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Thorax Oct 2021The main aim of this network meta-analysis is to identify the empiric antibiotic (Em-ATB) with the highest probability of being the best (HPBB) in terms of (1) cure rate... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The main aim of this network meta-analysis is to identify the empiric antibiotic (Em-ATB) with the highest probability of being the best (HPBB) in terms of (1) cure rate and (2) mortality rate in hospitalised patients with community acquired pneumonia (CAP) .
METHOD
Inclusion criteria: (1) adult patients (>16 years old) diagnosed with CAP that required hospitalisation; (2) randomised to at least two different Em-ATBs, (3) that report cure rate and (4) are written in English or Spanish.
EXCLUSION CRITERIA
(1) ambiguous antibiotics protocol and (2) published exclusively in abstract or letter format.
DATA SOURCES
Medline, Embase, Cochrane and citation reviews from 1 January 2000 to 31 December 2018. Risk of bias: Cochrane's tool. Quality of the systematic review (SR): A MeaSurement Tool to Assess systematic Reviews-2. Certainity of the evidence: Grading of Recommendations Assessment, Development and Evaluation.
STATISTICAL ANALYSES
frequentist method performed with the 'netmeta' library, R package.
RESULTS
27 randomised controlled trials (RCTs) from the initial 41 307 screened citations were included. Regarding the risk of bias, more than one quarter of the studies presented low risk and no study presented high risk in all domains. The SR quality is moderate. two networks were constructed. Thus, two Em-ATBs have the HPBB: cetaroline 600 mg (two times a day) and piperacillin 2000 mg (two times a day). three networks were constructed. Thus, three Em-ATBs have the HPBB: ceftriaxone 2000 mg (once a day) plus levofloxacin 500 (two times a day), ertapenem 1000 mg (two times a day) and amikacin 250 mg (two times a day) plus clarithromycin 500 mg (two times a day). The certainity of evidence for each results is moderate.
CONCLUSION
For cure rate, ceftaroline and piperaciline are the options with the HPBB. However, for mortality rate, the options are ceftriaxone plus levofloxacin, ertapenem and amikacin plus clarithromycin. It seems necessary to conduct an RCT that compares treatments with the HPBB for each event (cure or mortality) (CRD42017060692).
Topics: Adolescent; Adult; Anti-Bacterial Agents; Community-Acquired Infections; Humans; Network Meta-Analysis; Pneumonia
PubMed: 33723019
DOI: 10.1136/thoraxjnl-2019-214054 -
Medicine Feb 2021Meropenem monotherapy vs ceftazidime plus amikacin have been approved for use against febrile neutropenia. To assess the effectiveness and safety of them for empirical... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Meropenem monotherapy vs ceftazidime plus amikacin have been approved for use against febrile neutropenia. To assess the effectiveness and safety of them for empirical treatment of cancer patients with febrile neutropenia, we conducted a meta-analysis of randomized controlled trial.
METHODS
Randomized controlled trials on ceftazidime plus amikacin, or/and monotherapy with meropenem for the treatment of cancer patients with febrile neutropenia were identified by searching Cochrane Library, PubMed, Science Direct, Wiley Online, Science Citation Index, Google (scholar), National Center for Biotechnology Information, and China National Knowledge Infrastructure. Data on interventions, participants' characteristics and the outcomes of therapy, were extracted for statistical analysis. Seven trials fulfilled the inclusion criteria.
RESULT
The treatment with ceftazidime plus amikacin was more effective than meropenem (OR = 1.17; 95% CI 0.93-1.46; 1270 participants). However, the treatment effects of the 2 therapy methods were almost parallel in adults (OR = 1.15; 95% CI 0.91-1.46; 1130 participants older than 16). Drug-related adverse effects afflicted more patients treated with ceftazidime plus amikacin (OR = 0.78; 95% CI 0.52-1.15; 1445 participants). The common responses were nausea, diarrhea, rash, and increased in serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase and bilirubin.
CONCLUSION
Ceftazidime plus amikacin should be the first choice for empirical treatment of cancer patients with febrile neutropenia, and meropenem may be chosen as a last defense against pathogenic bacteria.
Topics: Amikacin; Anti-Bacterial Agents; Ceftazidime; Drug Therapy, Combination; Febrile Neutropenia; Humans; Meropenem; Neoplasms
PubMed: 33663117
DOI: 10.1097/MD.0000000000024883 -
Clinical Microbiology and Infection :... Apr 2021Nocardiosis is a rare infection that is often difficult to treat and may be life-threatening. There is no consensus on its management.
BACKGROUND
Nocardiosis is a rare infection that is often difficult to treat and may be life-threatening. There is no consensus on its management.
OBJECTIVES
Our aim was to provide the current evidence for the diagnosis and management of individuals with nocardiosis, and to propose a management approach for this uncommon infection.
SOURCES
We systematically searched the medical literature on nocardiosis for studies published between 2010 and 2020 and describing ten or more individuals.
CONTENT
Nocardiosis, a primarily opportunistic infection which may occur in immunocompetent persons, most commonly involves the lungs and frequently disseminates to other sites including the central nervous system. The reference standard for Nocardia species identification is molecular biology, and the preferred method for antibiotic susceptibility testing (AST) is broth microdilution. Monotherapy seems appropriate for patients with primary skin nocardiosis or non-severe pulmonary disease; we reserve a multidrug regimen for more severe infections. Species identification and AST results are often missing at initiation of antibiotics. Trimethoprim-sulfamethoxazole is the preferred agent for initial therapy, because Nocardia is very often susceptible to this agent, and because it has been the keystone of nocardiosis treatment for years. Linezolid, to which Nocardia is almost always susceptible, may be an alternative. When combination therapy is required, the repertoire of companion drugs includes third-generation cephalosporins, amikacin and imipenem. Therapeutic modifications should take into account clinical response to initial therapy and AST results. Treatment duration of 6 months is appropriate for most situations, but longer durations are preferred for disseminated nocardiosis and shorter durations are reasonable in low-risk situations. Secondary prophylaxis may be considered in selected individuals with permanent immunosuppression.
IMPLICATIONS
We hereby provide the clinician with an easy-to-use algorithm for the management of individuals with nocardiosis. We also illuminate gaps in evidence and suggest future research directions.
Topics: Algorithms; Anti-Bacterial Agents; Humans; Nocardia; Nocardia Infections
PubMed: 33418019
DOI: 10.1016/j.cmi.2020.12.019 -
The International Journal of... Jan 2021The use of injectable antibiotics to treat multidrug-resistant TB (MDR-TB) is associated with substantial morbidity due to long-term hearing loss. This systematic... (Meta-Analysis)
Meta-Analysis
The use of injectable antibiotics to treat multidrug-resistant TB (MDR-TB) is associated with substantial morbidity due to long-term hearing loss. This systematic review evaluates the incidence of ototoxicity among patients treated for MDR-TB, and the evidence for routine audiometric monitoring to mitigate its severity. Studies of ototoxicity among patients with MDR-TB were identified from six databases: PubMed, MEDLINE, Web of Science, Embase, SCOPUS and the Cochrane Library. Meta-analyses were performed to determine the overall incidence of hearing loss, tinnitus and vertigo. The incidence of hearing loss was further stratified by country income status and the injectable agent used during treatment. Among 64 studies from 25 countries including 12 793 patients, 28.3% (95%CI 23.4-33.1) of patients treated with injectables reported hearing loss. Tinnitus and vertigo were experienced by respectively 14.5% (95%CI 10.3-18.7) and 8.1% (95%CI 4.7-11.6) of patients. The incidence of hearing loss was highest among patients treated with amikacin (33.4%, 95%CI 18.2-48.6), and lowest among those treated with capreomycin (2.0%, 95%CI 0-5.5). We found that audiometry was widely used as a method of evaluating hearing loss, and was feasible in a wide range of settings. Injectable antibiotics contribute to significant morbidity in patients with MDR-TB. In settings where they are used, routine audiometric monitoring is recommended to prevent irreversible damage.
Topics: Amikacin; Antitubercular Agents; Capreomycin; Humans; Ototoxicity; Tuberculosis, Multidrug-Resistant
PubMed: 33384041
DOI: 10.5588/ijtld.20.0217 -
Current Drug Metabolism 2021Many antibiotics have a high potential for interactions with drugs, as a perpetrator and/or victim, in critically ill patients, and particularly in sepsis patients.
BACKGROUND
Many antibiotics have a high potential for interactions with drugs, as a perpetrator and/or victim, in critically ill patients, and particularly in sepsis patients.
METHODS
The aim of this review is to summarize the pharmacokinetic drug-drug interaction (DDI) of 45 antibiotics commonly used in sepsis care in China. Literature search was conducted to obtain human pharmacokinetics/ dispositions of the antibiotics, their interactions with drug-metabolizing enzymes or transporters, and their associated clinical drug interactions. Potential DDI is indicated by a DDI index ≥ 0.1 for inhibition or a treatedcell/ untreated-cell ratio of enzyme activity being ≥ 2 for induction.
RESULTS
The literature-mined information on human pharmacokinetics of the identified antibiotics and their potential drug interactions is summarized.
CONCLUSION
Antibiotic-perpetrated drug interactions, involving P450 enzyme inhibition, have been reported for four lipophilic antibacterials (ciprofloxacin, erythromycin, trimethoprim, and trimethoprim-sulfamethoxazole) and three antifungals (fluconazole, itraconazole, and voriconazole). In addition, seven hydrophilic antibacterials (ceftriaxone, cefamandole, piperacillin, penicillin G, amikacin, metronidazole, and linezolid) inhibit drug transporters in vitro. Despite no clinical PK drug interactions with the transporters, caution is advised in the use of these antibacterials. Eight hydrophilic antibiotics (all β-lactams; meropenem, cefotaxime, cefazolin, piperacillin, ticarcillin, penicillin G, ampicillin, and flucloxacillin), are potential victims of drug interactions due to transporter inhibition. Rifampin is reported to perpetrate drug interactions by inducing CYP3A or inhibiting OATP1B; it is also reported to be a victim of drug interactions, due to the dual inhibition of CYP3A4 and OATP1B by indinavir. In addition, three antifungals (caspofungin, itraconazole, and voriconazole) are reported to be victims of drug interactions because of P450 enzyme induction. Reports for other antibiotics acting as victims in drug interactions are scarce.
Topics: Anti-Bacterial Agents; Antifungal Agents; China; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme System; Drug Interactions; Humans; Rifampin; Sepsis
PubMed: 32990533
DOI: 10.2174/1389200221666200929115117 -
Frontiers in Public Health 2020China is a high-burden country of tuberculosis. The proportion of diseases caused by non-tuberculous mycobacteria (NTM) has increased, seriously affecting the... (Meta-Analysis)
Meta-Analysis
China is a high-burden country of tuberculosis. The proportion of diseases caused by non-tuberculous mycobacteria (NTM) has increased, seriously affecting the prevention, control, and management of tuberculosis (TB) and posing a significant threat to human health. However, there is a lack of an organized monitoring system for NTM such as that used for tuberculosis. Comprehensive data on patient susceptibility, dominant species, and drug resistance profiles are needed to improve the treatment protocols and the management of NTM. Primary research reports of NTM clinical specimens from mainland China published between January 1, 2000 and May 31, 2019 were retrieved from four online resources (BIOSIS, Embase, PubMed, and Web of Science) and three Chinese medical literature databases (CNKI, Wanfang, and Vip) as the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. In total, 339 publications were included in the systematic review, 129 were used in the drug susceptibility analysis, and 95 were used in the meta-analysis. Traditional culture using Lowenstein-Jensen slants combined with P-nitrobenzene acid and thiophene-2-carboxylic acid hydrazine differential medium and proportional method was most commonly used for the isolation, identification, and drug susceptibility testing of NTM in China. The crude isolation rate for NTM among TB suspected cases was 4.66-5.78%, while the proportion of NTM among isolates was 11.57%. and complex were the most common clinical NTM species. NTM only showed general sensitivity to ethambutol, linezolid, clofazimine, amikacin, tobramycin, and clarithromycin. The prevalence of NTM in China has shown a decreasing trend. was replaced as the dominant species by over the course of the study. The geographic diversity of different species showed the effects of environmental and economic factors on the distribution of NTM and indicated that there were important factors still not identified. While there were only a limited number of antibiotics to which NTM showed any sensitivity, the drug resistance profiles of the isolates were highly variable and thus more caution should be taken when empirically treating NTM infection.
Topics: China; Drug Resistance, Microbial; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Nontuberculous Mycobacteria; Prevalence
PubMed: 32850570
DOI: 10.3389/fpubh.2020.00295 -
Clinical Infectious Diseases : An... May 2020The safety profile of antimicrobials used during pregnancy is one important consideration in the decision on how to treat and provide postexposure prophylaxis (PEP) for...
BACKGROUND
The safety profile of antimicrobials used during pregnancy is one important consideration in the decision on how to treat and provide postexposure prophylaxis (PEP) for plague during pregnancy.
METHODS
We searched 5 scientific literature databases for primary sources on the safety of 9 antimicrobials considered for plague during pregnancy (amikacin, gentamicin, plazomicin, streptomycin, tobramycin, chloramphenicol, doxycycline, sulfadiazine, and trimethoprim-sulfamethoxazole [TMP-SMX]) and abstracted data on maternal, pregnancy, and fetal/neonatal outcomes.
RESULTS
Of 13 052 articles identified, 66 studies (case-control, case series, cohort, and randomized studies) and 96 case reports were included, totaling 27 751 prenatal exposures to amikacin (n = 9), gentamicin (n = 345), plazomicin (n = 0), streptomycin (n = 285), tobramycin (n = 43), chloramphenicol (n = 246), doxycycline (n = 2351), sulfadiazine (n = 870), and TMP-SMX (n = 23 602). Hearing or vestibular deficits were reported in 18/121 (15%) children and 17/109 (16%) pregnant women following prenatal streptomycin exposure. First trimester chloramphenicol exposure was associated with an elevated risk of an undescended testis (odds ratio [OR] 5.9, 95% confidence interval [CI] 1.2-28.7). Doxycycline was associated with cardiovascular malformations (OR 2.4, 95% CI 1.2-4.7) in 1 study and spontaneous abortion (OR 2.8, 95% CI 1.9-4.1) in a separate study. First trimester exposure to TMP-SMX was associated with increased risk of neural tube defects (pooled OR 2.5, 95% CI 1.4-4.3), spontaneous abortion (OR 3.5, 95% CI 2.3-5.6), preterm birth (OR 1.5, 95% CI 1.1-2.1), and small for gestational age (OR 1.6, 95% CI 1.2-2.2). No other statistically significant associations were reported.
CONCLUSIONS
For most antimicrobials reviewed, adverse maternal/fetal/neonatal outcomes were not observed consistently. Prenatal exposure to streptomycin and TMP-SMX was associated with select birth defects in some studies. Based on limited data, chloramphenicol and doxycycline may be associated with adverse pregnancy or neonatal outcomes; however, more data are needed to confirm these associations. Antimicrobials should be used for treatment and PEP of plague during pregnancy; the choice of antimicrobials may be influenced by these data as well as information about the risks of plague during pregnancy.
Topics: Abortion, Spontaneous; Anti-Infective Agents; Child; Female; Humans; Infant, Newborn; Male; Plague; Pregnancy; Premature Birth; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 32435799
DOI: 10.1093/cid/ciz1231 -
The Lancet. Respiratory Medicine Apr 2020Treatment of multidrug-resistant tuberculosis requires long-term therapy with a combination of multiple second-line drugs. These drugs are associated with numerous... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Treatment of multidrug-resistant tuberculosis requires long-term therapy with a combination of multiple second-line drugs. These drugs are associated with numerous adverse events that can cause severe morbidity, such as deafness, and in some instances can lead to death. Our aim was to estimate the absolute and relative frequency of adverse events associated with different tuberculosis drugs to provide useful information for clinicians and tuberculosis programmes in selecting optimal treatment regimens.
METHODS
We did a meta-analysis using individual-level patient data that were obtained from studies that reported adverse events that resulted in permanent discontinuation of anti-tuberculosis medications. We used a database created for our previous meta-analysis of multidrug-resistant tuberculosis treatment and outcomes, for which we did a systematic review of literature published between Jan 1, 2009, and Aug 31, 2015 (updated April 15, 2016), and requested individual patient-level information from authors. We also considered for this analysis studies contributing patient-level data in response to a public call made by WHO in 2018. Meta-analysis for proportions and arm-based network meta-analysis were done to estimate the incidence of adverse events for each tuberculosis drug.
FINDINGS
58 studies were identified, including 50 studies from the updated individual patient data meta-analysis for multidrug-resistant tuberculosis treatment. 35 of these studies, with 9178 patients, were included in our analysis. Using meta-analysis of proportions, drugs with low risks of adverse event occurrence leading to permanent discontinuation included levofloxacin (1·3% [95% CI 0·3-5·0]), moxifloxacin (2·9% [1·6-5·0]), bedaquiline (1·7% [0·7-4·2]), and clofazimine (1·6% [0·5-5·3]). Relatively high incidence of adverse events leading to permanent discontinuation was seen with three second-line injectable drugs (amikacin: 10·2% [6·3-16·0]; kanamycin: 7·5% [4·6-11·9]; capreomycin: 8·2% [6·3-10·7]), aminosalicylic acid (11·6% [7·1-18·3]), and linezolid (14·1% [9·9-19·6]). Risk of bias in selection of studies was judged to be low because there were no important differences between included and excluded studies. Variability between studies was significant for most outcomes analysed.
INTERPRETATION
Fluoroquinolones, clofazimine, and bedaquiline had the lowest incidence of adverse events leading to permanent drug discontinuation, whereas second-line injectable drugs, aminosalicylic acid, and linezolid had the highest incidence. These results suggest that close monitoring of adverse events is important for patients being treated for multidrug-resistant tuberculosis. Our results also underscore the urgent need for safer and better-tolerated drugs to reduce morbidity from treatment itself for patients with multidrug-resistant tuberculosis.
FUNDING
Canadian Institutes of Health Research, Centers for Disease Control and Prevention (USA), American Thoracic Society, European Respiratory Society, and Infectious Diseases Society of America.
Topics: Adult; Aminosalicylic Acid; Antitubercular Agents; Canada; Clofazimine; Diarylquinolines; Drug-Related Side Effects and Adverse Reactions; Female; Fluoroquinolones; Humans; Incidence; Linezolid; Male; Mycobacterium tuberculosis; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary
PubMed: 32192585
DOI: 10.1016/S2213-2600(20)30047-3 -
International Journal of Preventive... 2019Urinary tract infection (UTI) is one of the most common infectious diseases ranking next to upper respiratory tract infections. UTIs are often significantly associated... (Review)
Review
BACKGROUND
Urinary tract infection (UTI) is one of the most common infectious diseases ranking next to upper respiratory tract infections. UTIs are often significantly associated with morbidity and mortality. The inappropriate administration of antibiotics to treat these infections increased infection resistance to antibiotics. The aim of this study is to determine the frequency of antibiotic resistance pattern in UTIs.
METHODS
We searched several databases including PubMed, Web of Science, Scopus, Google Scholar, Iran Medex, Magiran, IranDoc, MedLib, and Scientific Information Database to identify the studies addressing antibacterial resistance patterns of the most common uropathogenic bacteria in UTIs in Iran. A total of 90 reports published from different regions of Iran from 1992 to May 2015 were involved in this study.
RESULTS
It is shown that the most common pathogen causing UTIs is with 62%. The resistance among the isolates of was as follows: ampicillin (86%), amoxicillin (76%), tetracycline (71%), trimethoprim-sulfamethoxazole (64%), cephalexin (61%), and cefalothin (60%). The highest sensitivity among isolates of was as follows: imipenem (86%), nitrofurantoin (82%), amikacin (79%), chloramphenicol (72%), and ciprofloxacin (72%).
CONCLUSIONS
The results of this study showed that the most common resistance are antibiotics that are commonly used. The most effective antibiotics for were imipenem, nitrofurantoin, amikacin, chloramphenicol, and ciprofloxacin. Considering this study, it had better, use less gentamicin, second-generation cephalosporins, and nalidixic acid in the initial treatment of infections caused by , and no use penicillins, tetracyclines, cotrimoxazole, and first-generation cephalosporins.
PubMed: 32133087
DOI: 10.4103/ijpvm.IJPVM_419_17 -
Antimicrobial Resistance and Infection... 2019Despite a high mortality rate in childhood, there is limited evidence on the causes and outcomes of paediatric bloodstream infections from low- and middle-income... (Meta-Analysis)
Meta-Analysis
Bacterial pathogens and resistance causing community acquired paediatric bloodstream infections in low- and middle-income countries: a systematic review and meta-analysis.
BACKGROUND
Despite a high mortality rate in childhood, there is limited evidence on the causes and outcomes of paediatric bloodstream infections from low- and middle-income countries (LMICs). We conducted a systematic review and meta-analysis to characterize the bacterial causes of paediatric bloodstream infections in LMICs and their resistance profile.
METHODS
We searched Pubmed and Embase databases between January 1st 1990 and October 30th 2019, combining MeSH and free-text terms for "sepsis" and "low-middle-income countries" in children. Two reviewers screened articles and performed data extraction to identify studies investigating children (1 month-18 years), with at least one blood culture. The main outcomes of interests were the rate of positive blood cultures, the distribution of bacterial pathogens, the resistance patterns and the case-fatality rate. The proportions obtained from each study were pooled using the Freeman-Tukey double arcsine transformation, and a random-effect meta-analysis model was used.
RESULTS
We identified 2403 eligible studies, 17 were included in the final review including 52,915 children (11 in Africa and 6 in Asia). The overall percentage of positive blood culture was 19.1% [95% CI: 12.0-27.5%]; 15.5% [8.4-24.4%] in Africa and 28.0% [13.2-45.8%] in Asia. A total of 4836 bacterial isolates were included in the studies; 2974 were Gram-negative (63.9% [52.2-74.9]) and 1858 were Gram-positive (35.8% [24.9-47.5]). In Asia, typhi (26.2%) was the most commonly isolated pathogen, followed by (7.7%) whereas in Africa, (17.8%) and (16.8%) were predominant followed by (10.7%). was more likely resistant to methicillin in Africa (29.5% vs. 7.9%), whereas was more frequently resistant to third-generation cephalosporins (31.2% vs. 21.2%), amikacin (29.6% vs. 0%) and ciprofloxacin (36.7% vs. 0%) in Asia. The overall estimate for case-fatality rate among 8 studies was 12.7% [6.6-20.2%]. Underlying conditions, such as malnutrition or HIV infection were assessed as a factor associated with bacteraemia in 4 studies each.
CONCLUSIONS
We observed a marked variation in pathogen distribution and their resistance profiles between Asia and Africa. Very limited data is available on underlying risk factors for bacteraemia, patterns of treatment of multidrug-resistant infections and predictors of adverse outcomes.
Topics: Adolescent; Africa; Anti-Bacterial Agents; Asia; Bacteremia; Bacteria; Child; Child Health; Child, Preschool; Community-Acquired Infections; Developing Countries; Drug Resistance, Bacterial; Humans; Infant; Microbial Sensitivity Tests; Observational Studies as Topic; Poverty; Sepsis
PubMed: 31893041
DOI: 10.1186/s13756-019-0673-5