Performance characteristics of genus or species-specific Polymerase Chain Reaction (PCR) for the microbial diagnosis of joint infections: A systematic review and meta-analysis.

Joint infections cause significant morbidity and mortality. Rapid diagnosis enables prompt initiation of appropriate antimicrobial therapy and surgical treatment. We conducted a systematic review and meta-analysis to evaluate the accuracy of genus- or species-specific polymerase chain reaction (PCR) in diagnosing joint infections. The literature databases were searched for articles from January 2010 to December 2022. The meta-analysis using the split component synthesis (SCS) method, included 20 studies with 2,457 adult participants. The pooled sensitivity, specificity, diagnostic odds ratio, and AUC of PCR were 49 % (95 % CI [37.9-60.2]), 95.7 % (95 % CI [91.6-97.8]), 21.32, and 0.82 respectively. Sensitivity was highest for sonicate fluid and lowest for periprosthetic tissue. The mean turnaround time to results was 4.7 hours (SD 1.1). PCR is a favourable option for diagnosing joint infections due to its rapid results, but it has low sensitivity. To enhance diagnostic yield, the test should be used in conjunction with other methods.

Scoping review of risk-scoring tools for early prediction of bloodstream infections caused by carbapenem-resistant Enterobacterales: do we really have a reliable risk-scoring tool?

Background: Bloodstream infections (BSIs) caused by carbapenem-resistant Enterobacterales (CRE) are a global health concern. Rapid identification of CRE may improve patient outcomes and reduce inappropriate antibiotic prescription. The use of risk-scoring tools (RSTs) can be valuable for optimizing the decision-making process for empirical antibiotic therapy of suspected CRE bacteraemia. These tools can also be used to triage use of expensive rapid diagnostic methods. Methods: We systematically reviewed the relevant literature in PubMed/MEDLINE, CINAHL, Cochrane, Web of Science, Embase and Scopus up to 1 November 2022 to identify RSTs that predict CRE BSIs. The literature review and analysis of the articles were performed by two researchers; any inconsistencies were resolved through discussion. Results: We identified 9 RSTs developed for early prediction of CRE BSIs and only logistic regression was used for most studies. These RSTs were quite different from each other in terms of their performance and the variables they included. They also had notable limitations and very few of them were externally validated. Conclusions: RSTs for early prediction of CRE BSIs have limitations and lack of external validity outside the local setting in which they were developed. Future studies to identify optimal RSTs in high and low CRE-endemic settings are warranted. Approaches based on rapid diagnostics and RSTs should be compared with a treatment approach using both methods in a randomized controlled trial.

Pediatric Central Venous Access Device Lock Solutions: A Network Meta-analysis.

CONTEXT: Central venous access device (CVAD) locks are routine interventions used to prevent and treat complications, such as infection, thrombosis, and catheter occlusion. OBJECTIVE: To compare and rank lock-solutions for prevention or treatment of complications in pediatrics. Design Systematic review and network meta-analysis. DATA SOURCES: Five databases and 2 clinical trial registries were searched. STUDY SELECTION: Published and unpublished randomized controlled trials that enrolled pediatric patients with a CVAD and compared the effectiveness of lock-solutions. DATA EXTRACTION: Data extraction was conducted by 2 reviewers. Odds ratio (OR) for prevention or treatment of CVAD-associated bloodstream infection (BSI), thrombosis, occlusion, CVAD-failure, and mortality were calculated, with point estimates ranking lock-solutions. RESULTS: Twenty-nine studies were included. Chelating agents and antibiotic locks given as prevention were associated with lower odds (OR: 0.11; 95% confidence interval [CI]: 0.02-0.67; moderate-quality; OR: 0.19; 95% CI: 0.05-0.79, high-quality, respectively) of CVAD-associated BSI compared with heparinized saline (reference). Preventative thrombolytic agents had lower odds (OR: 0.64, 95% CI: 0.44-0.93; low-quality) of CVAD occlusion, whereas ethanol had higher odds (OR: 2.84, 95% CI: 1.31-6.16; high-quality) compared with heparinized saline (reference). No lock solution had effects on thrombosis prevention or treatment, CVAD-failure, CVAD-associated BSI treatment failure, or mortality. LIMITATIONS: There was substantial uncertainty around the point estimates because of the limited number of studies for outcomes and study heterogeneity. More high-quality studies are needed to confirm the efficacy of lock solutions. CONCLUSIONS: Chelating agents and antibiotic locks may be effective for CVAD-associated BSI prevention in pediatrics. Thrombolytic agents can be an option for CVAD occlusion prevention, whereas ethanol may not be recommended.

In vitro, in vivo and clinical studies comparing the efficacy of ceftazidime-avibactam monotherapy with ceftazidime-avibactam-containing combination regimens against carbapenem-resistant Enterobacterales and multidrug-resistant Pseudomonas aeruginosa isolates or infections: a scoping review.

Introduction: Carbapenem-resistant Enterobacterales (CRE) and multidrug-resistant Pseudomonas aeruginosa (MDR-PA) infections are associated with a high risk of morbidity, mortality, and treatment costs. We aimed to evaluate in vitro, in vivo and clinical studies comparing the efficacy of ceftazidime-avibactam (CZA) combination regimens with CZA alone against CRE and/or MDR-PA isolates or infections. Methods: We systematically reviewed the relevant literature in CINAHL/MEDLINE, Pubmed, Cochrane, Web of Science, Embase, and Scopus until December 1, 2022. Review articles, grey literature, abstracts, comments, editorials, non-peer reviewed articles, non-English articles, and in vitro synergy studies conducted on single isolates were excluded. Results: 22 in vitro, 7 in vivo and 20 clinical studies were evaluated. In vitro studies showed reliable synergy between CZA and aztreonam against metallo-ß-lactamase (MBL)-producing isolates. Some studies indicated good in vitro synergy between CZA and amikacin, meropenem, fosfomycin and polymyxins against CRE isolates. For MDR-PA isolates, there are comparatively fewer in vitro or in vivo studies. In observational clinical studies, mortality, clinical cure, adverse events, and development of CZA resistance after exposure were generally similar in monotherapy and combination therapy groups. However, antibiotic-related nephrotoxicity and infection relapses were higher in patients receiving CZA combination therapies. Discussion: The benefit, if any, of CZA combination regimens in MDR-PA infections is elusive, as very few clinical studies have included these infections. There is no currently documented clinical benefit for the use of CZA combination regimens rather than CZA monotherapy. CZA combined with aztreonam for serious infections due to MBL producers should be evaluated by randomized controlled trials. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=278552, CRD42021278552.

Efficacy and Safety of Carbapenems vs New Antibiotics for Treatment of Adult Patients With Complicated Urinary Tract Infections: A Systematic Review and Meta-analysis.

This systematic review and meta-analysis evaluated the clinical efficacy and safety of carbapenems for the treatment of complicated urinary tract infections (cUTIs), with the comparators being new antibiotics evaluated for this indication. We searched 13 electronic databases for published randomized controlled trials (RCTs) and completed and/or ongoing trials. The search terms were developed using the Population, Intervention, Comparison, Outcomes, and Study framework. Pooled efficacy estimates of composite cure (clinical success and microbiological eradication) favored the new antibiotic groups, although this was not statistically significant (risk ratio [RR], 0.91; 95% CI, 0.79-1.04). A pooled estimate examining clinical response alone showed no difference between treatment arms (RR, 1.00; 95% CI, 0.96-1.05), however, new antibiotic treatments were superior to carbapenems for microbiological response (RR, 0.85; 95% CI, 0.79-0.91). New antibiotic treatments demonstrated a superior microbiological response compared with carbapenems in clinical trials of cUTI, despite an absence of carbapenem resistance. However, it is noteworthy that the clinical response and safety profile of new antibiotics were not different from those of carbapenems.

Adverse clinical outcomes associated with carbapenem-resistant Acinetobacter (CRA) infections: a systematic review and meta-analysis.

BACKGROUND: Carbapenem-resistant Acinetobacter (CRA) infections have been associated with increased morbidity and mortality in hospitalized patients. This systematic review and meta-analysis aimed to quantify the association between CRA infections and adverse clinical outcomes. METHODS: Three databases (i.e. PubMed, EMBASE and Scopus) were searched for epidemiological studies that compared mortality, severe sepsis or shock, or bacteraemia among adult inpatients with CRA infections and those with carbapenem-susceptible Acinetobacter (CSA) infections. The pooled ORs for the three outcomes were estimated using the inverse variance heterogeneity model. RESULTS: Thirty-four studies were included. Patients with CRA infections had higher odds of mortality (31 studies, OR = 2.10, 95% CI: 1.58-2.79, I 2=60.6%) and severe sepsis or septic shock (7 studies, OR = 1.51, 95% CI: 1.09-2.09, I 2=0%) compared with CSA-infected patients. There was no difference in the odds of bacteraemia (four studies, OR = 1.39, 95% CI: 0.79-2.46, I 2=38.1%). CRA-infected patients presented with worse comorbidity at admission (e.g. APACHE score) (eight studies, standardized mean difference = 0.25, 95% CI: -0.01 to 0.52) and had lower frequency of appropriate antibiotic therapy. Results were consistent when pooling 16 study-adjusted risk estimates for mortality. There was no difference in risk of mortality from CRA infection when compared across geographical regions, country income, median year of enrolment and day of mortality from infection onset. CONCLUSIONS: CRA-infected patients had worse clinical outcomes. This might be due to delay in appropriate antibiotic therapy, patients being sicker at admission and CRA strains potentially being more virulent than CSA strains. Improving appropriateness of antibiotic therapy in CRA-infected patients could reduce adverse clinical outcomes.

Gram-negative neonatal sepsis in low- and lower-middle-income countries and WHO empirical antibiotic recommendations: A systematic review and meta-analysis.

BACKGROUND: Neonatal sepsis is a significant global health issue associated with marked regional disparities in mortality. Antimicrobial resistance (AMR) is a growing concern in Gram-negative organisms, which increasingly predominate in neonatal sepsis, and existing WHO empirical antibiotic recommendations may no longer be appropriate. Previous systematic reviews have been limited to specific low- and middle-income countries. We therefore completed a systematic review and meta-analysis of available data from all low- and lower-middle-income countries (LLMICs) since 2010, with a focus on regional differences in Gram-negative infections and AMR. METHODS AND FINDINGS: All studies published from 1 January 2010 to 21 April 2021 about microbiologically confirmed bloodstream infections or meningitis in neonates and AMR in LLMICs were assessed for eligibility. Small case series, studies with a small number of Gram-negative isolates (<10), and studies with a majority of isolates prior to 2010 were excluded. Main outcomes were pooled proportions of Escherichia coli, Klebsiella, Enterobacter, Pseudomonas, Acinetobacter and AMR. We included 88 studies (4 cohort studies, 3 randomised controlled studies, and 81 cross-sectional studies) comprising 10,458 Gram-negative isolates from 19 LLMICs. No studies were identified outside of Africa and Asia. The estimated pooled proportion of neonatal sepsis caused by Gram-negative organisms was 60% (95% CI 55% to 65%). Klebsiella spp. was the most common, with a pooled proportion of 38% of Gram-negative sepsis (95% CI 33% to 43%). Regional differences were observed, with higher proportions of Acinetobacter spp. in Asia and Klebsiella spp. in Africa. Resistance to aminoglycosides and third-generation cephalosporins ranged from 42% to 69% and from 59% to 84%, respectively. Study limitations include significant heterogeneity among included studies, exclusion of upper-middle-income countries, and potential sampling bias, with the majority of studies from tertiary hospital settings, which may overestimate the burden caused by Gram-negative bacteria. CONCLUSIONS: Gram-negative bacteria are an important cause of neonatal sepsis in LLMICs and are associated with significant rates of resistance to WHO-recommended first- and second-line empirical antibiotics. AMR surveillance should underpin region-specific empirical treatment recommendations. Meanwhile, a significant global commitment to accessible and effective antimicrobials for neonates is required.

Cutibacterium acnes in shoulder surgery: a scoping review of strategies for prevention, diagnosis, and treatment.

BACKGROUND: Cutibacterium acnes is a commensal, gram-positive, facultatively anaerobic bacillus that resides in the dermis. Historically thought to be a contaminant when identified on cultured specimens, recent advances in diagnostic technology have now implicated it as the most common organism responsible for postoperative shoulder infections. Despite a recognition of the role of this organism and a significant research interest in recent years, there is clear lack of consensus guideline on strategies to prevent, diagnose, and treat postoperative shoulder infection. METHOD: The electronic databases PubMed, MEDLINE, CINAHL, Scopus, and Web of Science were searched in March 2020. All experimental and nonexperimental studies that investigate C acnes in shoulder surgery were included. Inclusion was limited to articles published after 2000 and written in English; reviews, gray literature, or abstracts were excluded. A total of 70 studies were included in this review. This scoping review was performed in accordance with the Extended Preferred Reporting Items of Systematic Reviews and Meta-Analyses Statement for Scoping Reviews (PRISMA-ScR). RESULTS: Standard surgical prophylactic regimens such as intravenous antibiotics and topical chlorhexidine are ineffective at removing C acnes from the deep layer of the dermis, and there is a shift toward using topical benzoyl peroxide with significantly improved efficacy. An improved understanding of the bacteria has demonstrated that a prolonged culture time of up to 14 days is needed, especially in cases of established infection. Advances in diagnostics such as sonication and molecular-based testing are promising. Although usually thought to be susceptible to a broad range of antibiotics, resistance is emerging to clindamycin. An improved understanding of its ability to form a biofilm highlights the difficulty in treating an established infection. CONCLUSION: The role of C acnes causing postoperative infection following shoulder surgery is being increasingly recognized. Strategies for prevention, diagnosis, and treatment have been outlined from both an antimicrobial and surgical perspective. A number of these strategies are emerging and require further research to demonstrate efficacy before implementation into clinical guidelines.

Adverse clinical outcomes associated with infections by Enterobacterales producing ESBL (ESBL-E): a systematic review and meta-analysis.

OBJECTIVES: Enterobacterales producing ESBL (ESBL-E) have been notable for their rapid expansion in community settings. This systematic review and meta-analysis aimed to summarize evidence investigating the association between ESBL-E infection and adverse clinical outcomes, defined as bacteraemia, sepsis or septic shock, and all-cause mortality in adult patients. METHODS: Database search was conducted in PubMed, Scopus and EMBASE. In general, studies were screened for effect estimates of ESBL-E colonization or infection on clinical outcomes with non-ESBL-producing Enterobacterales as comparator, adult populations and molecular ascertainment of ESBL gene. Meta-analysis was performed using the inverse variance heterogeneity model. RESULTS: Eighteen studies were identified, including 1399 ESBL-E and 3200 non-ESBL-E infected patients. Sixteen of these studies included only bacteraemic patients. Mortality was studied in 17 studies and ESBL-E infection was significantly associated with higher odds of mortality compared with non-ESBL-producing Enterobacterales infection (OR = 1.70, 95% CI: 1.15-2.49, I 2=58.3%). However, statistical significance did not persist when adjusted estimates were pooled (aOR = 1.67, 95% CI: 0.52-5.39, I 2=78.1%). Septic shock was studied in seven studies and all included only bacteraemic patients. No association between ESBL-E infection and shock was found (OR = 1.23, 95% CI: 0.75-2.02, I 2=14.8%). Only one study investigated the association between ESBL-E infection and bacteraemia. CONCLUSIONS: Infections by ESBL-E appear to be significantly associated with mortality but not septic shock. Available studies investigating bacteraemia and shock as an intermediate outcome of ESBL-E infections are lacking. Future studies investigating the relationship between clinical outcomes and molecular characteristics of resistant strains are further warranted, along with studies investigating this in non-bacteraemic patients.

Is Ceftazidime/Avibactam an Option for Serious Infections Due to Extended-Spectrum-ß-Lactamase- and AmpC-Producing Enterobacterales?: a Systematic Review and Meta-analysis.

Carbapenem-sparing regimens are needed for the treatment of infections caused by extended-spectrum-ß-lactamase (ESBL)- and AmpC-producing members of the Enterobacterales We sought to compare the clinical efficacy of ceftazidime/avibactam and carbapenems against ESBL- and AmpC-producing Enterobacterales species. A systematic review and meta-analysis of randomized controlled trials comparing ceftazidime/avibactam with carbapenems for the treatment of ESBL- and AmpC-producing Enterobacterales was conducted. Five randomized controlled trials (RCTs) with ESBL- and AmpC-specific outcome data were compiled. Of the 246 patients infected with an ESBL-producing microorganism in the ceftazidime/avibactam arm, 224 (91%) had a clinical response at test of cure (TOC), versus 240 of 271 (89%) patients in the carbapenem arm (risk ratio [RR], 1.02; 95% confidence interval [CI], 0.97 to 1.08; P = 0.45; I2 = 0%). Clinical response rates for AmpC producers in the ceftazidime/avibactam and carbapenem arms were 32/40 (80%) and 37/42 (88%), respectively (RR, 0.91; 95% CI, 0.76 to 1.10; P = 0.35; I2 = 0%). Microbiological response and mortality rates were not reported specifically for ESBL/AmpC producers. Ceftazidime/avibactam may be a carbapenem-sparing option for the treatment of mild to moderate complicated urinary tract and intra-abdominal infections caused by ESBL-producing Enterobacterales species, and the data are too limited to provide any conclusive recommendations for the AmpC producers. Care should be taken before extrapolating this to severe infections, given that the representation of this population in the reviewed studies was negligible. Ceftazidime/avibactam is a costly drug active against carbapenem-resistant microorganisms and should be used judiciously to preserve its activity against them.