Evaluation of Early Tocilizumab Effect on Multiorgan Dysfunction in Critically Ill Patients With COVID-19: A Propensity Score-Matched Study.

Background: Tocilizumab (TCZ) has been proposed as potential rescue therapy for severe COVID-19. No previous study has primarily assessed the role of TCZ in preventing severe COVID-19-related multiorgan dysfunction. Hence, this multicenter cohort study aimed to evaluate the effectiveness of TCZ early use versus standard of care in preventing severe COVID-19-related multiorgan dysfunction in COVID-19 critically ill patients during intensive care unit (ICU) stay. Methods: A multicenter, retrospective cohort study includes critically ill adult patients with COVID-19 admitted to the ICUs. Patients were categorized into two groups, the treatment group includes patients who received early TCZ therapy within 24 hours of ICU admission and the control group includes patients who received standard of care. The primary outcome was the multiorgan dysfunction on day three of the ICU admission. The secondary outcomes were 30-day, and in-hospital mortality, ventilator-free days, hospital length of stay (LOS), ICU LOS, and ICU-related complications. Results: After propensity score matching, 300 patients were included in the analysis based on predefined criteria with a ratio of 1:2. Patients who received TCZ had lower multiorgan dysfunction score on day three of ICU admission compared to the control group (beta coefficient: -0.13, 95% CI: -0.26, -0.01, P-value = 0.04). Moreover, respiratory failure requiring MV was statistically significantly lower in patients who received early TCZ compared to the control group (OR 0.52; 95% CI 0.31, 0.91, P-value = 0.02). The 30-day and in-hospital mortality were significantly lower in patients who received TCZ than those who did not (HR 0.56; 95% CI 0.37, 0.85, P-value = 0 .006 and HR 0.54; 95% CI 0.36, 0.82, P-value = 0.003, respectively). Conclusion: In addition to the mortality benefits associated with early TCZ use within 24 hours of ICU admission, the use of TCZ was associated with a significantly lower multiorgan dysfunction score on day three of ICU admission in critically ill patients with COVID-19.

Antibiotics in the pipeline: a literature review (2017-2020).

INTRODUCTION: Antimicrobial resistance (AMR) is an emerging global threat. It increases mortality and morbidity and strains healthcare systems. Health care professionals can counter the rising AMR by promoting antibiotic stewardship and facilitating new drug development. Even with the economic and scientific challenges, it is reassuring that new agents continue to be developed. METHODS: This review addresses new antibiotics in the pipeline. We conducted a review of the literature including Medline, Clinicaltrials.org, and relevant pharmaceutical companies for approved and in pipeline antibiotics in phase 3 or new drug application (NDA). RESULTS: We found a number of new antibiotics and reviewed their current development status, mode of action, spectra of activity, and indications for which they have been approved. The included studies from phase 3 clinical trials were mainly utilized for the treatment of acute bacterial skin and skin structure infections, community-acquired bacterial pneumonia, and pneumonia acquired in the healthcare settings. The number of these agents is limited against high priority organisms. The identified antibiotics were based mainly on previously known molecules or pre-existing antimicrobial agents. CONCLUSION: There are a limited number of antibiotics against high priority organisms such as multi-drug-resistant Pseudomonas aeruginosa, and carbapenem-resistant Enterobacteriaceae. New antimicrobial agents directed against the top priority organisms as classified by the World Health Organization are urgently needed.

Molecular epidemiology and outcome of carbapenem-resistant Enterobacterales in Saudi Arabia.

BACKGROUND: The burden of carbapenem resistance is not well studied in the Middle East. We aimed to describe the molecular epidemiology and outcome of carbapenem-resistant Enterobacterales (CRE) infections from several Saudi Arabian Centers. METHODS: This is a multicenter prospective cohort study conducted over a 28-month period. Patients older than 14 years of age with a positive CRE Escherichia coli or Klebsiella pneumoniae culture and a clinically established infection were included in this study. Univariate and multivariable logistic models were constructed to assess the relationship between the outcome of 30-day all-cause mortality and possible continuous and categorical predictor variables. RESULTS: A total of 189 patients were included. The median patient age was 62.8 years and 54.0% were male. The most common CRE infections were nosocomial pneumonia (23.8%) and complicated urinary tract infection (23.8%) and 77 patients (40.7%) had CRE bacteremia. OXA-48 was the most prevalent gene (69.3%). While 100 patients (52.9%) had a clinical cure, 57 patients (30.2%) had died within 30 days and 23 patients (12.2%) relapsed. Univariate analysis to predict 30-day mortality revealed that the following variables are associated with mortality: older age, high Charlson comorbidity index, increased Pitt bacteremia score, nosocomial pneumonia, CRE bacteremia and diabetes mellitus. In multivariable analysis, CRE bacteremia remained as an independent predictor of 30 day all-cause mortality [AOR and 95% CI = 2.81(1.26-6.24), p = 0.01]. CONCLUSIONS: These data highlight the molecular epidemiology and outcomes of CRE infection in Saudi Arabia and will inform future studies to address preventive and management interventions.

Efficacy of erythromycin compared to clarithromycin and azithromycin in adults or adolescents with community-acquired pneumonia: A Systematic Review and meta-analysis of randomized controlled trials.

BACKGROUND: It is debatable whether erythromycin has similar efficacy to other macrolides in treating community-acquired pneumonia (CAP). The aim of this meta-analysis is to compare the efficacy of erythromycin with clarithromycin and azithromycin. METHODS: We performed this meta-analysis of randomized controlled trials (RCTs) of adults or adolescents with CAP which compared the efficacy of erythromycin monotherapy to either azithromycin or clarithromycin. We searched PubMed and EMBASE and Cochrane Library databases and three clinical trial registries up to November 02, 2021. We evaluated heterogeneity and used random-effects models to perform risk ratios with 95% confidence intervals. RESULTS: We included four RCTs (total of 472 patients), which compared the clinical efficacy of erythromycin versus clarithromycin. No studies comparing monotherapy of erythromycin versus azithromycin were found. Erythromycin use was associated with significantly lower rates of clinical success (RR, 0.79; 95% CI, 0.64 to 0.98; P-value = 0.033; I2 = 20.27%), clinical cure (RR,0.67; 95% CI, 0.48 to 0.92; P-value = 0.014; I2 = 8.75%), and radiological success (RR, 0.84; 95% CI, 0.71 to 0.996; P-value = 0.045; I2 = 20.12%) than clarithromycin. CONCLUSION: Erythromycin is less effective than clarithromycin as empiric treatment of CAP in adults and adolescents. Because of this and the higher rate of adverse reactions, erythromycin should not be used in the majority of CAP patients when azithromycin and clarithromycin are available.

An Overview on Phenotypic and Genotypic Characterisation of Carbapenem-Resistant Enterobacterales.

Improper use of antimicrobials has resulted in the emergence of antimicrobial resistance (AMR), including multi-drug resistance (MDR) among bacteria. Recently, a sudden increase in Carbapenem-resistant Enterobacterales (CRE) has been observed. This presents a substantial challenge in the treatment of CRE-infected individuals. Bacterial plasmids include the genes for carbapenem resistance, which can also spread to other bacteria to make them resistant. The incidence of CRE is rising significantly despite the efforts of health authorities, clinicians, and scientists. Many genotypic and phenotypic techniques are available to identify CRE. However, effective identification requires the integration of two or more methods. Whole genome sequencing (WGS), an advanced molecular approach, helps identify new strains of CRE and screening of the patient population; however, WGS is challenging to apply in clinical settings due to the complexity and high expense involved with this technique. The current review highlights the molecular mechanism of development of Carbapenem resistance, the epidemiology of CRE infections, spread of CRE, treatment options, and the phenotypic/genotypic characterisation of CRE. The potential of microorganisms to acquire resistance against Carbapenems remains high, which can lead to even more susceptible drugs such as colistin and polymyxins. Hence, the current study recommends running the antibiotic stewardship programs at an institutional level to control the use of antibiotics and to reduce the spread of CRE worldwide.

The effect of erythromycin and clarithromycin versus azithromycin on serum valproate concentration.

Introduction: Unlike azithromycin, erythromycin and clarithromycin strongly inhibit CYP450, which metabolizes valproic acid. The aim of this study was to evaluate the impact of macrolide administration on serum valproate trough levels. Methods: This retrospective cohort study included hospitalized adult patients who concomitantly received valproate with a macrolide. Patients who received a carbapenem, those who do not have a baseline and/or post-levels, and those who received different doses of valproate were excluded. The change in serum valproate trough level from baseline to after the occurrence of co-administration (post-level) was compared in patients who received either erythromycin or clarithromycin versus those who received azithromycin. Results: A total of thirteen patients were included in the comparison. The mean ± SD for change in serum valproate trough levels was significantly higher in the erythromycin/clarithromycin group than the azithromycin group (209.1 ± 105.9 µmol/L [equivalent to 30.1 ± 15.2 mg/L] vs. 12.7 ± 52.1 µmol/L [equivalent to 1.8 ± 7.5 mg/L]; P = 0.002). Conclusion: This study found a significantly higher increase in serum trough levels of valproate after co-administration of erythromycin/clarithromycin versus azithromycin. Clinicians should consider avoiding co-administration of erythromycin and clarithromycin with valproate if possible or close monitoring of valproate levels with dose reduction.

Infectious diseases pharmacy practice, education, and research in Saudi Arabia: A review and future perspectives by the Infectious Diseases Pharmacy Specialty Network at the Saudi Society of Clinical Pharmacy.

Background: Infectious diseases (ID) pharmacy is one of the rapidly evolving clinical pharmacy specialties in the Kingdom of Saudi Arabia (KSA). There are gaps in the literature on ID pharmacy status in KSA. This review aimed to provide an update on the current status of several areas related to ID pharmacy in KSA, including practice, education, and research, and make pertinent recommendations for future development to achieve the KSA Vision, 2030, KSA Vision, 2030. Methods: This review was developed by a group of ID pharmacists working in different sectors under the umbrella of the ID Pharmacy Specialty Network (PSN) of the Saudi Society of Clinical Pharmacy (SSCP). The authors evaluated domains related to ID pharmacy in KSA and searched the literature for relevant articles. Based on the experts' assessment of the current gaps and challenges, recommendations were made for future improvement. Results: Several aspects of ID pharmacy in KSA were evaluated, including history and development, antimicrobial resistance (AMR), antimicrobial stewardship programs (ASP), roles of ID pharmacists, ID pharmacy education, and research. The biggest challenges include AMR, the varying levels of ASP implementation, and the low number of ID-trained pharmacists, especially in non-major cities. Several recommendations for improvement were discussed. Conclusion: Infectious diseases pharmacy has sustained remarkable progress in KSA in several areas. However, more efforts are needed to increase ASP implementation, increase the number of ID-trained pharmacists, and encourage ID pharmacists in publishing and participating in practice guidelines, which will eventually help achieve the KSA Vision, 2030, KSA Vision, 2030.

Comparison between standard Vs. Escalated dose venous thromboembolism (VTE) prophylaxis in critically ill patients with COVID-19: A two centers, observational study.

INTRODUCTION: The risk of mortality in patients with COVID-19 was found to be significantly higher in patients who experienced thromboembolic events. Thus, several guidelines recommend using prophylactic anticoagulants in all COVID-19 hospitalized patients. However, there is uncertainty about the appropriate dosing regimen and safety of anticoagulation in critically ill patients with COVID-19. Thus, this study aims to compare the effectiveness and safety of standard versus escalated dose pharmacological venous thromboembolism (VTE) prophylaxis in critically ill patients with COVID-19. METHODS: A two-center retrospective cohort study including critically ill patients aged ≥ 18-years with confirmed COVID-19 admitted to the intensive care unit (ICU) at two tertiary hospitals in Saudi Arabia from March 1st, 2020, until January 31st, 2021. Patients who received either Enoxaparin 40 mg daily or Unfractionated heparin 5000 Units three times daily were grouped under the "standard dose VTE prophylaxis and patients who received higher than the standard dose but not as treatment dose were grouped under "escalated VTE prophylaxis dose". The primary outcome was the occurance of thrombotic events, and the secondary outcomes were bleeding, mortality, and other ICU-related complications. RESULTS: A total of 758 patients were screened; 565 patients were included in the study. We matched 352 patients using propensity score matching (1:1). In patients who received escalated dose pharmacological VTE prophylaxis, any case of thrombosis and VTE were similar between the two groups (OR 1.22;95 %CI 0.52-2.86; P = 0.64 and OR 0.75; 95% CI 0.16-3.38; P = 0.70 respectively). However, the odds of minor bleeding was higher in patients who received escalated VTE prophylaxis dose (OR 3.39; 95% CI 1.08-10.61; P = 0.04). There was no difference in the 30-day mortality nor in-hospital mortality between the two groups (HR 1.17;95 %CI0.79-1.73; P = 0.43 and HR 1.08;95 %CI 0.76-1.53; P = 0.83, respectively). CONCLUSION: Escalated-dose pharmacological VTE prophylaxis in critically ill patients with COVID-19 was not associated with thrombosis, or mortality benefits but led to an increased risk of minor bleeding. This study supports previous evidence regarding the optimal dosing VTE pharmacological prophylaxis regimen for critically ill patients with COVID-19.

Association between tocilizumab and emerging multidrug-resistant organisms in critically ill patients with COVID-19: A multicenter, retrospective cohort study.

BACKGROUND: Tocilizumab is an IgG1 class recombinant humanized monoclonal antibody that directly inhibits the IL-6 receptor. Several randomized clinical trials have evaluated its safety and efficacy in patients with coronavirus disease 2019 (COVID-19), and these studies demonstrate conflicting results. Our study aimed to determine the association between tocilizumab treatment and microbial isolation and emergence of multidrug-resistant bacteria in critically ill patients with COVID-19. METHODS: A multicenter retrospective cohort study was conducted at two tertiary government hospitals in Saudi Arabia. All critically ill patients admitted to intensive care units with a positive COVID-19 PCR test between March 1 and December 31, 2020, who met study criteria were included. Patients who received tocilizumab were compared to those who did not receive it. RESULTS: A total of 738 patients who met our inclusion criteria were included in the analysis. Of these, 262 (35.5%) received tocilizumab, and 476 (64.5%) were included in the control group. Patients who received tocilizumab had higher odds for microbial isolation (OR 1.34; 95% CI 0.91-1.94, p = 0.13); however, the difference was not statistically significant. Development of resistant organisms (OR 1.00; 95% CI 0.51-1.98, p = 0.99) or detection of carbapenem-resistant Enterobacteriaceae (CRE) (OR 0.67; 95% CI 0.29-1.54, p = 0.34) was not statistically significant between the two groups. CONCLUSIONS: Tocilizumab use in critically ill patients with COVID-19 is not associated with higher microbial isolation, the emergence of resistant organisms, or the detection of CRE organisms.

Safety and efficacy of colistin and fluoroquinolone in neonatal persistent late-onset sepsis.

Growing resistance of microorganisms to antibiotics for the treatment of late-onset sepsis (LOS) in premature infants has led physicians to use antibiotics that are not well studied in neonatal populations. We aimed to determine the efficacy and safety of colistin and fluoroquinolone for the treatment of persistent LOS. We retrospectively reviewed infants with gram-negative LOS, who received either colistin or fluoroquinolone therapy, to determine if there was a significant difference in kidney and liver function tests and electrolyte levels before, during, and at the end of the treatment. Infants who received colistin and fluoroquinolone had 17 and 34 positive cultures with gram-negative organisms, respectively. Multi-drug resistant organisms were more common in infants who received colistin than in those who received fluoroquinolone. Microbiological clearance was found to be higher in infants treated with fluoroquinolone than in those treated with colistin. In both the groups, the median levels of kidney and liver function tests and electrolytes showed a significant increase during the treatment. The prescription of colistin and fluoroquinolones should be reserved for cases with no other safe and effective alternatives.

Efficacy of clotrimazole for the management of oral candidiasis: A meta-analysis of randomized clinical trials.

PURPOSE: To assess the efficacy and safety of topical application of clotrimazole versus others in the treatment of oropharyngeal candidiasis (OPC). METHOD: Four electronic databases, registries of ongoing trials, and manual search were used to identify randomized controlled trials (RCTs) that compared the efficacy of clotrimazole to other antifungal agents in patients who were clinically diagnosed with oral candidiasis up to November 1st, 2019. Primary outcomes were clinical response and mycological cure rates. Secondary outcomes include relapse rate, incidence of systemic infections, and compliance. Adverse effects were also evaluated. RESULTS: Sixteen RCTs with a total of 1685 patients were included. Half of the eligible studies were considered at high risk of performance bias and more than a third, at high risk of reporting bias. Our analysis showed no significant difference in clinical response between clotrimazole and all other antifungal agents. However, clotrimazole was less effective in terms of mycologic cure and relapse rate. Sensitivity analysis comparing clotrimazole to other topical antifungal agents only showed no differences in clinical response, microbiologic cure or relapse. Further sensitivity analysis showed significant efficacy of fluconazole over clotrimazole. CONCLUSION: This meta-analysis indicated that clotrimazole is less effective than fluconazole but as effective as other topical therapies in treating OPC. Well-designed high-quality RCT is needed to validate these findings.

Clinical pharmacy definition, required education, training and practice in Saudi Arabia: A position statement by the Saudi society of clinical pharmacy.

The Saudi Society of Clinical Pharmacy (SSCP) is a scientific and professional society in the field of clinical pharmacy that operates under the Saudi Commission for Health Specialties governance. The SSCP believes that there is a need to define and describe many aspects related to the clinical pharmacy profession in Saudi Arabia. Moreover, there is an increasing demand for promoting the concept of clinical pharmacy and developing a consensus regarding the scope of practice and clinical pharmacist's required postgraduate education and training in Saudi Arabia. This paper is intended to present several position statements by the SSCP that define the concept of clinical pharmacy, describe the required education and training, and highlight clinical pharmacists' scope of practice in Saudi Arabia. This paper calls for further investigations that examine the impact of clinical pharmacists on individual and population health levels.

Cefdinir-induced red stool and purple discoloration of nutritional formula: A case report.

This case report describes a 4-year-old girl with food aversion who received three separate courses of cefdinir mixed with PediaSure®, an iron-fortified nutritional formula. The patient's stool turned red with variable onset during all three courses of treatment. Moreover, the PediaSure® formula turned purple after mixed with cefdinir, an interaction that has not been previously reported. We recommend that medication counseling for pediatric patients taking cefdinir include a mention of these possible discolorations.

Photosensitivity induced by lomefloxacin versus other fluoroquinolones: A meta-analysis.

Lomefloxacin may be more likely than other fluoroquinolones to cause photosensitivity. However, the rate of photosensitivity is variable and a meta-analysis has yet to be performed. The aim of this meta-analysis is to compare the rate of photosensitivity between outpatients who received lomefloxacin and those who received other fluoroquinolones. PubMed, EMBASE, Cochrane Library databases and trial registries were searched for randomized controlled trials (RCTs) of outpatients through June 12, 2019. The study outcome was the rate of photosensitivity based on the intention-to-treat principle, estimated by risk difference (RD) as the primary analysis and Peto odds ratio (Peto OR) as the secondary analysis, with 95% confidence intervals (CIs) using random-effects models. Four RCTs (total of 2295 patients) were included in this meta-analysis. A statistically higher risk of photosensitivity was found with lomefloxacin than with other fluoroquinolones (RD, 3.4%; 95% CI, 0.7%-6.2%; P-value = 0.013; I2 = 10.9%). The odds of photosensitivity was also significantly higher with lomefloxacin (Peto OR, 5.81; 95% CI, 3.34 to 10.11; P-value <0.001; I2 = 0%). This meta-analysis of RCTs found significantly higher photosensitivity with lomefloxacin compared to other fluoroquinolones. Considering this finding and given its lack of additional efficacy compared to other fluoroquinolones, lomefloxacin as a fluoroquinolone option should potentially be reconsidered.

Systematic Review and Meta-analysis of the Safety of Antistaphylococcal Penicillins Compared to Cefazolin.

Recent studies and experience suggest that cefazolin might be equally as effective as antistaphylococcal penicillins for methicillin-susceptible Staphylococcus aureus (MSSA), with a better safety profile and lower cost. The objective of these meta-analyses was to compare the safeties of antistaphylococcal penicillins and cefazolin. The PubMed, Embase, and International Pharmaceutical Abstracts databases and websites for clinical trial registries through 23 June 2017 were searched. In addition, recent abstracts from infectious disease and pharmacy conferences were reviewed. We estimated Peto odds ratios (ORs) with 95% confidence intervals (CIs) using random-effects models. One analysis focused on hospitalized patients, and the other focused on outpatients. Eleven retrospective studies of hospitalized patients and three retrospective studies of outpatients were included. In hospitalized patients, lower rates of nephrotoxicity (Peto OR, 0.225; 95% CI, 0.127 to 0.513), acute interstitial nephritis (Peto OR, 0.189; 95% CI, 0.053 to 0.675), hepatotoxicity (Peto OR, 0.160; 95% CI, 0.066 to 0.387), and drug discontinuation due to adverse reactions (Peto OR, 0.192; 95% CI, 0.089 to 0.414) were found with cefazolin. In outpatients, lower rates of nephrotoxicity (Peto OR, 0.372; 95% CI, 0.192 to 0.722), hepatotoxicity (Peto OR, 0.313; 95% CI, 0.156 to 0.627), and hypersensitivity reactions (Peto OR, 0.372; 95% CI, 0.201 to 0.687) were observed with cefazolin. Compared to antistaphylococcal penicillins, cefazolin was associated with significant reductions in nephrotoxicity and hepatotoxicity in hospitalized patients and outpatients. Additionally, cefazolin was associated with lower likelihoods of discontinuation due to side effects in hospitalized patients and hypersensitivity reactions in outpatients. Cefazolin should be considered a first-line option for patients with MSSA infections for which efficacy is presumed to be similar to that of antistaphylococcal penicillin therapy.

Impact of requiring re-authorization of restricted antibiotics on day 3 of therapy.

Background: Pre-authorization of restricted antibiotics is a core component of an antibiotic stewardship programme (ASP). On day 3, information about culture results and clinical status is typically available. Our objective was to compare an ASP that requires initial authorization alone with one requiring initial authorization and re-authorization on day 3 of therapy. Methods: A single-centre, retrospective, before and after study was conducted. Randomly selected adults were eligible if receiving a restricted antibiotic for ≥3 days during April to June in 2012 (pre-intervention) and during the same months in 2013 (post-intervention). The target sample size was 166 patients. The intervention required re-authorization of restricted antibiotics that were continuing on day 3. The days of therapy of restricted antibiotic(s), length of hospital stay (LOS) and hospital mortality were compared between pre- and post-intervention periods. Results: The ASP intervention was associated with a decrease in median days of therapy from 5 (4-9) to 4 (3-5) days (P < 0.001) for all restricted agents, from 5 (3-6) to 3 (3-5) days for broad-spectrum Gram-negative agents (P < 0.001) and from 6.5 (6-7) to 3 (3-4.5) days for oral vancomycin. The proportion of subjects receiving restricted agents for >4 days decreased from 57.8% to 30.1% (P < 0.001). LOS decreased from 8 (5-17) to 6 (5-9) days (P = 0.005) without a significant change in hospital mortality. Conclusions: Requiring re-authorization of restricted antibiotics on day 3 of therapy in addition to initial authorization was associated with reduction in overall consumption of restricted antibiotics and LOS without adversely affecting hospital mortality.

Impact of carbapenem versus non-carbapenem treatment on the rates of superinfection: A meta-analysis of randomized controlled trials.

Imipenem and meropenem are the recommended antipseudomonal carbapenems for nosocomial pneumonia per clinical practice guidelines. However, these agents have a relatively broader spectrum of activity than other antibiotics and need to be reserved. Carbapenems might cause higher rate of superinfection. The aim of this study was to compare the rate of superinfection between patients who received imipenem or meropenem versus those who received non-carbapenem treatment. PubMed, EMBASE, Cochrane Library databases and two trial registries were searched for relevant randomized controlled trials of hospitalized adults with pneumonia through February 24, 2017 without date or language restrictions. Risk ratios (RRs) with 95% confidence intervals (CIs) were estimated using random-effects models. The primary outcome was based on the intention-to-treat analysis while clinically evaluable patients were analyzed as secondary outcome. Eight RCTs were included in this meta-analysis. A statistically higher risk of superinfection with low heterogeneity (RR = 1.690, 95% CI 1.247-2.291, p = 0.001, I2 = 0%) was associated with the two carbapenems compared to non-carbapenems. However, in comparison with non-carbapenems, superinfection with imipenem was significantly higher (RR = 1.694, 95% CI 1.234-2.325, p = 0.001, I2 = 0%), while it was non-significant with meropenem (RR = 1.647, 95% CI 0.552-4.919, p = 0.371, I2 = 0%). Superinfection was statistically higher in both double-blind and open-label studies and when carbapenems were compared to other antipseudomonal beta-lactams. This meta-analysis identified significantly higher superinfection with imipenem compared to non-carbapenems. The findings confirm the theory of higher superinfections with broader spectrum agents and provide additional support for reserving carbapenems for the treatment of infections caused by multidrug-resistant organisms.

Clinical failure with and without empiric atypical bacteria coverage in hospitalized adults with community-acquired pneumonia: a systematic review and meta-analysis.

BACKGROUND: Both typical and atypical bacteria can cause community-acquired pneumonia (CAP); however, the need for empiric atypical coverage remains controversial. Our objective was to evaluate the impact of antibiotic regimens with atypical coverage (a fluoroquinolone or combination of a macrolide/doxycycline with a ß-lactam) to a regimen without atypical antibiotic coverage (ß-lactam monotherapy) on rates of clinical failure (primary endpoint), mortality, bacteriologic failure, and adverse events, (secondary endpoints). METHODS: We searched the PubMed, EMBASE and Cochrane Library databases for relevant RCTs of hospitalized CAP adults. We estimated risk ratios (RRs) with 95% confidence intervals (CIs) using a fixed-effect model, but used a random-effects model if significant heterogeneity (I 2 ) was observed. RESULTS: Five RCTs with a total of 2011 patients were retained. A statistically significant lower clinical failure rate was observed with empiric atypical coverage (RR, 0.851 [95% CI, 0.732-0.99; P = 0.037]; I 2  = 0%). The secondary outcomes did not differ between the two study groups: mortality (RR = 0.549 [95% CI, 0.259-1.165, P = 0.118], I 2  = 61.434%) bacteriologic failure (RR = 0.816 [95% CI, 0.523-1.272, P = 0.369], I 2  = 0%), diarrhea (RR = 0.746 [95% CI, 0.311-1.790, P = 0.512], I 2  = 65.048%), and adverse events requiring antibiotic discontinuation (RR = 0.83 [95% CI, 0.542-1.270, P = 0.39], I 2  = 0%). CONCLUSIONS: Empiric atypical coverage was associated with a significant reduction in clinical failure in hospitalized adults with CAP. Reduction in mortality, bacterial failure, diarrhea, and discontinuation due to adverse effects were not significantly different between groups, but all estimates favored atypical coverage. Our findings provide support for the current guidelines recommendations to include empiric atypical coverage.

Antimicrobial utilization in Hajj 2022: An evaluation of quality indicators.

BACKGROUND: The mass gathering in Hajj (Islamic pilgrimage) makes the spread of infectious diseases inevitable. Antibiotics are frequently prescribed during this season. We aimed to measure antimicrobial utilization during the 2022 Hajj and evaluate the practice using quality indicators. METHODS: Antimicrobial utilization by Hajj medical facilities (77 primary clinics and 7 hospitals) was measured using the anatomic therapeutic classification defined daily dose (DDD) and DDD/1,000-inhabitant/day (DID), where inhabitants were the Hajj 2022 pilgrims (n = 899,353). Quality indicators included percentages of consumption of different antibiotic classes of the total consumption of antibacterials for systemic use in DID. RESULTS: During Hajj, there was 87,173 outpatient visits and 740 hospitalizations (215 critically ill). Amoxicillin was the most prescribed antibiotic (DID=11.708) followed by azithromycin (DID=7.395). Penicillins fell in the second quartile (i.e., highly prescribed) with a quality indicator value (J01_CE%) of 48.149. The consumption of other antibacterials, including fluoroquinolones, fell in the first quartile (<25%). The overall ratio of broad- to narrow-spectrum antibiotic prescribing (J01_B/N) was 1.49. CONCLUSION: Although the prescribing of ß-lactams over fluoroquinolones indicates a good practice, clinicians should be reminded that most infections spreading in mass gatherings are viral; hence, do not require antibiotics. Implementation of antimicrobial stewardship is recommended to improve antimicrobial utilization.