Intravenous ketamine for severe alcohol use disorder at Moi Teaching & Referral Hospital, Kenya: a case report.

BACKGROUND: Alcohol use disorder is prevalent globally and in Kenya, and is associated with significant health and socio-economic consequences. Despite this, available pharmacological treatment options are limited. Recent evidence indicates that intravenous (IV) ketamine can be beneficial for the treatment of alcohol use disorder, but is yet to be approved for this indication. Further, little has been done to describe the use of IV ketamine for alcohol use disorder in Africa. The goal of this paper, is to: 1) describe the steps we took to obtain approval and prepare for off-label use of IV ketamine for patients with alcohol use disorder at the second largest hospital in Kenya, and 2) describe the presentation and outcomes of the first patient who received IV ketamine for severe alcohol use disorder at the hospital. CASE PRESENTATION: In preparing for the off-label use of ketamine for alcohol use disorder, we brought together a multi-disciplinary team of clinicians including psychiatrists, pharmacists, ethicists, anesthetists, and members of the drug and therapeutics committee, to spearhead the process. The team developed a protocol for administering IV ketamine for alcohol use disorder that took into account ethical and safety issues. The national drug regulatory authority, the Pharmacy and Poison's Board, reviewed and approved the protocol. Our first patient was a 39-year-old African male with severe alcohol use disorder and comorbid tobacco use disorder and bipolar disorder. The patient had attended in-patient treatment for alcohol use disorder six times and each time had relapsed between one to four months after discharge. On two occasions, the patient had relapsed while on optimal doses of oral and implant naltrexone. The patient received IV ketamine infusion at a dose of 0.71 mg/kg. The patient relapsed within one week of receiving IV ketamine while on naltrexone, mood stabilizers, and nicotine replacement therapy. DISCUSSION & CONCLUSIONS: This case report describes for the first time the use of IV ketamine for alcohol use disorder in Africa. Findings will be useful in informing future research and in guiding other clinicians interested in administering IV ketamine for patients with alcohol use disorder.

Point-prevalence survey of antibiotic use at three public referral hospitals in Kenya.

Antimicrobial stewardship encourages appropriate antibiotic use, the specific activities of which will vary by institutional context. We investigated regional variation in antibiotic use by surveying three regional public hospitals in Kenya. Hospital-level data for antimicrobial stewardship activities, infection prevention and control, and laboratory diagnostic capacities were collected from hospital administrators, heads of infection prevention and control units, and laboratory directors, respectively. Patient-level antibiotic use data were abstracted from medical records using a modified World Health Organization point-prevalence survey form. Altogether, 1,071 consenting patients were surveyed at Kenyatta National Hospital (KNH, n = 579), Coast Provincial General Hospital (CPGH, n = 229) and Moi Teaching and Referral Hospital (MTRH, n = 263). The majority (67%, 722/1071) were ≥18 years and 53% (563/1071) were female. Forty-six percent (46%, 489/1071) were receiving at least one antibiotic. Antibiotic use was higher among children <5 years (70%, 150/224) than among other age groups (40%, 339/847; P < 0.001). Critical care (82%, 14/17 patients) and pediatric wards (59%, 155/265) had the highest proportion of antibiotic users. Amoxicillin/clavulanate was the most frequently used antibiotic at KNH (17%, 64/383 antibiotic doses), and ceftriaxone was most used at CPGH (29%, 55/189) and MTRH (31%, 57/184). Forty-three percent (326/756) of all antibiotic prescriptions had at least one missed dose recorded. Forty-six percent (204/489) of patients on antibiotics had a specific infectious disease diagnosis, of which 18% (37/204) had soft-tissue infections, 17% (35/204) had clinical sepsis, 15% (31/204) had pneumonia, 13% (27/204) had central nervous system infections and 10% (20/204) had obstetric or gynecological infections. Of these, 27% (56/204) had bacterial culture tests ordered, with culture results available for 68% (38/56) of tests. Missed antibiotic doses, low use of specimen cultures to guide therapy, high rates of antibiotic use, particularly in the pediatric and surgical population, and preference for broad-spectrum antibiotics suggest antibiotic use in these tertiary care hospitals is not optimal. Antimicrobial stewardship programs, policies, and guidelines should be tailored to address these areas.

Opportunities for Improving Antimicrobial Stewardship: Findings From a Prospective, Multi-Center Study in Three Low- or Middle-Income Countries.

Background: To develop effective antimicrobial stewardship programs (ASPs) for low- and middle-income countries (LMICs), it is important to identify key targets for improving antimicrobial use. We sought to systematically describe the prevalence and patterns of antimicrobial use in three LMIC hospitals. Methods: Consecutive patients admitted to the adult medical wards in three tertiary care hospitals in Tanzania, Kenya, and Sri Lanka were enrolled in 2018-2019. The medical record was reviewed for clinical information including type and duration of antimicrobials prescribed, indications for antimicrobial use, and microbiologic testing ordered. Results: A total of 3,149 patients were enrolled during the study period: 1,103 from Tanzania, 750 from Kenya, and 1,296 from Sri Lanka. The majority of patients were male (1,783, 56.6% overall) with a median age of 55 years (IQR 38-68). Of enrolled patients, 1,573 (50.0%) received antimicrobials during their hospital stay: 35.4% in Tanzania, 56.5% in Kenya, and 58.6% in Sri Lanka. At each site, the most common indication for antimicrobial use was lower respiratory tract infection (LRTI; 40.2%). However, 61.0% received antimicrobials for LRTI in the absence of LRTI signs on chest radiography. Among patients receiving antimicrobials, tools to guide antimicrobial use were under-utilized: microbiologic cultures in 12.0% and microbiology consultation in 6.5%. Conclusion: Antimicrobials were used in a substantial proportion of patients at tertiary care hospitals across three LMIC sites. Future ASP efforts should include improving LRTI diagnosis and treatment, developing antibiograms to direct empiric antimicrobial use, and increasing use of microbiologic tests.

Barriers to implementing antimicrobial stewardship programs in three low- and middle-income country tertiary care settings: findings from a multi-site qualitative study.

BACKGROUND: Antimicrobial resistance has been named as one of the top ten threats to public health in the world. Hospital-based antimicrobial stewardship programs (ASPs) can help reduce antimicrobial resistance. The purpose of this study was to determine perceived barriers to the development and implementation of ASPs in tertiary care centers in three low- and middle-income countries (LMICs). METHODS: Interviews were conducted with 45 physicians at tertiary care hospitals in Sri Lanka (n = 22), Kenya (12), and Tanzania (11). Interviews assessed knowledge of antimicrobial resistance and ASPs, current antimicrobial prescribing practices, access to diagnostics that inform antimicrobial use, receptiveness to ASPs, and perceived barriers to implementing ASPs. Two independent reviewers coded the interviews using principles of applied thematic analysis, and comparisons of themes were made across the three sites. RESULTS: Barriers to improving antimicrobial prescribing included prohibitively expensive antimicrobials, limited antimicrobial availability, resistance to changing current practices regarding antimicrobial prescribing, and limited diagnostic capabilities. The most frequent of these barriers in all three locations was limited drug availability. Many physicians in all three sites had not heard of ASPs before the interviews. Improved education was a suggested component of ASPs at all three sites. The creation of guidelines was also recommended, without prompting, by interviewees at all three sites. Although most participants felt microbiological results were helpful in tailoring antibiotic courses, some expressed distrust of laboratory culture results. Biomarkers like erythrocyte sedimentation rate and c-reactive protein were not felt to be specific enough to guide antimicrobial therapy. Despite limited or no prior knowledge of ASPs, most interviewees were receptive to implementing protocols that would include documentation and consultation with ASPs regarding antimicrobial prescribing. CONCLUSIONS: Our study highlighted several important barriers to implementing ASPs that were shared between three tertiary care centers in LMICs. Improving drug availability, enhancing availability of and trust in microbiologic data, creating local guidelines, and providing education to physicians regarding antimicrobial prescribing are important steps that could be taken by ASPs in these facilities.

Neurocognitive Function at the First-Line Failure and on the Second-Line Antiretroviral Therapy in Africa: Analyses From the EARNEST Trial.

OBJECTIVE: To assess neurocognitive function at the first-line antiretroviral therapy failure and change on the second-line therapy. DESIGN: Randomized controlled trial was conducted in 5 sub-Saharan African countries. METHODS: Patients failing the first-line therapy according to WHO criteria after >12 months on non-nucleoside reverse transcriptase inhibitors-based regimens were randomized to the second-line therapy (open-label) with lopinavir/ritonavir (400 mg/100 mg twice daily) plus either 2-3 clinician-selected nucleoside reverse transcriptase inhibitors, raltegravir, or as monotherapy after 12-week induction with raltegravir. Neurocognitive function was tested at baseline, weeks 48 and 96 using color trails tests 1 and 2, and the Grooved Pegboard test. Test results were converted to an average of the 3 individual test z-scores. RESULTS: A total of 1036 patients (90% of those >18 years enrolled at 13 evaluable sites) had valid baseline tests (58% women, median: 38 years, viral load: 65,000 copies per milliliter, CD4 count: 73 cells per cubic millimeter). Mean (SD) baseline z-score was -2.96 (1.74); lower baseline z-scores were independently associated with older age, lower body weight, higher viral load, lower hemoglobin, less education, fewer weekly working hours, previous central nervous system disease, and taking fluconazole (P < 0.05 in multivariable model). Z-score was increased by mean (SE) of +1.23 (0.04) after 96 weeks on the second-line therapy (P < 0.001; n = 915 evaluable), with no evidence of difference between the treatment arms (P = 0.35). CONCLUSIONS: Patients in sub-Saharan Africa failing the first-line therapy had low neurocognitive function test scores, but performance improved on the second-line therapy. Regimens with more central nervous system-penetrating drugs did not enhance neurocognitive recovery indicating this need not be a primary consideration in choosing a second-line regimen.

Factors Associated with Late Engagement to HIV Care in Western Kenya: A Cross-Sectional Study.

BACKGROUND: Late presentation of patients contributes significantly to the high mortality reported in HIV -care and treatment programs in sub-Saharan Africa. METHODS: A cross-sectional study was conducted to assess factors associated with late engagement to HIV care at the Academic Model Providing Access to Healthcare in western Kenya. Late engagement was defined as baseline CD4 ≤100 cells/mm3. RESULTS: Of the 10 533 participants included in the analysis, 67% were female and mean age was 36.7 years. Overall, 23% of the participants presented late. Factors associated with late engagement included male gender (adjusted odds ratio [AOR]: 1.54, 95% confidence interval [CI]: 1.35-1.75), older age (AOR: 1.62, 95% CI: 1.02-2.56), and longer travel time to clinic (AOR: 1.18, 95% CI: 1.04-1.34). CONCLUSION: Nearly one-quarter of HIV-infected patients in our setting present with advanced immune suppression at initial encounter. Being male, older age, and living further away from clinic are associated with late engagement to care.

Sickle cell disease and HIV: a case highlighting management challenges for children in a resource-limited setting.

Sickle cell disease (SCD) is a genetic disorder resulting from a mutation in the hemoglobin (Hb) gene. Sickle cell disease results in chronic anemia and a variety of acute and chronic complications that can lead to early mortality. A child with both SCD and HIV presents a management challenge, particularly in a resource-limited setting. In this case report, we describe the case of an 18-month-old Kenyan girl with SCD and HIV who developed a severe hypersensitivity reaction to first-line antiretroviral therapy (ART). Selecting an appropriate drug substitute for a child with SCD and HIV presents a management dilemma when the available options have problematic side effect profiles or are inaccessible or inappropriate according to national guidelines. The challenges in choosing an appropriate ART regimen for a child with SCD and HIV highlight the lack of data and scarcity of treatment options for pediatric patients.

Human immunodeficiency virus and leprosy coinfection: challenges in resource-limited setups.

Mycobacteria leprae(leprosy) and HIV coinfection are rare in Kenya. This is likely related to the low prevalence (1 per 10,000 of population) of leprosy. Because leprosy is no longer a public health challenge there is generally a low index of suspicion amongst clinicians for its diagnosis. Management of a HIV-1-leprosy-coinfected individual in a resource-constrained setting is challenging. Some of these challenges include difficulties in establishing a diagnosis of leprosy; the high pill burden of cotreatment with both antileprosy and antiretroviral drugs (ARVs); medications' side effects; drug interactions; scarcity of drug choices for both diseases. This challenge is more profound when managing a patient who requires second-line antiretroviral therapy (ART). We present an adult male patient coinfected with HIV and leprosy, who failed first-line antiretroviral therapy (ART) and required second-line treatment. Due to limited choices in antileprosy drugs available, the patient received monthly rifampicin and daily lopinavir-/ritonavir-based antileprosy and ART regimens, respectively. Six months into his cotreatment, he seemed to have adequate virological control. This case report highlights the challenges of managing such a patient.