-
Euro Surveillance : Bulletin Europeen... May 2023BackgroundAntimicrobial resistance (AMR) is of public health concern worldwide.AimWe aimed to summarise the German AMR situation for clinicians and... (Meta-Analysis)
Meta-Analysis
BackgroundAntimicrobial resistance (AMR) is of public health concern worldwide.AimWe aimed to summarise the German AMR situation for clinicians and microbiologists.MethodsWe conducted a systematic review and meta-analysis of 60 published studies and data from the German (ARS). Primary outcomes were AMR proportions in bacterial isolates from infected patients in Germany (2016-2021) and the case fatality rates (2010-2021). Random and fixed (common) effect models were used to calculate pooled proportions and pooled case fatality odds ratios, respectively.ResultsThe pooled proportion of meticillin resistance in infections (MRSA) was 7.9% with a declining trend between 2014 and 2020 (odds ratio (OR) = 0.89; 95% CI: 0.886-0.891; p < 0.0001), while vancomycin resistance in (VRE) bloodstream infections increased (OR = 1.18; (95% CI: 1.16-1.21); p < 0.0001) with a pooled proportion of 34.9%. Case fatality rates for MRSA and VRE were higher than for their susceptible strains (OR = 2.29; 95% CI: 1.91-2.75 and 1.69; 95% CI: 1.22-2.33, respectively). Carbapenem resistance in Gram-negative pathogens (, , spp. and ) was low to moderate (< 9%), but resistance against third-generation cephalosporins and fluoroquinolones was moderate to high (5-25%). exhibited high resistance against carbapenems (17.0%; 95% CI: 11.9-22.8), third-generation cephalosporins (10.1%; 95% CI: 6.6-14.2) and fluoroquinolones (24.9%; 95% CI: 19.3-30.9). Statistical heterogeneity was high (I2 > 70%) across studies reporting resistance proportions.ConclusionContinuous efforts in AMR surveillance and infection prevention and control as well as antibiotic stewardship are needed to limit the spread of AMR in Germany.
Topics: Humans; Anti-Bacterial Agents; Drug Resistance, Bacterial; Microbial Sensitivity Tests; Methicillin-Resistant Staphylococcus aureus; Fluoroquinolones; Germany; Escherichia coli; Cephalosporins
PubMed: 37199987
DOI: 10.2807/1560-7917.ES.2023.28.20.2200672 -
Alimentary Pharmacology & Therapeutics Jul 2015Half-dose regimens may be equally effective but associated with diminished adverse events (AE) than standard-dose regimens. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Half-dose regimens may be equally effective but associated with diminished adverse events (AE) than standard-dose regimens.
AIM
To assess efficacy and safety of full- vs. half-dose clarithromycin in the treatment of H. pylori.
METHODS
Medline, EMBASE and PubMed databases were searched for randomised controlled trials (RCTs) that meet eligibility criteria. Only parallel group RCTs with ≥ 2 arms were eligible. Studies comparing triple, quadruple or sequential therapy for 7-14 days were selected. Regimens had to contain the same drug combination, differing only in dosage; the comparison of full- vs. half-dose clarithromycin was required, regardless if other drugs were dose-reduced or not. Data extraction was performed for primary outcome [eradication by intent-to-treat (ITT) and per-protocol (PP) analyses] and secondary outcome (AE).
RESULTS
A total of 1622 articles were identified, of which 19 studies were eligible. Overall, eradication was achieved in 82.5% of half-dose (n = 2115) vs. 83.4% of full-dose recipients (n = 2109) on ITT (87.1% vs. 88.4% on PP respectively). Pooled relative risk in the half- vs. full-dose regimen was 0.98 (95% CI: 0.95-1.02) on ITT and 0.99 (95% CI: 0.97-1.01) on PP by the random effects model. Heterogeneity was significant (chi-squared statistic P = 0.05, I(2) = 37%). AE were reported in 29.3% of half- vs. 44.0% of full-dose recipients [pooled RR 0.67 (95% CI: 0.60-0.75)]. Pre-planned subgroup analyses of dose modification, sample size, study origin and treatment duration, as well as sensitivity analysis showed no significant differences between arms.
CONCLUSION
A half-dose clarithromycin-based regimen is equally effective yet better tolerated than its full-dose counterpart in the treatment of H. pylori.
Topics: Anti-Bacterial Agents; Clarithromycin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Randomized Controlled Trials as Topic
PubMed: 26011564
DOI: 10.1111/apt.13259 -
Systematic Reviews Nov 2022Klebsiella pneumoniae is a gram-negative rod belonging to the order Enterobacterales and having a wide distribution in the environment, including the human colon.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Klebsiella pneumoniae is a gram-negative rod belonging to the order Enterobacterales and having a wide distribution in the environment, including the human colon. Recently, the bacterium is one of the known problems in the healthcare setting as it has become resistant to last-resort drugs like carbapenems. The colonized person can serve as a reservoir for his/herself and others, especially in the healthcare setting leading to nosocomial and opportunistic infections. Therefore, we aimed to quantitatively estimate the rate of prevalence and incidence of colonization with carbapenem-resistant K. pneumoniae.
METHODS
A literature search was conducted on PubMed/MEDLINE, Google Scholar, Science Direct, Cochrane Library, WHO Index Medicus, and university databases. The study includes all published and unpublished papers that addressed the prevalence or incidence of K. pneumoniae colonization. Data were extracted onto format in Microsoft Excel and pooled estimates with a 95% confidence interval calculated using Der-Simonian-Laird random-effects model. With the use of I statistics and prediction intervals, the level of heterogeneity was displayed. Egger's tests and funnel plots of standard error were used to demonstrate the publication bias.
RESULTS
A total of 35 studies were included in the review and 32 records with 37,661 patients for assessment of prevalence, while ten studies with 3643 patients for incidence of colonization. The prevalence of carbapenem-resistant K. pneumoniae colonization varies by location and ranges from 0.13 to 22%, with a pooled prevalence of 5.43%. (3.73-7.42). Whereas the incidence of colonization ranges from 2 to 73% with a pooled incidence of 22.3% (CI 12.74-31.87), both prevalence and incidence reports are majorly from developed countries. There was a variation in the distribution of carbapenem resistance genes among colonizing isolates with KPC as a prominent gene reported from many studies and NDM being reported mainly by studies from Asian countries. A univariate meta-regression analysis indicated continent, patient type, study design, and admission ward do not affect the heterogeneity (p value>0.05).
CONCLUSION
The review revealed that colonization with K. pneumoniae is higher in a healthcare setting with variable distribution in different localities, and resistance genes for carbapenem drugs also have unstable distribution in different geographic areas.
Topics: Humans; Carbapenems; Klebsiella pneumoniae; Drug Resistance, Bacterial; Prevalence; Incidence; Anti-Bacterial Agents
PubMed: 36380387
DOI: 10.1186/s13643-022-02110-3 -
Journal of Ethnopharmacology Aug 2015Buruli ulcer (BU) is the third most common mycobacterial infection in the world, after tuberculosis and leprosy and has recently been recognized as an important emerging... (Review)
Review
ETHNOPHARMACOLOGICAL RELEVANCE
Buruli ulcer (BU) is the third most common mycobacterial infection in the world, after tuberculosis and leprosy and has recently been recognized as an important emerging disease. This disease is common in West Africa where more than 99% of the burden is felt and where most affected people live in remote areas with traditional medicine as primary or only option. Reports indicate that the ethnopharmacological control approach of the disease in such settings has shown promise. However, no or very few compilations of traditional knowledge in using medicinal plants to treat BU have been attempted so far. This review aimed to record medicinal plants used traditionally against BU in three countries in West Africa: Ivory Coast, Ghana and Benin and for which ethnopharmacological knowledge supported by pharmacological investigations has been reported. The information recorded in this review will support further pharmacological research to develop appropriate drugs for a better BU control.
MATERIAL AND METHODS
A systematic review of the literature on ethnobotanical use and anti-BU activity of plants reported for BU treatment was performed. The approach consisted to search several resources, including Technical Reports, Books, Theses, Conference proceedings, web-based scientific databases such as publications on PubMed, Science direct, Springer, ACS, Scielo, PROTA, Google and Google scholar reporting ethnobotanical surveys and screening of natural products against Mycobacterium ulcerans. This study was limited to papers and documents published either in English or French reporting ethnopharmacological knowledge in BU treatment or pharmacological potency in vitro. This review covered the available literature up to December 2014.
RESULTS
The majority of reports originated from the three most affected West African countries (Cote d'Ivoire, Ghana and Benin). Though, 98 plant species belonging to 48 families have been identified as having anti-BU use, many have received no or little attention. Most of the pharmacological studies were performed only on 54 species. To a lesser extent, ethnopharmacological knowledge was validated in vitro for only 13 species. Of those, seven species including Ricinus comminus, Cyperus cyperoides (cited as Mariscus alternifolius), Nicotiana tabacum, Mangifera indica, Solanum rugosum, Carica papaya, and Moringa oleifera demonstrated efficacy in hospitalised BU patients. Four isolated and characterized compounds were reported to have moderate bioactivity in vitro against M. ulcerans.
CONCLUSIONS
This review compiles for the first time ethnopharmacologically useful plants against BU. The phamacological potential of 13 of them has been demonstrated in vitro and support BU evidence-based traditional medicines. In addition, 7 species showed activity in BU patients and have emerged as a promising source of the traditional medicine for treatment of BU. Yet, further safety and efficacy study should be initiated prior any approval as alternative therapy. Overall, a huge gap in knowledge appeared, suggesting further well-planned and detailed investigations of the in vitro, in vivo, and safety properties of the claimed anti-BU plants. Therefore, plants with medicinal potential should be scrutinized for biologically active compounds, using bioassay-guided fractionation approach to provide new insights to find novel therapeutics for BU control.
Topics: Africa, Western; Anti-Bacterial Agents; Buruli Ulcer; Ethnopharmacology; Humans; Mycobacterium ulcerans; Plant Preparations; Plants, Medicinal
PubMed: 26099634
DOI: 10.1016/j.jep.2015.06.024 -
European Cells & Materials Oct 2021Osteomyelitis is an inflammatory bone disease caused by an infecting microorganism leading to a gradual bone loss. Due to the difficulty in studying osteomyelitis...
Osteomyelitis is an inflammatory bone disease caused by an infecting microorganism leading to a gradual bone loss. Due to the difficulty in studying osteomyelitis directly in patients, animal models allow researchers to investigate the pathogenesis of the infection and the development of novel prophylactic, anti-inflammatory and antimicrobial treatment strategies. This review is specifically focused on the in vivo mouse osteomyelitis studies available in literature. Thus, a systematic search on Web of Science and PubMed was conducted using the query "(infection) AND (mice OR mouse OR murine) AND (model OR models) AND (arthroplasty OR fracture OR (internal fixator) OR (internal fixation OR prosthesis OR implant OR osteomyelitis)". After critical assessment of the studies according to the inclusion and exclusion criteria, 135 studies were included in the detailed analysis. Based on the model characteristics, the studies were classified into five subject groups: haematogenous osteomyelitis, post-traumatic osteomyelitis, bone-implant-related infection, peri-prosthetic joint infection, fracture-related infection. In addition, the characteristics of the mice used, such as inbred strain, age or gender, the characteristics of the pathogens used, the inoculation methods, the type of anaesthesia and analgesia used during surgery and the procedures for evaluating the pathogenicity of the infecting micro-organism were described. Overall, the mouse is an excellent first step in vivo model to study the pathogenesis, inflammation and healing process of osteomyelitis and to evaluate novel prophylaxis and treatment strategies.
Topics: Animals; Anti-Bacterial Agents; Disease Models, Animal; Humans; Inflammation; Mice; Osteomyelitis; Staphylococcal Infections
PubMed: 34672359
DOI: 10.22203/eCM.v042a22 -
Reviews in Medical Virology Jan 2022Azithromycin (AZM) is commonly used in Covid-19 patients based on low-quality evidence, increasing the risk of developing adverse events and antimicrobial resistance.... (Meta-Analysis)
Meta-Analysis Review
Azithromycin (AZM) is commonly used in Covid-19 patients based on low-quality evidence, increasing the risk of developing adverse events and antimicrobial resistance. The current systematic review and meta-analysis investigated the safety and efficacy of AZM in treating Covid-19 patients using published randomized controlled trials. Google Scholar, PubMed, Scopus, Cochrane Library, Clinical Trials.gov, MEDLINE, bioRxiv and medRxiv were searched for relevant studies. The random-effects model was used to pool estimates using the Paule-Mandel estimate for heterogeneity. The odds ratio and raw difference in medians were used for dichotomous and continuous outcomes, respectively. The analysis included seven studies with 8822 patients (median age, 55.8 years; 61% males). The risk of bias was assessed as 'low' for five of the seven mortality results and as 'some concerns' and 'high' in one trial each. There were 657/3100 (21.2%) and 1244/5654 (22%) deaths among patients randomized to AZM and standard of care, respectively. The use of AZM was not associated with mortality in Covid-19 patients (OR = 0.96, 95% CI 0.88-1.05, p = 0.317 based on the random-effect meta-analysis). The use of AZM was not associated with need for invasive mechanical ventilation (OR = 0.96, 95% CI 0.49-1.87, p = 0.85) and length of stay (Δ = 1.11, 95% CI -2.08 to 4.31, p = 0.49). The results show that using AZM as routine therapy in Covid-19 patients is not justified due to lack of efficacy and potential risk of bacterial resistance that is not met by an increased clinical benefit.
Topics: Anti-Bacterial Agents; Azithromycin; COVID-19; Humans; Middle Aged; Randomized Controlled Trials as Topic; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34077600
DOI: 10.1002/rmv.2258 -
Archives of Gynecology and Obstetrics Sep 2022Globally, antimicrobial resistance (AMR) restricted the armamentarium of the health care providers against infectious diseases, mainly due to the emergence of multidrug... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Globally, antimicrobial resistance (AMR) restricted the armamentarium of the health care providers against infectious diseases, mainly due to the emergence of multidrug resistant. This review is aimed at providing contemporary bacterial profile and antimicrobial resistance pattern among pregnant women with significant bacteriuria.
METHODS
Electronic biomedical databases and indexing services such as PubMed/MEDLINE, Web of Science, EMBASE and Google Scholar were searched. Original records of research articles, available online from 2008 to 2021, addressing the prevalence of significant bacteriuria and AMR pattern among pregnant women and written in English were identified and screened. The relevant data were extracted from included studies using a format prepared in Microsoft Excel and exported to STATA 14.0 software for the outcome measure analyses and subgrouping.
RESULTS
The data of 5894 urine samples from 20 included studies conducted in 8 regions of the country were pooled. The overall pooled estimate of bacteriuria was 15% (95% CI 13-17%, I = 77.94%, p < 0.001) with substantial heterogeneity. The pooled estimate of Escherichia coli recovered from isolates of 896 urine samples was 41% (95% CI 38-45%) followed by coagulase-negative Staphylococci, 22% (95% CI 18-26%), Staphylococcus aureus, 15% (95% CI 12-18%), Staphylococcus saprophytic, 12% (95% CI 6-18%) Proteus mirabilis, 7% (95% CI 4-10%), Enterococcus species, 6% (0-12%), Pseudomonas aeruginosa, 4% (2-6%), Citrobacter species, 4% (95% CI 2-4%), Group B streptococcus, 3% (1-5%), and Enterobacter species, 2% (1-4%). Multidrug resistance proportions of E. coli, Klebsiella species, Staphylococcus aureus and Coagulase negative staphylococci, 83% (95% CI 76-91%), 78% (95% CI 66-90%), 89% (95% CI 83-96%), and 78% (95% CI 67-88%), respectively.
CONCLUSION
The result of current review revealed the occurrence of substantial bacteriuria among pregnant women in Ethiopia. Resistance among common bacteria (E. coli, Klebsiella species, Staphylococci species) causing UTIs in pregnant women is widespread to commonly used antibiotics. The high rate of drug resistance in turn warrants the need for regular epidemiological surveillance of antibiotic resistance and implementation of an efficient infection control and stewardship program.
Topics: Anti-Bacterial Agents; Bacteria; Bacteriuria; Coagulase; Drug Resistance, Bacterial; Escherichia coli; Ethiopia; Female; Humans; Microbial Sensitivity Tests; Pregnancy; Pregnant Women; Staphylococcal Infections; Staphylococcus aureus
PubMed: 35032208
DOI: 10.1007/s00404-021-06365-4 -
The Journal of Antibiotics Feb 2016Despite the growing threat of antimicrobial resistance, pharmaceutical and biotechnology firms are reluctant to develop novel antibiotics because of a host of market... (Review)
Review
Despite the growing threat of antimicrobial resistance, pharmaceutical and biotechnology firms are reluctant to develop novel antibiotics because of a host of market failures. This problem is complicated by public health goals that demand antibiotic conservation and equitable patient access. Thus, an innovative incentive strategy is needed to encourage sustainable investment in antibiotics. This systematic review consolidates, classifies and critically assesses a total of 47 proposed incentives. Given the large number of possible strategies, a decision framework is presented to assist with the selection of incentives. This framework focuses on addressing market failures that result in limited investment, public health priorities regarding antibiotic stewardship and patient access, and implementation constraints and operational realities. The flexible nature of this framework allows policy makers to tailor an antibiotic incentive package that suits a country's health system structure and needs.
Topics: Anti-Bacterial Agents; Decision Support Techniques; Drug Discovery; Global Health; Health Policy; Humans; Motivation
PubMed: 26464014
DOI: 10.1038/ja.2015.98 -
PLoS Medicine Jun 2023Bloodstream infections (BSIs) produced by antibiotic-resistant bacteria (ARB) cause a substantial disease burden worldwide. However, most estimates come from high-income... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bloodstream infections (BSIs) produced by antibiotic-resistant bacteria (ARB) cause a substantial disease burden worldwide. However, most estimates come from high-income settings and thus are not globally representative. This study quantifies the excess mortality, length of hospital stay (LOS), intensive care unit (ICU) admission, and economic costs associated with ARB BSIs, compared to antibiotic-sensitive bacteria (ASB), among adult inpatients in low- and middle-income countries (LMICs).
METHODS AND FINDINGS
We conducted a systematic review by searching 4 medical databases (PubMed, SCIELO, Scopus, and WHO's Global Index Medicus; initial search n = 13,012 from their inception to August 1, 2022). We only included quantitative studies. Our final sample consisted of n = 109 articles, excluding studies from high-income countries, without our outcomes of interest, or without a clear source of bloodstream infection. Crude mortality, ICU admission, and LOS were meta-analysed using the inverse variance heterogeneity model for the general and subgroup analyses including bacterial Gram type, family, and resistance type. For economic costs, direct medical costs per bed-day were sourced from WHO-CHOICE. Mortality costs were estimated based on productivity loss from years of potential life lost due to premature mortality. All costs were in 2020 USD. We assessed studies' quality and risk of publication bias using the MASTER framework. Multivariable meta-regressions were employed for the mortality and ICU admission outcomes only. Most included studies showed a significant increase in crude mortality (odds ratio (OR) 1.58, 95% CI [1.35 to 1.80], p < 0.001), total LOS (standardised mean difference "SMD" 0.49, 95% CI [0.20 to 0.78], p < 0.001), and ICU admission (OR 1.96, 95% CI [1.56 to 2.47], p < 0.001) for ARB versus ASB BSIs. Studies analysing Enterobacteriaceae, Acinetobacter baumanii, and Staphylococcus aureus in upper-middle-income countries from the African and Western Pacific regions showed the highest excess mortality, LOS, and ICU admission for ARB versus ASB BSIs per patient. Multivariable meta-regressions indicated that patients with resistant Acinetobacter baumanii BSIs had higher mortality odds when comparing ARB versus ASB BSI patients (OR 1.67, 95% CI [1.18 to 2.36], p 0.004). Excess direct medical costs were estimated at $12,442 (95% CI [$6,693 to $18,191]) for ARB versus ASB BSI per patient, with an average cost of $41,103 (95% CI [$30,931 to $51,274]) due to premature mortality. Limitations included the poor quality of some of the reviewed studies regarding the high risk of selective sampling or failure to adequately account for relevant confounders.
CONCLUSIONS
We provide an overview of the impact ARB BSIs in limited resource settings derived from the existing literature. Drug resistance was associated with a substantial disease and economic burden in LMICs. Although, our results show wide heterogeneity between WHO regions, income groups, and pathogen-drug combinations. Overall, there is a paucity of BSI data from LMICs, which hinders implementation of country-specific policies and tracking of health progress.
Topics: Adult; Humans; Developing Countries; Inpatients; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Sepsis; Bacteria; Anti-Bacterial Agents
PubMed: 37347726
DOI: 10.1371/journal.pmed.1004199 -
Systematic Reviews Jul 2021Ocular toxoplasmosis (OT) is the most common cause of posterior uveitis, which leads to visual impairment in a large proportion of patients. Antibiotics and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ocular toxoplasmosis (OT) is the most common cause of posterior uveitis, which leads to visual impairment in a large proportion of patients. Antibiotics and corticosteroids lower the risk of permanent visual loss by controlling infection and inflammation. However, there remains disagreement regarding optimal antibiotic therapy for OT. Therefore, this systematic review and meta-analysis were performed to determine the effects and safety of existing antibiotic treatment regimens for OT.
METHODS
MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials, LILACS, WHO International Clinical Trials Registry Platform portal, ClinicalTrials.gov, and Gray Literature in Europe ("OpenGrey") were searched for relevant studies; manual searches of reference lists were performed for studies identified by other methods. All published and unpublished randomized controlled trials that compared antibiotic schemes known to be effective in OT at any dosage, duration, and administration route were included. Studies comparing antibiotics with placebo were excluded. This review followed standard methodological procedures recommended by the Cochrane group.
RESULTS
Ten studies were included in the narrative summary, of which four were included for quantitative synthesis (meta-analysis). Interventions were organized into three groups: intravitreal clindamycin versus pyrimethamine + sulfadiazine, trimethoprim + sulfamethoxazole versus other antibiotics, and other interventions. The first comparison favored intravitreal clindamycin (Mean difference (MD) = 0.10 logMAR; 95% confidence interval = 0.01 to 0.22). However, this finding lacks clinical relevance. Other outcomes showed no statistically significant differences between the treatment groups. In general, the risk of performance bias was high in evaluated studies, and the quality of the evidence found was low to very low.
CONCLUSIONS
No antibiotic scheme was superior to others, and the selection of a treatment regimen depends on multiple factors; therefore, treatment should be chosen based on safety, sulfa allergies, and availability.
Topics: Anti-Bacterial Agents; Clindamycin; Europe; Humans; Toxoplasmosis, Ocular
PubMed: 34275483
DOI: 10.1186/s13643-021-01758-7