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Clinical Reviews in Allergy & Immunology Apr 2024Secondary prevention with penicillin aims to prevent further episodes of acute rheumatic fever and subsequent development of rheumatic heart disease (RHD). Penicillin... (Meta-Analysis)
Meta-Analysis Review
Secondary prevention with penicillin aims to prevent further episodes of acute rheumatic fever and subsequent development of rheumatic heart disease (RHD). Penicillin allergy, self-reported by 10% of the population, can affect secondary prevention programs. We aimed to assess the role for (i) routine penicillin allergy testing and the (ii) safety of penicillin allergy delabeling approaches in this context. We searched MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, WHO ICTRP, ISRCTN, and CPCI-S to identify the relevant reports. We found 2419 records, but no studies addressed our initial question. Following advice from the WHO-Guideline committee and experts, we identified 6 manuscripts on allergy testing focusing on other populations showing that the prevalence of allergy confirmed by testing was low and the incidence of life-threatening reactions to BPG was very low (< 1-3/1000 individuals treated). A subsequent search addressed penicillin allergy delabeling. This found 516 records, and 5 studies addressing the safety of direct oral drug challenge vs. skin testing followed by drug administration in patients with suspected penicillin allergy. Immediate allergic reactions of minor severity were observed for a minority of patients and occurred less frequently in the direct drug challenge group: 2.3% vs. 11.5%; RR = 0.25, 95%CI 0.15-0.45, P < 0.00001, I = 0%. No anaphylaxis or deaths were observed. Severe allergic reactions to penicillin are extremely rare and can be recognized and dealt by trained healthcare workers. Confirmation of penicillin allergy diagnosis or delabeling using direct oral drug challenge or penicillin skin testing seems to be safe and is associated with a low rate of adverse reactions.
Topics: Humans; Drug Hypersensitivity; Penicillins; Skin Tests; Practice Guidelines as Topic; World Health Organization; Anti-Bacterial Agents
PubMed: 38696031
DOI: 10.1007/s12016-024-08988-2 -
The Cochrane Database of Systematic... Nov 2023Antibiotics provide only modest benefit in treating sore throat, although their effectiveness increases in people with positive throat swabs for group A beta-haemolytic... (Review)
Review
BACKGROUND
Antibiotics provide only modest benefit in treating sore throat, although their effectiveness increases in people with positive throat swabs for group A beta-haemolytic streptococci (GABHS). It is unclear which antibiotic is the best choice if antibiotics are indicated. This is an update of a review first published in 2010, and updated in 2013, 2016, and 2021.
OBJECTIVES
To assess the comparative efficacy of different antibiotics in: (a) alleviating symptoms (pain, fever); (b) shortening the duration of the illness; (c) preventing clinical relapse (i.e. recurrence of symptoms after initial resolution); and (d) preventing complications (suppurative complications, acute rheumatic fever, post-streptococcal glomerulonephritis). To assess the evidence on the comparative incidence of adverse effects and the risk-benefit of antibiotic treatment for streptococcal pharyngitis.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2023, Issue 2), MEDLINE Ovid, Embase Elsevier, and Web of Science (Clarivate) up to 19 March 2023.
SELECTION CRITERIA
Randomised, double-blind trials comparing different antibiotics, and reporting at least one of the following: clinical cure, clinical relapse, or complications and/or adverse events.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened trials for inclusion and extracted data using standard methodological procedures recommended by Cochrane. We assessed the risk of bias in the included studies according to the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions, and used the GRADE approach to assess the overall certainty of the evidence for the outcomes. We reported the intention-to-treat analysis, and also performed an analysis of evaluable participants to explore the robustness of the intention-to-treat results.
MAIN RESULTS
We included 19 trials reported in 18 publications (5839 randomised participants): six trials compared penicillin with cephalosporins; six compared penicillin with macrolides; three compared penicillin with carbacephem; one compared penicillin with sulphonamides; one compared clindamycin with ampicillin; and one compared azithromycin with amoxicillin in children. All participants had confirmed acute GABHS tonsillopharyngitis, and ages ranged from one month to 80 years. Nine trials included only, or predominantly, children. Most trials were conducted in an outpatient setting. Reporting of randomisation, allocation concealment, and blinding was poor in all trials. We downgraded the certainty of the evidence mainly due to lack of (or poor reporting of) randomisation or blinding, or both, heterogeneity, and wide confidence intervals. Cephalosporins versus penicillin We are uncertain if there is a difference in symptom resolution (at 2 to 15 days) for cephalosporins versus penicillin (odds ratio (OR) for absence of symptom resolution 0.79, 95% confidence interval (CI) 0.55 to 1.12; 5 trials, 2018 participants; low-certainty evidence). Results of the sensitivity analysis of evaluable participants differed (OR 0.51, 95% CI 0.27 to 0.97; 5 trials, 1660 participants; very low-certainty evidence). Based on an analysis of evaluable participants, we are uncertain if clinical relapse may be lower for cephalosporins compared with penicillin (OR 0.55, 95% CI 0.30 to 0.99; number needed to treat for an additional beneficial outcome (NNTB) 50; 4 trials, 1386 participants; low-certainty evidence). Very low-certainty evidence showed no difference in reported adverse events. Macrolides versus penicillin We are uncertain if there is a difference between macrolides and penicillin for resolution of symptoms (OR 1.11, 95% CI 0.92 to 1.35; 6 trials, 1728 participants; low-certainty evidence). Sensitivity analysis of evaluable participants resulted in an OR of 0.79 (95% CI 0.57 to 1.09; 6 trials, 1159 participants). We are uncertain if clinical relapse may be different (OR 1.21, 95% CI 0.48 to 3.03; 6 trials, 802 participants; low-certainty evidence). Children treated with macrolides seemed to experience more adverse events than those treated with penicillin (OR 2.33, 95% CI 1.06 to 5.15; 1 trial, 489 participants; low-certainty evidence). However, the test for subgroup differences between children and adults was not significant. Azithromycin versus amoxicillin Based on one unpublished trial in children, we are uncertain if resolution of symptoms is better with azithromycin in a single dose versus amoxicillin for 10 days (OR 0.76, 95% CI 0.55 to 1.05; 1 trial, 673 participants; very low-certainty evidence). Sensitivity analysis for per-protocol analysis resulted in an OR of 0.29 (95% CI 0.11 to 0.73; 1 trial, 482 participants; very low-certainty evidence). We are also uncertain if there was a difference in relapse between groups (OR 0.88, 95% CI 0.43 to 1.82; 1 trial, 422 participants; very low-certainty evidence). Adverse events were more common with azithromycin compared to amoxicillin (OR 2.67, 95% CI 1.78 to 3.99; 1 trial, 673 participants; very low-certainty evidence). Carbacephem versus penicillin There is low-certainty evidence that compared with penicillin, carbacephem may provide better symptom resolution post-treatment in adults and children (OR 0.70, 95% CI 0.49 to 0.99; NNTB 14.3; 3 trials, 795 participants). Studies did not report on long-term complications, so it was unclear if any class of antibiotics was better at preventing serious but rare complications.
AUTHORS' CONCLUSIONS
We are uncertain if there are clinically relevant differences in symptom resolution when comparing cephalosporins and macrolides with penicillin in the treatment of GABHS tonsillopharyngitis. Low-certainty evidence in children suggests that carbacephem may be more effective than penicillin for symptom resolution. There is insufficient evidence to draw conclusions regarding the other comparisons in this review. Data on complications were too scarce to draw conclusions. Antibiotics have a limited effect in the treatment of GABHS pharyngitis and the results do not demonstrate that other antibiotics are more effective than penicillin. In the context of antimicrobial stewardship, penicillin can be used if treatment with an antibiotic is indicated. All studies were conducted in high-income countries with a low risk of streptococcal complications, so there is a need for trials in low-income countries and disadvantaged populations, where the risk of complications remains high.
Topics: Adult; Child; Humans; Infant; Amoxicillin; Anti-Bacterial Agents; Azithromycin; Cephalosporins; Chronic Disease; Macrolides; Penicillins; Pharyngitis; Randomized Controlled Trials as Topic; Recurrence; Streptococcus pyogenes; Systematic Reviews as Topic
PubMed: 37965935
DOI: 10.1002/14651858.CD004406.pub6 -
International Journal of Pediatric... Jul 2021Arcanobacterium haemolyticum causes pharyngotonsillitis in children and young adults. It is rarely isolated in pharyngeal swabs as testing for it is not routine. Data on... (Review)
Review
INTRODUCTION
Arcanobacterium haemolyticum causes pharyngotonsillitis in children and young adults. It is rarely isolated in pharyngeal swabs as testing for it is not routine. Data on complications, management, and antibiotic susceptibility testing is limited. We sought to review the available literature on the presentation and management of A. haemolyticum pharyngotonsillitis in this age group.
METHODS
A systematic review of eligible studies reporting pharyngotonsillitis and related complications in children and young adults caused by A. haemolyticum was conducted. Literature from case reports, case series, and available cohorts was compiled. Data were analyzed using descriptive statistics.
RESULTS
The initial database search yielded 63 articles, after applying exclusion criteria 17 studies were included. 191 patients were identified with a median age of 16.5 years. The most common presentation was throat pain reported in 93.7% of patients. Tonsillar exudates, fever at presentation and rash were present in more than half of the reviewed cases. The diagnosis was established by a positive culture on a pharyngeal swab in 98.8% of swabs collected. Complications described included peritonsillar abscesses, Lemierre's syndrome, pneumonia, and sepsis. Penicillin was the first line antibiotic in 81% of patients followed by macrolides in 19 patients (18%).
CONCLUSIONS
A. haemolyticum occurs in children and young adults and may result in complications. Our review supports its susceptibility to penicillin. We suggest a diagnostic and management algorithm to guide clinicians in targeted testing and aid with decision making regarding timely and appropriate antibiotic therapy, in an effort to reduce the burden of its complications.
Topics: Actinomycetales Infections; Adolescent; Algorithms; Arcanobacterium; Child; Humans; Pharyngitis; Young Adult
PubMed: 34038812
DOI: 10.1016/j.ijporl.2021.110759 -
International Journal of Infectious... Apr 2023Penicillin allergy records are often incorrect and may result in harm. We aimed to systematically review the effectiveness and safety of nonallergist health care worker... (Meta-Analysis)
Meta-Analysis Review
The effectiveness of interventions that support penicillin allergy assessment and delabeling of adult and pediatric patients by nonallergy specialists: a systematic review and meta-analysis.
OBJECTIVES
Penicillin allergy records are often incorrect and may result in harm. We aimed to systematically review the effectiveness and safety of nonallergist health care worker delivery of penicillin allergy delabeling.
METHODS
We searched EMBASE/MEDLINE/CINAHL (Ovid), PsycInfo, Web of Science, and Cochrane CENTRAL from inception to January 21, 2022 and unpublished studies and gray literature. The proportion of patients allergic to penicillin delabeled and harmed was calculated using random-effects models.
RESULTS
Overall, 5019 patients were delabeled. Using allergy history alone, 14% (95% confidence interval [CI], 9-21%) of 4350 assessed patients were delabeled without reported harm. Direct drug provocation testing resulted in delabeling in 27% (95% CI, 18-37%) of 4207 assessed patients. Of the 1373 patients tested, 98% were delabeled (95% CI, 97-99%), and nonserious harm was reported in 1% (95% CI, 0-2%). Using skin testing, followed by drug provocation testing, 41% (95% CI, 24-59%) of 2890 assessed patients were delabeled. Of the 1294 tested patients, 95.0% (95% CI, 90-99%) were delabeled, and the reported harm was low (0%; (95% CI 0-1%).
CONCLUSION
Penicillin allergy delabeling by nonallergists is efficacious and safe. The proportion of assessed patients who can be delabeled increases with the complexity of testing method, but substantial numbers can be delabeled without skin testing.
Topics: Humans; Adult; Child; Penicillins; Drug Hypersensitivity; Skin Tests; Delivery of Health Care; Hypersensitivity; Anti-Bacterial Agents
PubMed: 36450321
DOI: 10.1016/j.ijid.2022.11.026 -
Orphanet Journal of Rare Diseases Apr 2021Hepatic Actinomycosis (HA) is one of the infections that causes disorders in patients when diagnosed untimely and inappropriately. (Review)
Review
BACKGROUND
Hepatic Actinomycosis (HA) is one of the infections that causes disorders in patients when diagnosed untimely and inappropriately.
METHODS
Case reports on HA in patients published between 2000 and April 2020 were gathered by carrying out a structured search through PubMed/Medline.
RESULTS
Through a survey of the Medline database, 130 studies were identified and then, 64 cases with HA were included in the final analysis. Asia had the largest share of cases with 37.5% (24 reports), followed by Europe and the Americas. Affected patients were predominantly males (64%) and the overall mortality rate was 1% with only one male patient in his 50 s dying. Nearly all patients (92%) were immunocompetent. However, in four patients, the use of immunosuppressive medication led to depression of the immune system. Most of the patients (80%) experienced complications. In terms of the complications, the most frequent ones were previous history of abdominal surgery (32%) and foreign bodies in the abdominopelvic region (20%). Actinomyces israelii was the most common pathogen isolated from patients. Abdominal pain (66%), fever (62%), weight loss (48%), night sweat, malaise, and anorexia (14%) over about 3.1 months were the most frequently reported clinical symptoms. Extension to one or more surrounding organs was evident in 18 patients (28%). Histopathologic examination confirmed infection in 67% of the patients and samples obtained from liver puncture biopsy (32%) were most frequently used in diagnosis. Surgery or puncture drainage + anti-infection was the most common method to treat patients and penicillin, Amoxicillin, Doxycycline, and ampicillin were the most frequently used drugs to control infection.
CONCLUSION
HA should be considered in patients with a subacute or chronic inflammatory process of the liver. With accurate and timely diagnosis of infection, extensive surgery can be prevented.
Topics: Actinomyces; Actinomycosis; Asia; Europe; Humans; Male
PubMed: 33931097
DOI: 10.1186/s13023-021-01821-5 -
European Journal of Drug Metabolism and... Mar 2022Methotrexate (MTX) is widely used for the treatment of a variety of neoplastic and autoimmune diseases. However, its toxicity and efficacy varied greatly among...
BACKGROUND AND OBJECTIVES
Methotrexate (MTX) is widely used for the treatment of a variety of neoplastic and autoimmune diseases. However, its toxicity and efficacy varied greatly among individuals, and they could be predicted by its pharmacokinetics. Many population pharmacokinetic models have been published to describe MTX pharmacokinetics. The objective of this systematic review was to summarize and discuss covariates with significant influence on MTX pharmacokinetics.
METHODS
We searched PubMed and EMBASE databases from their inception to April 2021 for population pharmacokinetic of MTX. The articles were screened by inclusion and exclusion criteria. The characteristics of studies and information for model construction and validation were extracted, summarized and discussed.
RESULTS
Thirty-five articles were included. The two-compartment model well described the pharmacokinetic behavior of MTX. For inter-individual variability, an exponential distribution error model was usually used for high-dose MTX population pharmacokinetic models, while a proportional distribution error model was used for low-dose MTX population pharmacokinetic models. Proportional and combined proportional and additive error models were used to describe residual error. Renal function was an independent indicator of MTX clearance. Body weight, age, gene polymorphisms (SLCO1B1, ABCC2, ABCB1, ABCG2 and MTHFR) and co-medications (proton pump inhibitors, non-steroidal anti-inflammatory drug, dexamethasone, vancomycin, penicillin and salicylic acid) could influence MTX clearance. Body weight, body surface area, age and dosage regimen have significant influence on MTX central compartment volume. Internal bootstrap test, external validation and visual predictive check were used to evaluate model predictive ability.
CONCLUSIONS
Various covariates could affect MTX pharmacokinetics, and their relationships have been summarized and discussed. This review will be helpful for researchers to develop their own population pharmacokinetic models and select appropriate models for individualized therapy of MTX.
Topics: Antimetabolites, Antineoplastic; Body Surface Area; Humans; Liver-Specific Organic Anion Transporter 1; Methotrexate; Models, Biological; Polymorphism, Genetic
PubMed: 34985725
DOI: 10.1007/s13318-021-00737-6 -
Archives of Dermatological Research Jun 2024Streptococcal infections may contribute to psoriasis development, and antistreptococcal treatments are considered potential therapies, but their effectiveness remains... (Review)
Review
Streptococcal infections may contribute to psoriasis development, and antistreptococcal treatments are considered potential therapies, but their effectiveness remains uncertain due to limited systematic evidence. Our objective was to analyze antistreptococcal therapies' effectiveness in improving psoriasis. We conducted a systematic review following PRISMA guidelines, evaluating antistreptococcal treatment efficacy in psoriasis patients from PubMed, Scopus, and Embase databases until August 14, 2022. Eligible studies included psoriasis patients undergoing antistreptococcal therapy, regardless of demographics or psoriasis type. 50 studies (1778 patients) were analyzed, with penicillins/aminopenicillins as the most studied antibiotics (21 studies), showing mixed outcomes, some reporting significant improvement in guttate psoriasis, while others showed no significant difference. Rifampin demonstrated positive results in most of ten studies, and macrolides showed varying effectiveness in two studies. Tonsillectomy in 14 studies (409 patients) mainly focusing on guttate and chronic plaque psoriasis showed positive outcomes, indicating improved symptoms and quality of life. Limitations include heterogeneous studies, sampling bias, and quality of evidence. This systematic review reveals limited and varied evidence for systemic antibiotic therapy efficacy in psoriasis treatment, while tonsillectomy emerges as a potentially beneficial antistreptococcal option, urging further well-designed, controlled studies with larger sample sizes and standardized protocols for better comparisons.
Topics: Humans; Psoriasis; Anti-Bacterial Agents; Streptococcal Infections; Treatment Outcome; Quality of Life; Penicillins; Rifampin
PubMed: 38850287
DOI: 10.1007/s00403-024-03051-8 -
International Journal of Antimicrobial... Aug 2023Carbapenem-sparing antibiotics are needed urgently for patients with complicated intra-abdominal infections (cIAIs). Although several novel antibiotics - novel... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Carbapenem-sparing antibiotics are needed urgently for patients with complicated intra-abdominal infections (cIAIs). Although several novel antibiotics - novel β-lactam/β-lactamase inhibitor combinations (e.g. ceftolozane-tazobactam and ceftazidime-avibactam) and a novel tetracycline derivative (eravacycline) - have been developed for cIAIs, it remains unclear whether these antibiotics are comparable to carbapenems for the treatment of cIAIs.
METHODS
A comprehensive search of PubMed, Embase, Cochrane Library and ClinicalTrials.gov was conducted until 1 October 2022. Only randomized controlled trials (RCTs) that compared the clinical efficacy and safety of novel antibiotics against carbapenems for patients with cIAIs were included.
RESULTS
Among the 11 selected RCTs, no significant differences in clinical cure rate at the test-of-cure visit were observed between the study group and the control group on analysis of the clinically evaluable population [93.6% vs 93.7%, risk ratio (RR) 1.00, 95% confidence interval (CI) 0.98-1.01; P=0.84], microbiologically evaluable population (93.0% vs 94.5%, RR 0.98, 95% CI 0.96-1.00; P=0.10) and modified intention-to-treat population (85.9% vs 87.7%, RR 0.98, 95% CI 0.95-1.01; P=0.13). All findings were consistent across the subgroup analyses and sensitivity tests. Similarly, no significant difference in microbiological eradication was observed between the study group and the control group (87.8% vs 89.7%, RR 0.98, 95% CI 0.96-1.01; P=0.18). The risk of adverse events was similar in both groups.
CONCLUSIONS
Clinical efficacy, microbiological response and safety of the novel antibiotics, including ceftazidime-avibactam, ceftolozane-tazobactam and eravacycline, are comparable to carbapenems for the treatment of patients with cIAIs. These agents can be potential therapeutic options as carbapenem-sparing antibiotics for cIAIs.
Topics: Humans; Anti-Bacterial Agents; Carbapenems; Randomized Controlled Trials as Topic; Ceftazidime; Intraabdominal Infections; Tazobactam; beta-Lactamase Inhibitors; Drug Combinations; Azabicyclo Compounds
PubMed: 37160243
DOI: 10.1016/j.ijantimicag.2023.106844 -
European Journal of Hospital Pharmacy :... Dec 2023Extended infusion (EI) of beta-lactam antibiotics may offer clinical benefits aligned with improved probability of target attainment for critical...
BACKGROUND
Extended infusion (EI) of beta-lactam antibiotics may offer clinical benefits aligned with improved probability of target attainment for critical pharmacokinetic/pharmacodynamic parameters that correlate with efficacy. There is much research interest in prolonged and continuous infusions (collectively, extended infusions) of beta-lactams to improve patient outcomes, particularly in critically ill patients in intensive care. While definitive clinical trial data demonstrating beneficial outcomes is awaited, there has been limited focus on the stability of the agents given by EI, which may be an equally critical parameter. EI may allow for savings in nursing time due to reduced need for drug reconstitution. We set out to examine the data for stability for EI at room temperature, consistent with the requirements of 'A Standard Protocol for Deriving and Assessment of Stability- Part 1 Aseptic Preparation (Small Molecules)', which allows a 5% loss of active pharmaceutical ingredient (API) applicable for those territories that use the British Pharmacopoeia also for a 10% loss applicable in much of rest of the world.
METHODS
Searches using preferred reporting items for systematic reviews and meta-analyses (PRISMA) principles for stability data on freshly prepared beta-lactam antimicrobials for extended administration at room temperature (at or above 23°C) were conducted in November 2021 and updated in December 2022.
RESULTS
We found data to support the extension of the shelf life of 12 key beta-lactam antibiotics once reconstituted (aztreonam, amoxicillin, benzylpenicillin, flucloxacillin, piperacillin/tazobactam, cefazolin, cefmetazole, ceftaroline, ceftazidime, ceftriaxone, imipenem and meropenem) compliant with the NHS protocol, and data for five other agents (ticarcillin, cefepime, cefiderocol, cefoxitin and doripenem) which would be acceptable in regions outside the UK beyond that listed in the Summary of Product Characteristics.This review has not been registered under PROSPERO.
Topics: Humans; Anti-Bacterial Agents; beta Lactam Antibiotics; Inpatients; Temperature; Ceftazidime
PubMed: 37848286
DOI: 10.1136/ejhpharm-2023-003855 -
The Canadian Journal of Infectious... 2024Unreserved use of antibiotics exerted selective pressure on susceptible bacteria, resulting in the survival of resistant strains. Despite this, the relationship between... (Review)
Review
BACKGROUND
Unreserved use of antibiotics exerted selective pressure on susceptible bacteria, resulting in the survival of resistant strains. Despite this, the relationship between antibiotic resistance (ABR) and antibiotic consumption (ABC) is rarely studied. This systematic review aims to review the relationship between ABC and ABR from 2016 to 2022.
METHODS
Articles published over 7 years (2016-2022) were searched from December 23 to 31, 2022. The search strategy was developed by using keywords for ABC and ABR. From 3367 articles, 58 eligible articles were included in the final review.
RESULTS
The pooled ABC was 948017.9 DPDs and 4108.6 DIDs where over 70% of antibiotics were from the Watch and Reserve category based on the WHO AWaRe classification. The average pooled prevalence of ABR was 38.4%. (59.4%), (52.6%), and (48.6%) were the most common antibiotic-resistant bacteria. Cephalosporins (76.8%), penicillin (58.3%), and aminoglycosides (52%) were commonly involved antibiotics in ABR. The positive correlation between ABR and consumption accounted for 311 (81%). The correlation between ABR and ABC accounted for 87 (22.7%), followed by 78 (20.3%) and 77 (20.1%) for ABR and with ABCs, respectively. Consumption of carbapenems and fluoroquinolones was most commonly correlated with resistance rates of , , , and .
CONCLUSION
There is a positive correlation between ABC and the rate of ABR. The review also revealed a cross-resistance between the consumption of different antibiotics and ABR. Optimizing antibiotic therapy and reducing unnecessary ABC will prevent the emergence and spread of ABR. Thus, advocating the implementation of stewardship programs plays a pivotal role in containing ABR.
PubMed: 38476862
DOI: 10.1155/2024/9958678