) and the prescribing of penicillins (p=0.001) or combination antibiotics and amphenicols were independent predictors of compliance to the NSTGs. The main behaviours associated with antibiotic prescribing were patient influences, clinical state, and access to guidelines. Conclusions: Compliance with NSTGs is suboptimal. Prescribing of combination antibiotics, penicillins and diagnosis of oral dental, genitourinary and ear, nose and throat infections were important predictors for NSTG compliance. There is a need to implement antibiotic indicators and stewardship programmes, and ensure access to NSTGs, to improve future antibiotic prescribing in Namibia.

Effect of changing from first- to second- line antiretroviral therapy on renal function: a retrospective study based on data from a single health facility in Namibia

ABSTRACT Background: Tenofovir disoproxil fumarate (TDF) and lopinavir/ritonavir (LPV/r) can cause renal impairment with this combination co-administered during second-line combination antiretroviral therapy (cART) potentially associated with greater risk of nephrotoxicity. As a result, the aim of this study is to assess effects of second-line cART on renal function. Methods: Retrospective longitudinal study in patients receiving cART. Results: 71 patients received TDF, zidovudine or stavudine, each combined with 3TC/NVP or 3TC/EFV. Before second-line cART, 46.5% had abnormal kidney function. First-line cART had no relationship with calculated creatinine clearance (CrCl). During second-line cART, more males than females had abnormal renal function and more females experienced increases in CrCl. Calculated CrCl during second-line cART related strongly with CrCl during first-line cART. Time spent on cART weak had a week relationship with CrCl. Conclusion: Patients on first-line cART for several years without renal impairment may experience new onset impairment during second line cART. Patients with pre-existing renal impairment just before switching to second-line cART may experience a further decline.

Outcome of the second Medicines Utilisation Research in Africa Group meeting to promote sustainable and appropriate medicine use in Africa

ABSTRACT The second Medicines Utilization Research in Africa (MURIA) group workshop and symposium again brought researchers together from across Africa to improve their knowledge of drug utilization (DU) methodologies and exchange ideas to further progress DU research in Africa. This built on extensive activities from the first conference including workshops and multiple publications. Anti-infectives were again the principal theme for the 2016 symposium following the workshops. This included presentations regarding strategies to improve antibiotic utilization among African countries, such as point-prevalence studies, as well as potential ways to reduce self-purchasing of antibiotics. There were also presentations on antiretrovirals including renal function and the impact of policy changes. Concerns with adherence in chronic treatments as well as drug-drug interactions and their implications were also discussed. The deliberations resulted in a number of agreed activities including joint publications before the next MURIA conference in Namibia in 2017.

Liver enzyme elevations in a cohort of HIV/AIDS patients on first-line antiretroviral therapy in Namibia: Findings and implications

Highlights • All antiretroviral therapies (ARTs) are potentially toxic to the liver. The rising incidence of ART induced adverse events has led to guideline revision.• The rising incidence of ART induced adverse events has led to guideline revision. Limited studies to date evaluating ART induced liver injury in these countries. This need to be addressed to guide future clinical practice.• Majority of patients developed significant ALT elevation within 3 months of ART initiation. No significant difference between mean ALT levels at baseline and month 6.• Patients with high risk of hepatocellular damage, female sex, and > grade 2 ALT elevations, and patients who test positive for HBV/HCV, should be monitored for at least 6 months after initiation of NVP and EFV based ART. Abstract Introduction All antiretroviral therapies (ARTs) are potentially toxic to the liver. In sub-Saharan Africa, the rising incidence of ART induced adverse events has complicated treatment leading to recent revisions of Namibian ART guidelines. Unfortunately there have been limited studies to date evaluating ART induced liver injury in Namibia to guide further revisions if needed. Objective Determine the current patterns and grades of ALT elevation in Namibia’s HIV/AIDS. Methods Retrospective cohort analysis. Patterns of alanine amino transferase (ALT) liver enzyme elevation were determined in a cohort of ART naïve HIV patients on firstline ART regimen in a referral hospital in Namibia over a 1 year treatment period. Patterns of ALT changes at baseline, 3 months and 6 months were analyzed using ANOVA and Bonferroni test for pairwise comparisons. Results Of 79 eligible patients, 72 developed significant ALT elevation within 3 months of ART initiation (F (3, 76) = 6.4, p = 0.002, η2 = 0.193). Four 4 (5.6%) and 1 (1.38%) patient respectively developed grade 2 and grade 3 ALT elevation by month 3. There was no significant difference between mean ALT levels at baseline and month 6. A CD4 count of <350 cells/mm3; female gender and age over 40 years were the main factors associated with moderate or severe ALT elevation. Conclusions First line ART commonly induces mild self-limiting liver enzyme elevation in Namibian HIV patients especially in the first 3 months. Consequently, there is a need to monitor ALT levels for at least 3 months after initiation mainly in high risk patients to reduce side-effect concerns. This is already happening.

Tenofovir substitution in Namibia based on an analysis of the antiretroviral dispensing database

ObjectivesIn the management of HIV infection, tenofovir is preferred to its predecessors – zidovudine and stavudine – in the antiretroviral therapy (ART) nucleoside backbone. Tenofovir’s (TDF) preference is based on its safety profile. Nevertheless, TDF causes adverse reactions, some of which warrant its substitution for patients. The rate of TDF-substitution is suggestive of the rate of occurrence of TDF-related adverse reactions. However, the rate of substitution of TDF with another nucleoside reverse transcriptase inhibitor (NRTI) in Namibia was unknown. The objective of this review was to measure the rate of TDF’s substitution for the period of January 1, 2008 to November 30, 2011, and to compare the gender difference in the rates of TDF’s substitution.MethodsWe accessed antiretroviral medicine dispensing records from the national antiretroviral dispensing database (NDB). We selected patients who were started on a TDF-containing conventional ART regimen – 2NRTI+1NNRT. We used the initial and current ART regimens to identify records of TDF’s substitution with another NRTI.ResultsA total of 84,741 patients were initiated on ART (Jan-1-2008 to Nov-30-2011). A total of 52,612 patient-records were excluded from the analysis because they did not meet the criteria for inclusion. Of the 32,129 included records, 59.4% (n=19 096) and 40.6% (n=13 033) were for female and male patients, respectively. Of these, 1.2% (n=380) of the patients had their TDF substituted with another NRTI. Of the females and males, respectively, 1.1% (95% CI: 0.9-1.3; n=210) and 1.3% (95% CI: 1.1-1.5; n=170) had TDF substituted with another NRTI. No gender difference was observed (p-value = 0.11).ConclusionThe percentage of patients for whom TDF was substituted with another NRTI, possibly due to TDF-related adverse reactions, was within the current published limits. However, 1.2% is likely not a true representation of the percentage of patients who experience adverse events because some patients could have been maintained on TDF even in the presence of adverse events. Further investigation is required to determine the clinical reasons for TDF’s withdrawal.

Implementing clinical pharmacy within undergraduate teaching in Namibia

Clinical pharmacy is currently not practised in Namibia. To introduce the concept and skills pertinent to this area of practice, pharmacy undergraduates at Namibia’s new School of Pharmacy are introduced to clinical pharmacy from their second year, and progress from theory to practical application on the wards. This approach has led to students having a greater understanding of clinical pharmacy and how it can be applied in practice. Introducing clinical pharmacy progressively at an undergraduate level may help to stimulate interest in the speciality for future career progression.

The Potential Effect of Using the Cockcroft-Gault Method on Tenofovir-Associated Renal Impairment Reports and on Clinical Decisions Regarding Tenofovir Use in Individual Patients: Implications for the Future

Introduction: In Namibia, the Cockcroft-Gault (C-G) method is recommended for monitoring renal function in HIV patients receiving Tenofovir Disoproxil Fumarate (TDF)-containing Combination Antiretroviral Therapy (cART). However, there are concerns with the potential over-reporting of TDF-associated renal impairment. Methods: Retrospective study comparing the renal function of patients receiving 2nd line cART with either C-G or Chronic Kidney Disease-Epidemiology (CKD-EPI) methods. Results: 71 patients were included. The majority (62%) received TDF-containing 1st line ART. All received 2ndline cART containing TDF/Lamivudine (3TC)/Zidovudine (AZT) and LPV/r. Before switching to 2nd-line cART, 40.8% and 8.5% had abnormal eGFR according to C-G and CKD-EPI methods respectively. During 2nd-line cART, 47.9% and 7% of patients had abnormal eGFR by C-G and CKD-EPI methods, respectively, and 4.1% and 2.8% respectively experienced a decline in eGFR. There was a significant lack of agreement between the two methods. Conclusion: The C-G method has the potential to report more cases of TDF-associated renal impairment. Consequently, national guidelines in Namibia and other pertinent countries should be reviewed if this is the recommended method for monitoring renal function.

Evidence on the cost-effectiveness of lifelong antiretroviral therapy for prevention of mother-to-child transmission of HIV: implications for resource-limited countries in sub-Saharan Africa

ABSTRACT Introduction: The 2016 World Health Organization (WHO) consolidated guideline recommends lifelong antiretroviral therapy (ART) for all HIV-infected pregnant and breastfeeding women for preventing mother-to-child HIV transmission (PMTCT). Ambiguity remains about the cost-effectiveness of this strategy in resource-limited developing countries. Areas covered: We reviewed model-based studies on the cost-effectiveness of lifelong ART (formerly Option B+) relative to previous WHO guidelines for PMTCT. Our search using PubMed, Medline and Google Scholar for articles on Option B+ resulted in the final inclusion of seven studies published between 2012 and 2016. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist was used to assess the quality of reporting. Outcomes of interest, which included infant infections averted, maternal quality and length of life, and the Incremental Cost Effectiveness Ratio (ICER), were used in comparing cost-effectiveness. Expert commentary: Despite most model-based studies favouring lifelong ART (Option B+) in terms of its cost-effectiveness in comparison to Options A and B, inclusiveness of the evidence remains weak for generalization. This is largely because setting specificity for providing lifelong ART to all pregnant and breastfeeding women may differ significantly in each setting. Consequently, future cost-effectiveness studies should be robust, setting-specific, and endeavor to assess the willingness and ability to pay of each setting.