Perianal Plaques of Cytomegalovirus in a Patient with Central Nervous System Lymphoma

Cutaneous manifestations of cytomegalovirus (CMV) in patients without human immunodeficiency virus remain rare. Perianal CMV may be observed due to periodic fecal shedding but may be confused for other pathogens, and definitive diagnosis requires histopathologic examination. An instructive case is described, and the literature reviewed

Diagnosis and Interim Treatment Outcomes from the First Cohort of Multidrug-Resistant Tuberculosis Patients in Tanzania.

Kibong'oto National Tuberculosis Hospital (KNTH), Kilimanjaro, Tanzania. Characterize the diagnostic process and interim treatment outcomes from patients treated for multidrug-resistant tuberculosis (MDR-TB) in Tanzania. A retrospective cohort study was performed among all patients treated at KNTH for pulmonary MDR-TB between November 2009 and September 2011. Sixty-one culture-positive MDR-TB patients initiated therapy, 60 (98%) with a prior history of TB treatment. Forty-one (67%) were male and 9 (14%) were HIV infected with a mean CD4 count of 424 (±106) cells/µl. The median time from specimen collection to MDR-TB diagnosis and from diagnosis to initiation of MDR-TB treatment was 138 days (IQR 101-159) and 131 days (IQR 32-233), respectively. Following treatment initiation four (7%) patients died (all HIV negative), 3 (5%) defaulted, and the remaining 54 (89%) completed the intensive phase. Most adverse drug reactions were mild to moderate and did not require discontinuation of treatment. Median time to culture conversion was 2 months (IQR 1-3) and did not vary by HIV status. In 28 isolates available for additional second-line drug susceptibility testing, fluoroquinolone, aminoglycoside and para-aminosalicylic acid resistance was rare yet ethionamide resistance was present in 9 (32%). The majority of MDR-TB patients from this cohort had survived a prolonged referral process, had multiple episodes of prior TB treatment, but did not have advanced AIDS and converted to culture negative early while completing an intensive inpatient regimen without serious adverse event. Further study is required to determine the clinical impact of second-line drug susceptibility testing and the feasibility of alternatives to prolonged hospitalization

A mobile microvolume UV/visible light spectrophotometer for the measurement of levofloxacin in saliva

INTRODUCTION: Therapeutic drug monitoring (TDM) for personalized dosing of fluoroquinolones has been recommended to optimize efficacy and reduce acquired drug resistance in the treatment of MDR TB. Therefore, the aim of this study was to develop a simple, low-cost, robust assay for TDM using mobile UV/visible light (UV/VIS) spectrophotometry to quantify levofloxacin in human saliva at the point of care for TB endemic settings. METHODS: All experiments were performed on a mobile UV/VIS spectrophotometer. The levofloxacin concentration was quantified by using the amplitude of the second-order spectrum between 300 and 400 nm of seven calibrators. The concentration of spiked samples was calculated from the spectrum amplitude using linear regression. The method was validated for selectivity, specificity, linearity, accuracy and precision. Drugs frequently co-administered were tested for interference. RESULTS: The calibration curve was linear over a range of 2.5-50.0 mg/L for levofloxacin, with a correlation coefficient of 0.997. Calculated accuracy ranged from -5.2% to 2.4%. Overall precision ranged from 2.1% to 16.1%. Application of the Savitsky-Golay method reduced the effect of interferents on the quantitation of levofloxacin. Although rifampicin and pyrazinamide showed analytical interference at the lower limit of quantitation of levofloxacin concentrations, this interference had no implication on decisions regarding the levofloxacin dose. CONCLUSIONS: A simple UV/VIS spectrophotometric method to quantify levofloxacin in saliva using a mobile nanophotometer has been validated. This method can be evaluated in programmatic settings to identify patients with low levofloxacin drug exposure to trigger personalized dose adjustment

Prevalence of methicillin-resistant Staphylococcus aureus nasal carriage among hospitalised patients with tuberculosis in rural KwaZulu-Natal

Background. There is little information regarding the presence and characteristics of methicillin-resistant Staphylococcus aureus (MRSA), an important nosocomial pathogen, in rural African hospitals. Objectives. To determine the prevalence of MRSA colonisation in patients admitted to a rural hospital with tuberculosis (TB) in an endemic HIV area and to describe transmission dynamics and resistance patterns among MRSA isolates. Methods. A prospective prevalence survey in the adult TB wards of the Church of Scotland Hospital, a provincial government district hospital in Tugela Ferry, KwaZulu-Natal. Patients were eligible if over the age of 15 and admitted to the TB wards between 15 November and 15 December 2008. Nasal swabs were cultured within 24 hours of admission and repeated at hospital-day 14 or upon discharge. Susceptibility testing was performed with standard disk diffusion. Demographic and clinical information was extracted from medical charts. Results. Of 52 patients with an admission nasal swab, 11 (21%) were positive for MRSA. An additional 4 (10%) of patients with negative admission swabs were positive for MRSA on repeat testing. MRSA carriage on admission was more common among patients with previous hospitalisation, among HIV-infected patients was significantly assciated with lower CD4 counts (p=0.03). All MRSA isolates were resistant to cotrimoxazole, and 74% were resistant to ≥5 classes of antibiotics; all retained susceptibility to vancomycin. Conclusions. A high prevalence of multidrug-resistant MRSA nasal carriage was found. Studies are needed to validate nosocomial acquisition and to evaluate the impact of MRSA on morbidity and mortality among TB patients in similar settings

Individualizing management of extensively drug-resistant tuberculosis:diagnostics, treatment, and biomarkers

Contains fulltext : 170267.pdf (Publisher’s version ) (Open Access)INTRODUCTION: Success rates for treatment of extensively drug resistant tuberculosis (XDR-TB) are low due to limited treatment options, delayed diagnosis and inadequate health care infrastructure. Areas covered: This review analyses existing programmes of prevention, diagnosis and treatment of XDR-TB. Improved diagnostic procedures and rapid molecular tests help to select appropriate drugs and dosages. Drugs dosages can be further tailored to the specific conditions of the patient based on quantitative susceptibility testing of the M. tuberculosis isolate and use of therapeutic drug monitoring. Pharmacovigilance is important for preserving activity of the novel drugs bedaquiline and delamanid. Furthermore, biomarkers of treatment response must be developed and validated to guide therapeutic decisions. Expert commentary: Given the currently poor treatment outcomes and the association of XDR-TB with HIV in endemic regions, a more patient oriented approach regarding diagnostics, drug selection and tailoring and treatment evaluation will improve treatment outcome. The different areas of expertise should be covered by a multidisciplinary team and may involve the transition of patients from hospitalized to home or community-based treatment

Comparison of Overnight Pooled and Standard Sputum Collection Method for Patients with Suspected Pulmonary Tuberculosis in Northern Tanzania.

In Tanzania sputum culture for tuberculosis (TB) is resource intensive and available only at zonal facilities. In this study overnight pooled sputum collection technique was compared with standard spot morning collection among pulmonary TB suspects at Kibong'oto National TB Hospital in Tanzania. A spot sputum specimen performed at enrollment, an overnight pooled sputum, and single morning specimen were collected from 50 subjects and analyzed for quality, quantity, and time to detection in Bactec MGIT system. Forty-six (92%) subjects' overnight pooled specimens had a volume ≥5 mls compared to 37 (37%) for the combination of spot and single morning specimens (P < 0.001). Median time to detection was 96 hours (IQR 87-131) for the overnight pooled specimens compared to 110.5 hours (IQR is 137 right 137-180) for the combination of both spot and single morning specimens (P = 0.001). In our setting of limited TB culture capacity, we recommend a single pooled sputum to maximize yield and speed time to diagnosis

Therapeutic Drug Monitoring of Anti-infective Drugs:Implementation Strategies for 3 Different Scenarios

BACKGROUND: Therapeutic drug monitoring (TDM) supports personalized treatment. For successful implementation, TDM must have a turnaround time suited to the clinical needs of patients and their health care settings. Here, the authors share their views of how a TDM strategy can be tailored to specific settings and patient groups. METHODS: The authors selected distinct scenarios for TDM: high-risk, complex, and/or critically ill patient population; outpatients; and settings with limited laboratory resources. In addition to the TDM scenario approach, they explored potential issues with the legal framework governing dose escalation. RESULTS: The most important issues identified in the different scenarios are that critically ill patients require rapid turnaround time, outpatients require an easy sampling procedure for the sample matrix and sample collection times, settings with limited laboratory resources necessitate setting-specific analytic techniques, and all scenarios warrant a legal framework to capture the use of escalated dosages, ideally with the use of trackable dosing software. CONCLUSIONS: To benefit patients, TDM strategies need to be tailored to the intended population. Strategies can be adapted for rapid turnaround time for critically ill patients, convenient sampling for outpatients, and feasibility for those in settings with limited laboratory resources

Multiple Pathogens Contribute to Human Immunodeficiency Virus-Related Sepsis in Addition to Mycobacterium tuberculosis: A Prospective Cohort in Tanzania

This research article was published in the Int J Mycobacteriol. 2022 Jul-Sep; 11(3)Background: Mortality from tuberculosis (TB) sepsis is common among patients living with human immunodeficiency virus (PLHIV). We aimed to detect M. tuberculosis (MTB) and additional sepsis etiologies, and mortality determinants in PLHIV. Methods: This prospective cohort study consented and followed-up PLHIV for 28 days in northern Tanzania. From May through December 2021, patients provided urine and sputum for TB testing in lateral-flow lipoarabinomannan (LF-LAM) and Xpert® MTB/RIF. Bacterial blood culture, cryptococcal antigen, malaria rapid diagnostic, C-reactive-protein (CRP), and international normalized ratio (INR) tests were also performed. Sepsis severity was clinically measured by Karnofsky and modified early warning signs (MEWS) scores. Anti-TB, broad-spectrum antibiotics, and antimalarial and antifungal agents were prescribed in accordance with Tanzania treatment guideline. An independent t-test and Chi-square or Fisher’s exact tests compared means and proportions, respectively. P < 0.05 was statistically significant. Results: Among 98 patients, 59 (60.2%) were female. Their mean (standard deviation) age was 44 (12.9) years. TB detection increased from 24 (24.5%) by Xpert® MTB/RIF to 36 (36.7%) when LF-LAM was added. In total, 23 (23.5%) patients had other than TB etiologies of sepsis, including Staphylococcus aureus, Streptococcus pneumoniae, Cryptococcus spp., and Plasmodium spp. Twenty-four (94.4%) of 36 patients with TB had higher CRP (≥10 mg/l) compared to 25 (40.3%) non-TB patients (P 6 (n = 8), and malnutrition (n = 9). Conclusions: MTB and other microbes contributed to sepsis in PLHIV. Adding non-TB tests informed clinical decisions. Mortality was predicted by conventional sepsis and severity scoring, malnutrition, and elevated INR

Integrating pharmacokinetics and pharmacodynamics in operational research to end tuberculosis

Tuberculosis (TB) elimination requires innovative approaches. The new Global Tuberculosis Network (GTN) aims to conduct research on key unmet therapeutic and diagnostic needs in the field of TB elimination using multidisciplinary, multisectorial approaches. The TB Pharmacology section within the new GTN aims to detect and study the current knowledge gaps, test potential solutions using human pharmacokinetics informed through preclinical infection systems, and return those findings to the bedside. Moreover, this approach would allow prospective identification and validation of optimal shorter therapeutic durations with new regimens. Optimized treatment using available and repurposed drugs may have an increased impact when prioritizing a personcentered approach and acknowledge the importance of age, gender, comorbidities, and both social and programmatic environments. In this viewpoint article, we present an in-depth discussion on how TB pharmacology and the related strategies will contribute to TB elimination