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Clinical Microbiology and Infection :... Feb 2024Contacts of patients with multidrug-resistant tuberculosis (MDR-TB) are at risk of developing TB disease. Tuberculosis preventive treatment (TPT) is an intervention that... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Contacts of patients with multidrug-resistant tuberculosis (MDR-TB) are at risk of developing TB disease. Tuberculosis preventive treatment (TPT) is an intervention that can potentially reduce this risk.
OBJECTIVES
To evaluate the effectiveness and safety of TPT for contacts of patients with MDR-TB.
DATA SOURCES
EMBASE, PubMed, Web of Science, and the Cochrane Library were searched for eligible studies on 24 July 2023, without start date restrictions.
STUDY ELIGIBILITY CRITERIA
We included studies that compared TPT with no treatment in contacts of patients with MDR-TB and reported outcomes of progression to TB disease.
PARTICIPANTS
Contacts of patients with MDR-TB.
INTERVENTIONS
TPT.
ASSESSMENT OF RISK OF BIAS
A modified version of the Newcastle-Ottawa Scale was used.
METHODS OF DATA SYNTHESIS
Random-effects meta-analysis was utilized to calculate the relative risk for disease progression to TB in contacts of patients with MDR-TB who received TPT compared to those who did not. Additionally, completion, adverse effect, and discontinued rates were assessed.
RESULTS
Involving 1105 individuals from 11 studies, the pooled relative risk for disease progression in contacts receiving TPT versus those without treatment was 0.34 (95% CI: 0.16-0.72). Subgroup analysis indicated a lower pooled relative risk for regimens based on the drug-resistance profile of the index patients with TB compared to uniform treatment regimens (0.22 [95% CI: 0.06-0.84] vs. 0.49 [95% CI: 0.17-1.35]), although not statistically significant. The pooled completed rate was 83.8%, adverse effect rate was 22.9%, and discontinued rate was 6.5%. After excluding the levofloxacin and pyrazinamide regimen study, the completed rate increased to 88.0%, and adverse effects and discontinued rates decreased to 8.0% and 4.0%, respectively.
DISCUSSION
TPT reduces TB disease progression risk in contacts of patients with MDR-TB. Tailored TPT regimens based on drug-resistance profiles may offer additional benefits. Furthermore, efforts to improve completed rates and manage adverse effects are essential for optimizing effectiveness and safety.
Topics: Humans; Antitubercular Agents; Tuberculosis, Multidrug-Resistant; Pyrazinamide; Levofloxacin; Drug-Related Side Effects and Adverse Reactions; Disease Progression
PubMed: 37741621
DOI: 10.1016/j.cmi.2023.09.015 -
BMC Infectious Diseases Sep 2023Tuberculosis, along with HIV, is the leading cause of mortality and morbidity globally. Despite the fact that several primary studies have been conducted on the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tuberculosis, along with HIV, is the leading cause of mortality and morbidity globally. Despite the fact that several primary studies have been conducted on the incidence rate of tuberculosis in HIV-infected people in Sub-Saharan Africa, the regional-level tuberculosis incidence rate remains unknown. The objective of this study is to determine the tuberculosis incidence rate and its associated factors in HIV-infected people in Sub-Saharan Africa.
METHODS
A systematic review and meta-analysis were conducted by searching four databases for studies published in English between January 1, 2000, and November 25, 2022. The study was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method. To assess the quality of the studies, the Joanna Briggs Institute critical appraisal checklist was used. A random-effects model meta-analysis was used to determine the pooled incidence of tuberculosis using STATA version 15. The I heterogeneity test was used to assess heterogeneity. Subgroup and sensitivity analyses were performed. Funnel plots and Egger's regression tests were used to investigate publication bias. The pooled estimate predictors of tuberculosis incidence rate with a 95% confidence interval were also determined using the hazard ratio of each factor (HR).
RESULTS
Out of a total of 3339 studies, 43 were included in the analysis. The overall pooled incidence rate of tuberculosis in HIV-infected people was 3.49 per 100 person-years (95% CI: 2.88-4.17). In the subgroup analysis, the pooled incidence rate of tuberculosis in HIV-infected children was 3.42 per 100 person-years (95% CI: 1.78, 5.57), and it was 3.79 per 100 person-years (95% CI: 2.63, 5.15) in adults. A meta-analysis revealed that underweight (AHR = 1.79, 95% CI: 1.61-1.96), low CD4 count (AHR = 1.23, 95% CI: 1.13-1.35), male gender (AHR = 1.43, 95% CI: 1.22-1.64), advanced WHO clinical stages (AHR = 2.29, 95% CI: 1.34-3.23), anemia (AHR = 1.73, 95% CI: 1.34-2.13), bedridden or ambulatory (AHR = 1.87, 95%), lack of isoniazid preventive therapy (AHR = 3.32, 95% CI: 1.08-2.28), and lack of cotrimoxazole (AHR = 1.68, 95% CI: 1.08-2.28) were risk factors for tuberculosis incidence. HIV patients who received antiretroviral therapy had a 0.53 times higher risk of acquiring tuberculosis than HIV patients who did not receive antiretroviral therapy (AHR = 0.53; 95% CI: 0.3-0.77).
CONCLUSION
In this systematic review and meta-analysis study, the incidence rate of tuberculosis among HIV-positive people was higher than the WHO 2022 Africa regional estimated report. To reduce the incidence of tuberculosis among HIV patients, HIV patients should take isoniazid prevention therapy (IPT), cotrimoxazole prophylaxis, and antiretroviral therapy (ART) without interruption, as well as increase the frequency and diversity of their nutritional intake. Active tuberculosis screening should be increased among HIV-infected people.
Topics: Adult; Child; Male; Humans; Incidence; Isoniazid; HIV Infections; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis; Africa South of the Sahara
PubMed: 37723415
DOI: 10.1186/s12879-023-08533-0 -
Clinical Infectious Diseases : An... Jan 2024Native vertebral osteomyelitis (NVO) caused by Staphylococcus aureus is associated with high risk of treatment failure and increased morbidity. The role of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Native vertebral osteomyelitis (NVO) caused by Staphylococcus aureus is associated with high risk of treatment failure and increased morbidity. The role of rifampin-based therapy for the treatment of this condition is controversial. The goal of this systematic review and meta-analysis is to explore the efficacy and safety of rifampin-based therapy for the treatment of S. aureus NVO.
METHODS
We searched Cochrane, Embase, Medline, Scopus, and Web of Science databases for studies published up to May 2023, focusing on adults with NVO treated with or without rifampin-containing regimens. A random-effects model meta-analysis estimated relative risks and risk difference with 95% confidence intervals (CI).
RESULTS
Thirteen studies (2 randomized controlled trials and 11 comparative cohort studies), comprising 244 patients with S. aureus NVO who received rifampin and 435 who did not, were analyzed. Meta-analysis showed that rifampin-based regimens were associated with lower risk of clinical failure (risk difference, -14%; 95% CI, -19% to -8%; P < .001; I2 = 0%; relative risk, 0.58; 95% CI, .37-.92, P = .02, I2 = 21%). Only 1 study reported on adverse events. All studies had a high or uncertain risk of bias, and the certainty of evidence was rated as very low.
CONCLUSIONS
Adjunctive rifampin therapy might be associated with lower risk of S. aureus NVO treatment failure; however, the low certainty of evidence precludes drawing definitive conclusions that would alter clinical practice. A randomized trial is necessary to corroborate these findings.
Topics: Adult; Humans; Clinical Protocols; Osteomyelitis; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Anti-Bacterial Agents
PubMed: 37721158
DOI: 10.1093/cid/ciad560 -
Seminars in Arthritis and Rheumatism Dec 2023Invasive fungal infections (IFIs) are life-threatening opportunistic infections in patients with connective tissue disease CTD) that cause significant morbidity and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Invasive fungal infections (IFIs) are life-threatening opportunistic infections in patients with connective tissue disease CTD) that cause significant morbidity and mortality. We attempted to determine the potential risk factors associated with IFIs in CTD.
METHODS
We systematically searched PubMed, Embase, and the Cochrane Library databases for relevant articles published from the database inception to February 1, 2023.
RESULTS
Twenty-six studies were included in this systematic review and meta-analysis. Risk factors identified for IFIs were diabetes (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.00 to 2.64), pulmonary diseases (OR 3.43; 95% CI 2.49 to 4.73), interstitial lung disease (ILD; OR, 4.06; 95% CI, 2.22 to 7.41), renal disease (OR, 4.41; 95% CI, 1.84 to 10.59), glucocorticoid (GC) use (OR, 4.15; 95% CI, 2.74 to 6.28), especially moderate to high-dose GC, azathioprine (AZA) use (OR, 1.50; 95% CI, 1.12 to 2.01), calcineurin inhibitor (CNI) use (OR, 2.49; 95% CI, 1.59 to 3.91), mycophenolate mofetil (MMF) use (OR, 2.83; 95% CI, 1.59 to 5.03), cyclophosphamide (CYC) use (OR, 3.35; 95% CI, 2.47 to 4.54), biologics use (OR, 3.43; 95% CI, 2.36 to 4.98), and lymphopenia (OR, 4.26; 95% CI, 2.08 to 8.73). Hydroxychloroquine (HCQ) use reduced risk of IFIs (OR, 0.67; 95% CI, 0.54 to 0.84). Furthermore, 17 of the 26 studies only reported risk factors for Pneumocystis jiroveci pneumonia (PJP) in patients with CTD. Pulmonary disease; ILD; and the use of GC, CNIs, CYC, methotrexate (MTX), MMF and biologics, and lymphopenia increased the risk of PJP, whereas the use of HCQ reduced its risk.
CONCLUSION
Diabetes, pulmonary disease, ILD, renal disease, use of GC (especially at moderate to high dose) and immunosuppressive drugs, and lymphopenia were found to be associated with significant risk for IFIs (especially PJP) in patients with CTD. Furthermore, the use of HCQ may reduce the risk of IFIs in patients with CTD.
Topics: Humans; Connective Tissue Diseases; Cyclophosphamide; Lung Diseases, Interstitial; Mycophenolic Acid; Glucocorticoids; Risk Factors; Diabetes Mellitus; Lymphopenia; Biological Products; Invasive Fungal Infections
PubMed: 37633041
DOI: 10.1016/j.semarthrit.2023.152257 -
The Journal of Antimicrobial... Oct 2023To assess whether the addition of rifampicin to conventional treatment of Staphylococcus aureus bacteraemia (SAB) reduces bacteriological or clinical failure or death. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To assess whether the addition of rifampicin to conventional treatment of Staphylococcus aureus bacteraemia (SAB) reduces bacteriological or clinical failure or death.
DATA SOURCES
PubMed, Embase and Cochrane CENTRAL databases were searched from inception to 31 December 2022. Reference lists and PubMed citations of eligible studies were checked.
REVIEW METHODS
Two study authors independently identified randomized controlled trials (RCTs) involving adult participants with SAB, in which an intervention group received adjunctive rifampicin and the control group received usual care with or without a placebo. Dichotomous data (bacteriological and clinical failure and deaths) were analysed and pooled across studies using risk ratio (RR) with 95% confidence intervals (CI) using a Mantel-Haenszel random-effect model. The key variable of interest being whether rifampicin was used.
RESULTS
Six RCTs including 894 participants-of which 758 (85%) were from one trial-met the inclusion criteria. The addition of rifampicin to conventional treatment of SAB significantly reduced bacteriological failure by 59% (RR 0.41, 95% CI 0.21-0.81, I2 = 0%, number need to treat 27). However, it did not reduce clinical failure (RR 0.70, 95% CI 0.47-1.03, I2 = 0%) or deaths (RR 0.96, 95% CI 0.70-1.32, I2 = 0%). Further, it did not reduce the duration of bacteraemia, or the length of hospital stay. Adjunctive rifampicin reduced SAB recurrences (1% versus 4%, P = 0.01). Emergence of rifampicin resistance during treatment was uncommon (<1%).
CONCLUSION
Although adjunctive rifampicin reduced the risk of bacteriological failure and recurrences, we found no mortality benefit to support its use in SAB.
Topics: Adult; Humans; Rifampin; Randomized Controlled Trials as Topic; Staphylococcal Infections; Bacteremia; Staphylococcus aureus
PubMed: 37583062
DOI: 10.1093/jac/dkad214 -
Medicina (Kaunas, Lithuania) Jul 2023Limited data are available on the utilization of sodium thiosulfate (STS) treatment for calciphylaxis in peritoneal dialysis (PD) patients, while it is well-studied in... (Review)
Review
Limited data are available on the utilization of sodium thiosulfate (STS) treatment for calciphylaxis in peritoneal dialysis (PD) patients, while it is well-studied in hemodialysis (HD) patients. A systematic literature search was conducted using Ovid MEDLINE, EBM Reviews-Cochrane Central Register of Controlled Trials, and EBM Reviews-Cochrane Database of Systematic Reviews to identify reported cases of PD patients with calciphylaxis who received STS. The search covered the inception of the databases through August 2022. Across 19 articles, this review identified 30 PD patients with calciphylaxis who received STS. These included 15 case reports, 2 case series, and 2 cohort studies. The administration routes and doses varied depending on the study. For intravenous (IV) administration ( = 18), STS doses ranged from 3.2 g twice daily to 25 g three times weekly for 5 weeks to 8 months. Outcomes included 44% of patients experiencing successful wound healing, 6% discontinuing STS due to adverse effects, 67% transitioning to HD, and 50% dying from calciphylaxis complications. For intraperitoneal (IP) administration ( = 5), STS doses ranged from 12.5 to 25 g three to four times weekly for 12 h to 3 months. Results showed 80% of patients achieving successful wound healing, 80% discontinuing STS due to adverse effects, 40% transitioning to HD, and 20% dying from IP STS-related chemical peritonitis. In cases where patients switched from IV to IP STS ( = 3), doses ranged from 12.5 to 25 g two to three times weekly for 2.5 to 5 months. Among them, 67% experienced successful wound healing, while 33% died from sepsis. Two cases utilized oral STS at a dose of 1500 mg twice daily for 6 and 11 months, resulting in successful wound healing without adverse effects or need for HD. However, one patient (50%) died due to small bowel obstruction. This systematic review provides an overview of STS treatment for PD patients with calciphylaxis. Although successful treatment cases exist, adverse effects were significant. Further research, including larger clinical studies and pharmacokinetic data, is necessary to establish the optimal route, dose, and efficacy of STS in PD patients.
Topics: Humans; Calciphylaxis; Peritoneal Dialysis; Renal Dialysis
PubMed: 37512116
DOI: 10.3390/medicina59071306 -
PloS One 2023To date, isoniazid mono-resistant tuberculosis (TB) is becoming an emerging global public health problem. It is associated with poor treatment outcome. Different studies... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To date, isoniazid mono-resistant tuberculosis (TB) is becoming an emerging global public health problem. It is associated with poor treatment outcome. Different studies have assessed the treatment outcome of isoniazid mono-resistant TB cases, however, the findings are inconsistent and there is limited global comprehensive report. Thus, this study aimed to assess the poor treatment outcome and its associated risk factors among patients with isoniazid mono-resistant TB.
METHODS
Studies that reported the treatment outcomes and associated factors among isoniazid mono-resistant TB were searched from electronic databases and other sources. We used Joana Briggs Institute critical appraisal tool to assess the study's quality. We assessed publication bias through visual inspection of the funnel plot and confirmed by Egger's regression test. We used STATA version 17 for statistical analysis.
RESULTS
Among 347 studies identified from the whole search, data were extracted from 25 studies reported from 47 countries. The pooled successful and poor treatment outcomes were 78% (95%CI; 74%-83%) and 22% (95%CI; 17%-26%), respectively. Specifically, complete, cure, treatment failure, mortality, loss to follow-up and relapse rates were 34%(95%CI; 17%-52%), 62% (95%CI; 50%-73%), 5% (95%CI; 3%-7%), 6% (95%CI; 4%-8%), 12% (95%CI; 8%-17%), and 1.7% (95%CI; 0.4%-3.1%), respectively. Higher prevalence of pooled poor treatment outcome was found in the South East Asian Region (estimate; 40%, 95%C; 34%-45%), and African Region (estimate; 33%, 95%CI; 24%-42%). Previous TB treatment (OR; 1.74, 95%CI; 1.15-2.33), having cancer (OR; 3.53, 95%CI; 1.43-5.62), and being initially smear positive (OR; 1.26, 95%CI; 1.08-1.43) were associated with poor treatment outcome. While those patients who took rifampicin in the continuation phase (OR; 0.22, 95%CI; 0.04-0.41), had extrapulmonary TB (OR; 0.70, 95%CI; 0.55-0.85), and took second-line injectable drugs (OR; 0.54, 95%CI; 0.33-0.75) had reduced risk of poor treatment outcome.
CONCLUSION
Isoniazid mono-resistant TB patients had high poor treatment outcome. Thus, determination of isoniazid resistance pattern for all bacteriologically confirmed TB cases is critical for successful treatment outcome. PROSPERO registration number: CRD42022372367.
Topics: Humans; Isoniazid; Antitubercular Agents; Tuberculosis, Multidrug-Resistant; Risk Factors; Treatment Outcome
PubMed: 37467275
DOI: 10.1371/journal.pone.0286194 -
Tuberculosis (Edinburgh, Scotland) Jul 2023Therapeutic drug monitoring (TDM) is recommended for medications with high inter-individual variability, narrow therapeutic index drugs, possible drug-drug interactions,... (Review)
Review
Therapeutic drug monitoring (TDM) is recommended for medications with high inter-individual variability, narrow therapeutic index drugs, possible drug-drug interactions, drug toxicity, and subtherapeutic concentrations, as well as to assess noncompliance. The area under the plasma concentration-time curve (AUC) is a significant pharmacokinetic parameter since it calculates the drug's total systematic exposure in the body. However, multiple blood samples from the patient are required to calculate the area under the curve, which is inconvenient for both the patient and the healthcare professional. To alleviate the issue, the limited sampling strategy (LSS) was devised, in which sampling is minimized while obtaining complete and precise findings to anticipate the area under the curve. One can reduce costs, labor, and discomfort for patients and healthcare workers by applying this limited sampling strategy. This article examines a systematic evaluation of all the limited sampling done in anti-tuberculosis (anti-TB) medications resulting from the literature search of several research papers. This article also briefly describes the two methodologies: Multiple regression analysis (MRA) and the Bayesian approach used to develop a limited sampling strategy model. Anti-TB medications have been found to have considerable inter-individual variability, and isoniazid has a narrow therapeutic index, both of which are criteria for therapeutic drug monitoring. To avoid multi-drug resistance and therapy failure, it is proposed that limited sampling strategy-based therapeutic drug monitoring of anti-TB medications be undertaken to generate an individualized dose regimen, particularly for individuals at high risk of treatment failure or delayed response.
Topics: Humans; Antitubercular Agents; Drug Monitoring; Bayes Theorem; Feasibility Studies; Mycobacterium tuberculosis; Tuberculosis; Area Under Curve
PubMed: 37429151
DOI: 10.1016/j.tube.2023.102367 -
International Journal of Antimicrobial... Sep 2023Pyrazinamide (PZA) is a first-line antituberculosis drug with potent sterilising activity. Variability in drug exposure may translate into suboptimal treatment... (Review)
Review
Pyrazinamide (PZA) is a first-line antituberculosis drug with potent sterilising activity. Variability in drug exposure may translate into suboptimal treatment responses. This systematic review, conducted according to PRISMA guidelines, aimed to evaluate the concentration-effect relationship. In vitro/in vivo studies had to contain information on the infection model, PZA dose and concentration, and microbiological outcome. Human studies had to present information on PZA dose, measures of drug exposure and maximum concentration, and microbiological response parameter or overall treatment outcome. A total of 34 studies were assessed, including in vitro (n = 2), in vivo (n = 3) and clinical studies (n = 29). Intracellular and extracellular models demonstrated a direct correlation between PZA dose of 15-50 mg/kg/day and reduction in bacterial count between 0.50-27.7 log CFU/mL. Consistent with this, higher PZA doses (>150 mg/kg) were associated with a greater reduction in bacterial burden in BALB/c mice models. Human pharmacokinetic studies displayed a linear positive correlation between PZA dose (i.e. 21.4-35.7 mg/kg/day) and drug exposure (AUC range 220.6-514.5 mg·h/L). Additionally, human studies confirmed a dose-effect relationship, with an increased 2-month sputum culture conversion rate at AUC/MIC targets of 8.4-11.3 with higher exposure/susceptibility ratios leading to greater efficacy. A 5-fold variability in AUC was observed at PZA dose of 25 mg/kg. A direct concentration-effect relationship and increased treatment efficacy with higher PZA exposure to susceptibility ratios was observed. Taking into account variability in drug exposure and treatment response, further studies on dose optimisation are justified.
Topics: Animals; Mice; Humans; Pyrazinamide; Mycobacterium tuberculosis; Tuberculosis; Antitubercular Agents; Mice, Inbred BALB C; Microbial Sensitivity Tests
PubMed: 37419292
DOI: 10.1016/j.ijantimicag.2023.106914 -
The Journal of Infection Sep 2023Historically, extensively drug-resistant tuberculosis has been notoriously difficult to treat with devasting outcomes. As we are coming to the end of an era where the... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Historically, extensively drug-resistant tuberculosis has been notoriously difficult to treat with devasting outcomes. As we are coming to the end of an era where the 2006 extensively drug-resistant tuberculosis definitions and old treatment regimens are being replaced, we aimed to estimate the proportion of extensively drug-resistant tuberculosis patients globally who achieved successful treatment outcomes.
METHODS
We conducted a systematic review of PubMed/MEDLINE, Scopus, Web of Science, and Embase from January 1, 2005, through April 3, 2023. Included studies reported WHO treatment outcomes, or adaptions hereof, for pre-extensively and/or extensively drug-resistant tuberculosis patients according to the 2006 WHO definition. Eligible studies included cohorts of at least 10 adults (aged>18 years) that were not pregnant. Using a random-effects model, we calculated pooled proportions of treatment outcomes and performed sensitivity and subgroup analyses. PROSPERO registration number: CRD42022340961.
RESULTS
Among 5056 studies reviewed, we identified 94 studies from 26 countries, involving 10,223 extensively drug-resistant tuberculosis patients. The pooled proportion of successful treatment outcomes was 44.2% (95%CI: 38.3-50.3). Sensitivity analyses consistently produced similar estimates. A slight improvement in treatment outcomes was observed after 2013. Furthermore, 25 studies reported outcomes for 3564 individuals with pre-extensively drug-resistant tuberculosis, of which 63.3% achieved successful treatment (95%CI: 43.1-72.5).
CONCLUSION
Globally, the success rate of extensively drug-resistant tuberculosis treatment is 44.2%, far below the WHO's target rate of 75%. These results may serve as a reference for future studies assessing extensively drug-resistant tuberculosis treatment outcomes under the 2021 definition treated with better treatment regimens available. Comprehensive surveillance data of extensively drug-resistant tuberculosis outcomes from the whole world are desirable to monitor treatment progress.
Topics: Humans; Adult; Pregnancy; Female; Extensively Drug-Resistant Tuberculosis; Tuberculosis, Pulmonary; Treatment Outcome; Tuberculosis, Multidrug-Resistant; Antitubercular Agents
PubMed: 37356629
DOI: 10.1016/j.jinf.2023.06.014