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Journal of Global Antimicrobial... May 2024Tuberculosis (TB), one of the deadliest infectious diseases globally, is increasingly exacerbated in China by the emergence of resistant Mycobacterium tuberculosis (MTB)... (Review)
Review
BACKGROUND
Tuberculosis (TB), one of the deadliest infectious diseases globally, is increasingly exacerbated in China by the emergence of resistant Mycobacterium tuberculosis (MTB) strains. Drug-resistant TB, including mono-drug resistant TB, multidrug-resistant TB (MDR-TB), and extensively drug-resistant TB (XDR-TB), presents significant public health challenges.
METHODS
We conducted a systematic literature review from January 2010 to February 2024 using databases such as PubMed, Embase, Web of Science, and Google Scholar. Our focus was on empirical data related to drug resistance patterns in newly diagnosed TB cases. Non-empirical studies were excluded through meticulous filtering. For meta-analysis, we used Review Manager (RevMan) 5.2 and assessed evidence quality using the Newcastle-Ottawa Scale (NOS).
RESULTS
Our search strategy identified 40 studies that met the inclusion criteria, encompassing a total sample size of 87,667 participants. Among new TB cases, the estimated prevalence of MDR-TB in China was 6.9% (95% CI: 5.6-8.1%). Prevalence rates for mono-drug resistance to first-line anti-TB medications were as follows: isoniazid at 18.2% (95% CI: 16.4-20.6%), rifampicin at 10.5% (95% CI: 8.6-12.8%), and ethambutol at 5.7% (95% CI: 4.1-7.3%). The prevalence of streptomycin resistance, a former first-line anti-TB drug, was 17.1% (95% CI: 14.6-19.1%). The prevalence of other types of mono-drug resistance was 15.2% (95% CI: 13.9-17.3%), and for XDR-TB, it was 0.9% (95% CI: 0.6-1.4%).
CONCLUSIONS
The high prevalence of drug-resistant TB in China poses a significant public health challenge. There is an urgent need for targeted interventions and continued surveillance to combat the spread of drug-resistant TB.
PubMed: 38825149
DOI: 10.1016/j.jgar.2024.05.018 -
Neurosurgical Review May 2024Cerebral cavernous malformations (CCMs) are cerebral vascular lesions that occasionally occur with seizures. We present a retrospective case series from IRCCS Gaslini... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Cerebral cavernous malformations (CCMs) are cerebral vascular lesions that occasionally occur with seizures. We present a retrospective case series from IRCCS Gaslini Children's Hospital, a systematic review, and meta-analysis of the literature with the goal of elucidating the post-surgery seizure outcome in children with CCMs.
METHODS
a retrospective review of children with cavernous malformation related epilepsy who underwent surgery at Gaslini Children's Hospital from 2005 to 2022 was conducted. We also conducted a comprehensive search on PubMed/MEDLINE and Scopus databases from January 1989 to August 2022. Inclusion criteria were: presence of CCMs-related epilepsy, in under 18 years old subjects with a clear lesion site. Presence of post-surgery seizure outcome and follow-up ≥ 12 months.
RESULTS
we identified 30 manuscripts and 223 patients with CCMs-related epilepsy, including 17 patients reported in our series. We identified 85.7% Engel class I subjects. The risk of expected neurological deficits was 3.7%; that of unexpected neurological deficits 2.8%. We found no statistically significant correlations between Engel class and the following factors: site of lesion, type of seizure, drug resistance, duration of disease, type of surgery, presence of multiple CCMs. However, we found some interesting trends: longer disease duration and drug resistance seem to be more frequent in subjects in Engel class II, III and IV; multiple cavernomas would not seem to influence seizure outcome.
CONCLUSIONS
epilepsy surgery in children with CCMs is a safe and successful treatment option. Further studies are necessary to define the impact of clinical features on seizure prognosis.
Topics: Adolescent; Child; Child, Preschool; Female; Humans; Male; Epilepsy; Hemangioma, Cavernous, Central Nervous System; Neurosurgical Procedures; Retrospective Studies; Seizures; Treatment Outcome; Infant
PubMed: 38819574
DOI: 10.1007/s10143-024-02491-0 -
The Lancet. Infectious Diseases May 2024Targeted next-generation sequencing (NGS) can rapidly and simultaneously detect mutations associated with resistance to tuberculosis drugs across multiple gene targets....
BACKGROUND
Targeted next-generation sequencing (NGS) can rapidly and simultaneously detect mutations associated with resistance to tuberculosis drugs across multiple gene targets. The use of targeted NGS to diagnose drug-resistant tuberculosis, as described in publicly available data, has not been comprehensively reviewed. We aimed to identify targeted NGS assays that diagnose drug-resistant tuberculosis, determine how widely this technology has been used, and assess the diagnostic accuracy of these assays.
METHODS
In this systematic review and meta-analysis, we searched MEDLINE, Embase, Cochrane Library, Web of Science Core Collection, Global Index Medicus, Google Scholar, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform for published and unpublished reports on targeted NGS for drug-resistant tuberculosis from Jan 1, 2005, to Oct 14, 2022, with updates to our search in Embase and Google Scholar until Feb 13, 2024. Studies eligible for the systematic review described targeted NGS approaches to predict drug resistance in Mycobacterium tuberculosis infections using primary samples, reference strain collections, or cultured isolates from individuals with presumed or confirmed tuberculosis. Our search had no limitations on study type or language, although only reports in English, German, and French were screened for eligibility. For the meta-analysis, we included test accuracy studies that used any reference standard, and we assessed risk of bias using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The primary outcomes for the meta-analysis were sensitivity and specificity of targeted NGS to diagnose drug-resistant tuberculosis compared to phenotypic and genotypic drug susceptibility testing. We used a Bayesian bivariate model to generate summary receiver operating characteristic plots and diagnostic accuracy measures, overall and stratified by drug and sample type. This study is registered with PROSPERO, CRD42022368707.
FINDINGS
We identified and screened 2920 reports, of which 124 were eligible for our systematic review, including 37 review articles and 87 reports of studies collecting samples for targeted NGS. Sequencing was mainly done in the USA (14 [16%] of 87), western Europe (ten [11%]), India (ten [11%]), and China (nine [10%]). We included 24 test accuracy studies in the meta-analysis, in which 23 different tuberculosis drugs or drug groups were assessed, covering first-line drugs, injectable drugs, and fluoroquinolones and predominantly comparing targeted NGS with phenotypic drug susceptibility testing. The combined sensitivity of targeted NGS across all drugs was 94·1% (95% credible interval [CrI] 90·9-96·3) and specificity was 98·1% (97·0-98·9). Sensitivity for individual drugs ranged from 76·5% (52·5-92·3) for capreomycin to 99·1% (98·3-99·7) for rifampicin; specificity ranged from 93·1% (88·0-96·3) for ethambutol to 99·4% (98·3-99·8) for amikacin. Diagnostic accuracy was similar for primary clinical samples and culture isolates overall and for rifampicin, isoniazid, ethambutol, streptomycin, and fluoroquinolones, and similar after excluding studies at high risk of bias (overall sensitivity 95·2% [95% CrI 91·7-97·1] and specificity 98·6% [97·4-99·3]).
INTERPRETATION
Targeted NGS is highly sensitive and specific for detecting drug resistance across panels of tuberculosis drugs and can be performed directly on clinical samples. There is a paucity of data on performance for some currently recommended drugs. The barriers preventing the use of targeted NGS to diagnose drug-resistant tuberculosis in high-burden countries need to be addressed.
FUNDING
National Institutes of Allergy and Infectious Diseases and Swiss National Science Foundation.
PubMed: 38795712
DOI: 10.1016/S1473-3099(24)00263-9 -
The Journal of Infection Jul 2024The COVID-19 pandemic has posed a significant threat to the global healthcare system, presenting a major challenge to antimicrobial stewardship worldwide. This study... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The COVID-19 pandemic has posed a significant threat to the global healthcare system, presenting a major challenge to antimicrobial stewardship worldwide. This study aimed to provide a comprehensive and up-to-date picture of global antimicrobial resistance (AMR) and antibiotic use in COVID-19 patients.
METHODS
We conducted a systematic review to determine the prevalence of AMR and antibiotic usage among COVID-19 patients receiving treatment in healthcare facilities. Our search encompassed the PubMed, Web of Science, Embase, and Scopus databases, spanning studies published from December 2019 to May 2023. We utilized random-effects meta-analysis to assess the prevalence of multidrug-resistant organisms (MDROs) and antibiotic use in COVID-19 patients, aligning with both the WHO's priority list of MDROs and the AWaRe list of antibiotic products. Estimates were stratified by region, country, and country income. Meta-regression models were established to identify predictors of MDRO prevalence and antibiotic use in COVID-19 patients. The study protocol was registered with PROSPERO (CRD 42023449396).
RESULTS
Among the 11,050 studies screened, 173 were included in the review, encompassing a total of 892,312 COVID-19 patients. MDROs were observed in 42.9% (95% CI 31.1-54.5%, I = 99.90%) of COVID-19 patients: 41.0% (95% CI 35.5-46.6%) for carbapenem-resistant organisms (CRO), 19.9% (95% CI 13.4-27.2%) for methicillin-resistant Staphylococcus aureus (MRSA), 24.9% (95% CI 16.7-34.1%) for extended-spectrum beta-lactamase-producing organisms (ESBL), and 22.9% (95% CI 13.0-34.5%) for vancomycin-resistant Enterococcus species (VRE), respectively. Overall, 76.2% (95% CI 69.5-82.9%, I = 99.99%) of COVID-19 patients were treated with antibiotics: 29.6% (95% CI 26.0-33.4%) with "Watch" antibiotics, 22.4% (95% CI 18.0-26.7%) with "Reserve" antibiotics, and 16.5% (95% CI 13.3-19.7%) with "Access" antibiotics. The MDRO prevalence and antibiotic use were significantly higher in low- and middle-income countries than in high-income countries, with the lowest proportion of antibiotic use (60.1% (95% CI 52.1-68.0%)) and MDRO prevalence (29.1% (95% CI 21.8-36.4%)) in North America, the highest MDRO prevalence in the Middle East and North Africa (63.9% (95% CI 46.6-81.2%)), and the highest proportion of antibiotic use in South Asia (92.7% (95% CI 90.4-95.0%)). The meta-regression identified antibiotic use and ICU admission as a significant predictor of higher prevalence of MDROs in COVID-19 patients.
CONCLUSIONS
This systematic review offers a comprehensive and current assessment of MDRO prevalence and antibiotic use among COVID-19 patients in healthcare facilities. It underscores the formidable challenge facing global efforts to prevent and control AMR amidst the backdrop of the COVID-19 pandemic. These findings serve as a crucial warning to policymakers, highlighting the urgent need to enhance antimicrobial stewardship strategies to mitigate the risks associated with future pandemics.
Topics: Humans; Anti-Bacterial Agents; COVID-19; Antimicrobial Stewardship; SARS-CoV-2; Health Facilities; Drug Resistance, Multiple, Bacterial; Global Health; Prevalence; Methicillin-Resistant Staphylococcus aureus
PubMed: 38754635
DOI: 10.1016/j.jinf.2024.106183 -
International Journal of Molecular... May 2024Multiple myeloma (MM), the second most common hematologic malignancy, remains incurable, and its incidence is rising. Chimeric Antigen Receptor T-cell (CAR-T cell)... (Meta-Analysis)
Meta-Analysis Review
An Assessment of the Effectiveness and Safety of Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma Patients with Relapsed or Refractory Disease: A Systematic Review and Meta-Analysis.
Multiple myeloma (MM), the second most common hematologic malignancy, remains incurable, and its incidence is rising. Chimeric Antigen Receptor T-cell (CAR-T cell) therapy has emerged as a novel treatment, with the potential to improve the survival and quality of life of patients with relapsed/refractory multiple myeloma (rrMM). In this systematic review and meta-analysis, conducted in accordance with PRISMA guidelines, we aim to provide a concise overview of the latest developments in CAR-T therapy, assess their potential implications for clinical practice, and evaluate their efficacy and safety outcomes based on the most up-to-date evidence. A literature search conducted from 1 January 2019 to 12 July 2023 on Medline/PubMed, Scopus, and Web of Science identified 2273 articles, of which 29 fulfilled the specified criteria for inclusion. Our results offer robust evidence supporting CAR-T cell therapy's efficacy in rrMM patients, with an encouraging 83.21% overall response rate (ORR). A generally safe profile was observed, with grade ≥ 3 cytokine release syndrome (CRS) at 7.12% and grade ≥ 3 neurotoxicity at 1.37%. A subgroup analysis revealed a significantly increased ORR in patients with fewer antimyeloma regimens, while grade ≥ 3 CRS was more common in those with a higher proportion of high-risk cytogenetics and prior exposure to BCMA therapy.
Topics: Multiple Myeloma; Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Treatment Outcome; Quality of Life; Neoplasm Recurrence, Local; Cytokine Release Syndrome
PubMed: 38732213
DOI: 10.3390/ijms25094996 -
Infection and Drug Resistance 2024The World Health Organization (WHO) has classified carbapenem-resistant (), and () as high-priority pathogens, and carbapenem-resistant bacteria (CRB) have been... (Review)
Review
BACKGROUND
The World Health Organization (WHO) has classified carbapenem-resistant (), and () as high-priority pathogens, and carbapenem-resistant bacteria (CRB) have been reported to spread between humans, animals, and the environment.
OBJECTIVE
This study aimed to conduct a systematic review of carbapenem resistance in animals, foods, and the environment on the African continent and to provide recommendations and perspectives for better prevention and control of carbapenem resistance in Africa.
RESULTS
A total of 137 research articles collected from 2009 to 2023 were selected for this review, including articles reporting carbapenem-resistant bacteria in animals (81/137; 59.1%), the environment (66/137; 48.2%), and foods (26/137; 19%). Carbapenem-resistant bacterial species belonged to 31 genera and 17 families, including mainly spp. (68/127; 53.5%); spp. (45/127; 35.4%); spp. (20/127; 15.7%), spp. (19/127; 15%) and spp. (15/127; 11.8%). The prevalence of CRBs by country ranged from 1.1% to 48.5%, and the pooled prevalence of CRBs isolated from animal-environment-food in Africa was 19.1% (2804/14,684; Standard Deviation = 15). Twenty carbapenemase families belonging to A, B, C, and D Ambler classes were reported, including mainly carbapenemase genes from (44/84; 52.4%), (34/84; 40.5%), (23/84; 27.4%), (22/84; 26.2%), (19/84; 22.6%), and (12/84; 14.3%) families. The reported mobile genetic elements (MGE) carrying carbapenemase-encoding genes included plasmids (16/19; 84.2%), integrons (3/19; 15.8%), transposons (3/19; 15.8%), and insertion sequences (2/19; 10.5%). was often carried by (60kb-65kb) IncL/M-type pOXA-48 plasmids, while was often carried by (45-50kb) IncX-type plasmids. Moreover, 25 articles investigated and reported virulent and hypervirulent CRBs that carried multiple virulence factors.
CONCLUSION
Animal-environment-food ecosystems would constitute reservoirs of CRBs involved in human infections. The One Health approach and constant collaboration between governments are necessary to drastically reduce the mortality rates linked to antimicrobial resistance.
PubMed: 38715963
DOI: 10.2147/IDR.S458317 -
The Journal of Hospital Infection Jul 2024Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Acinetobacter baumannii infections pose challenges for clinical treatment and cause high mortality,... (Meta-Analysis)
Meta-Analysis Review
Risk factors for multidrug-resistant and extensively drug-resistant Acinetobacter baumannii infection of patients admitted in intensive care unit: a systematic review and meta-analysis.
BACKGROUND
Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Acinetobacter baumannii infections pose challenges for clinical treatment and cause high mortality, particularly in intensive care units (ICUs).
AIM
To systematically summarize and analyse the risk factors for MDR/XDR A. baumannii-infected patients admitted to ICUs.
METHODS
PubMed, Embase, Web of Science, and the Cochrane Library were searched for eligible original studies published in English before October 2023. Meta-analysis was conducted where appropriate, with mean differences (MDs) and odds ratios (ORs) calculated for continuous and nominal scaled data. The quality of included studies was assessed using the Newcastle-Ottawa Scale (NOS).
FINDINGS
Ten studies reporting 1199 ICU patients (604 from general ICUs, 435 from neonatal ICUs, and 160 from paediatric ICUs) from eight countries were included in our analysis. Risk factors associated with MDR A. baumannii infection among patients admitted to general ICUs included high Acute Physiology And Clinical Health II (APACHE Ⅱ) score (mean difference (MD): 7.52; 95% confidence interval (CI): 3.24-11.80; P = 0.0006), invasive procedures (odds ratio (OR): 3.47; 95% CI: 1.70-7.10; P = 0.0006), longer ICU stay (MD: 3.40; 95% CI: 2.94-3.86; P < 0.00001), and use of antibiotics (OR: 2.69; 95% CI: 1.22-5.94; P = 0.01). In the sub-group analysis, longer neonatal ICU stay (MD: 16.88; 95% CI: 9.79-23.97; P < 0.00001) was associated with XDR A. baumannii infection.
CONCLUSION
Close attention should be paid to patients with longer ICU stays, undergoing invasive procedures, using antibiotics, and with high APACHE Ⅱ scores to reduce the risk of MDR and XDR A. baumannii infections.
Topics: Humans; Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Multiple, Bacterial; Intensive Care Units; Risk Factors
PubMed: 38710306
DOI: 10.1016/j.jhin.2024.04.013 -
Frontiers in Public Health 2024The continuing spread of tuberculosis (TB) worldwide, especially drug-resistant TB, poses a major challenge to healthcare systems globally. Addressing this requires...
OBJECTIVES
The continuing spread of tuberculosis (TB) worldwide, especially drug-resistant TB, poses a major challenge to healthcare systems globally. Addressing this requires appraising the cost effectiveness of existing pharmacological interventions against TB to identify key drivers of cost effectiveness and value and guide pharmaceutical innovation and novel drug regimen development.
METHODS
Studies were identified from a search of six database: MEDLINE MEDLINE-In Process, MEDLINE Epub Ahead of Print, EMBASE, Cochrane Database of Systematic Reviews, and Econlit in July 2022. Two reviewers independently assessed all identified studies and reports using pre-defined inclusion/exclusion criteria. Study methodological quality was assessed, data were extracted in standard tables, and results were narratively synthesized.
RESULTS
Overall, 991 studies and 53 HTA reports were identified with 20 studies and 3 HTA reports meeting the inclusion criteria. Quality assessment of the 20 studies identified 4 with minor limitations, while the remainder were assessed as having potentially or very serious limitations. Sixteen studies conducted cost-utility analyses, 6 conducted cost-effectiveness analyses, and 2 conducted cost-comparison analyses with some studies performing multiple analyses. The majority (n = 16) were model-based. Eleven studies analyzed the cost-effectiveness of bedaquiline, 6 compared shorter to longer/standard duration regimens, 2 assessed ethambutol, and 1 assessed delamanid. Key drivers of cost effectiveness were drug costs, the number of TB cases, the portion of cases with sputum culture conversion, treatment delivery costs, and treatment efficacy. Common value elements considered included adverse events, drug resistance, and improving treatment adherence.
CONCLUSION
Our results suggest that out of the pharmacological treatments assessed, bedaquiline is likely a cost-effective addition to existing treatment regimens/background treatment regimens, while ethambutol is not likely to be. Newer shorter regimens, even if more costly, seem to be more cost-effective compared to longer regimens. These results illustrate the limited number of novel cost-effective pharmacological interventions and highlight a need to develop new drugs/regimens against TB to overcome resistance, taking into account the key drivers of cost effectiveness and other value attributes identified from this review.
Topics: Humans; Cost-Benefit Analysis; Antitubercular Agents; Tuberculosis; Tuberculosis, Multidrug-Resistant
PubMed: 38689771
DOI: 10.3389/fpubh.2024.1201512 -
The Journal of Hospital Infection Jun 2024The optimal duration of therapy for Pseudomonas aeruginosa bloodstream infection (PSA-BSI) is unknown, with prolonged therapy frequently favored due to severity of... (Meta-Analysis)
Meta-Analysis Comparative Study
The optimal duration of therapy for Pseudomonas aeruginosa bloodstream infection (PSA-BSI) is unknown, with prolonged therapy frequently favored due to severity of infection, patient complexity, risk of multi-drug resistance, and high mortality. We therefore conducted a systematic review and meta-analysis of studies with head-to-head comparison of short versus prolonged therapy for PSA-BSI. A comprehensive search including Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus was performed. We pooled risk ratios using DerSimonian-Laird random effects model and performed subgroup analysis of outcomes including all-cause mortality, recurrent infection, and composite of these outcomes among patients receiving short versus prolonged therapy for PSA-BSI. Heterogeneity was assessed by the I-index. Risk of bias for cohort studies was assessed using ROBINS-I tool. Of the 908 identified studies, six were included in the systematic review and five studies with head-to-head comparison of treatment duration were assessed in the meta-analysis, totalling 1746 patients. No significant difference in propensity score-weighted composite outcome (30-day all-cause mortality or recurrent infection) was noted between patients receiving short or prolonged therapy, with a pooled RR risk ratio of 0.80 (95% CI confidence interval 0.51-1.25, P=0.32; I = 0%). Additionally, duration of therapy did not impact individual outcomes of 30-day all-cause mortality or recurrent/persistent infection. Our meta-analysis demonstrated that short duration of antimicrobial therapy may have similar efficacy to prolonged treatment for PSA-BSI. Future randomized trials will be necessary to definitively determine optimal management of PSA bacteraemia.
Topics: Humans; Pseudomonas Infections; Bacteremia; Pseudomonas aeruginosa; Anti-Bacterial Agents; Treatment Outcome; Duration of Therapy; Survival Analysis; Time Factors
PubMed: 38685414
DOI: 10.1016/j.jhin.2024.04.007 -
Journal of Epidemiology and Global... Jun 2024Due to the rising incidence of multidrug-resistant (MDR) pathogens, especially in Low-Middle-Income Countries (LMIC), post-partum infections represent a significant... (Review)
Review
BACKGROUND
Due to the rising incidence of multidrug-resistant (MDR) pathogens, especially in Low-Middle-Income Countries (LMIC), post-partum infections represent a significant treatment challenge.
METHODS
We performed a systematic review of the literature from January 2005 to February 2023 to quantify the frequency of maternal post-partum infections due to MDR pathogens in LMICs, focusing on methicillin-resistant Staphylococcus aureus (MRSA) and/or extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales.
SECONDARY OBJECTIVES
description of antimicrobials' prescriptions.
FINDINGS
We included 22 studies with 14,804 total bacterial isolates from 12 countries, mostly from WHO African-Region. Twelve papers described wound- and 10 puerperal-infections. Seven were high-quality articles. Seventeen studies reported data on MRSA, and 18 on ESBL-producing Enterobacterales. Among high-quality studies, MRSA ranged from 9.8% in Ghana to 91.2% in Uganda; ESBL-producing Enterobacterales ranged from 22.8% in Ukraine to 95.2% in Uganda. Nine articles, mostly on C-sections, described different protocols for antibiotic prophylaxis and/or post-partum treatment.
INTERPRETATION
We described a high burden of post-partum infections caused by MRSA and/or ESBL-producing Enterobacterales in LMICs, but only a few studies met quality standards. There is an urgent need for high-quality studies to better describe the real burden of antimicrobial resistance in low-resource settings and inform policies to contain the spread of multidrug-resistant organisms.
Topics: Humans; Female; Developing Countries; Puerperal Infection; Methicillin-Resistant Staphylococcus aureus; Anti-Bacterial Agents; Pregnancy; Drug Resistance, Multiple, Bacterial; Staphylococcal Infections; Postpartum Period
PubMed: 38630391
DOI: 10.1007/s44197-024-00222-8