Treatment Of Complicated Intra-abdominal Infections Research Articles

Successful treatment of complicated intra-abdominal infection with 13 gastrointestinal leaks:a case report

Successful treatment of complicated intra-abdominal infection with 13 gastrointestinal leaks:a case report

Neonatal complicated intraabdominal infection.

The purpose of this review is to summarize the treatment of complicated intraabdominal infections (cIAIs) in premature infants. Recent work has continued to define the complex nature of cIAIs and necrotizing enterocolitis (NEC). This includes new findings on the microbiome, breast milk and risk factors associated with NEC. The treatment of cIAIs employs a combination of both surgical and medical treatment. Further look at what type and timing of surgical intervention is used as well as the ideal antibiotic regimen. Upcoming research is highlighted in future directions of NEC treatment. cIAIs in premature infants is a challenging disease with more research needed to further delineate the pathophysiology and treatment options.

Intra-abdominal infection after tumor surgery: tigecycline combined with β-lactam antibiotics versus tigecycline alone

BackgroundsTigecycline has a broad spectrum of antimicrobial activity and has been approved for the treatment of complicated intra-abdominal infections. However, it is debatable whether tigecycline should be used alone or in combination. This study aimed to investigate whether tigecycline plus β-lactam antibiotics (combination therapy [CT] group) are superior to tigecycline alone (monotherapy [MT] group) in non-critically ill intra-abdominal infection patients after tumor surgery.MethodsThis was a multicenter, retrospective cohort study. The primary outcome was mortality during the hospital stay. Secondary outcomes were clinical success rate, microbial eradication rate, relapse rate within one week, course of treatment, and adverse effects. Propensity score matching (PSM) was used to adjust the degree of infection before medication between the MT and CT groups. Univariate comparisons were performed using the chi-squared test for qualitative variables and Student’s t-test or the Mann-Whitney U-test for continuous variables, as appropriate. Multivariate logistic regression analysis was performed to examine the relationship between antimicrobial treatments and mortality during hospitalization. The paired samples Wilcoxon test was used to compare the parameters before and after medication.ResultsIn total, 291 patients were included in the final analysis: 128 in MT group and 163 in CT group. Mortality rate was 6.25% in the MT group and 6.13% in the CT group (P = 0.97). Multivariate logistic regression model showed that carbapenem-resistant organisms (OR: 4.35, 95% CI: 2.36 ~ 61.70) and age > 65 (OR: 1.32, 95% CI:1.19 ~ 3.01) were independent risk factors for death. CT group had a shorter defervescence time (P < 0.05), with less likelihood of relapse (P < 0.05) but had a more significant effect on activated partial thromboplastin and prothrombin time.ConclusionsTigecycline plus β-lactam wasn’t superior to tigecycline monotherapy for the treatment of non-critically ill patients with intra-abdominal infection. But for advanced age patients with cancer, tigecycline combination therapy maybe a better choice in terms of mortality.

Efficacy, safety, and tolerability of antimicrobial agents for complicated intra-abdominal infection: a systematic review and network meta-analysis

BackgroundWhich antimicrobial agents provide the optimal efficacy, safety, and tolerability for the empirical treatment of complicated intra-abdominal infection (cIAI) remains unclear but is paramount in the context of evolving antimicrobial resistance. Therefore, updated meta-analyses on this issue are warranted.MethodsWe systematically searched four major electronic databases from their inception through October 2022. Randomized controlled trials examining antimicrobial agents for cIAI treatment were included. Two reviewers independently assessed the quality of included studies utilizing the Cochrane Collaboration’s risk of bias tool as described in the updated version 1 of the Cochrane Collaboration Handbook and extracted data from all manuscripts according to a predetermined list of topics. All meta-analyses were conducted using R software. The primary outcome was clinical success rate in patients with cIAIs.ResultsForty-five active-controlled trials with low to medium methodological quality and involving 14,267 adults with cIAIs were included in the network meta-analyses. The vast majority of patients with an acute physiology and chronic health evaluation II score < 10 had low risk of treatment failure or death. Twenty-one regimens were investigated. In the network meta-analyses, cefepime plus metronidazole was more effective than tigecycline and ceftolozane/tazobactam plus metronidazole (odds ratio [OR] = 1.96, 95% credibility interval [CrI] 1.05 ~ 3.79; OR = 3.09, 95% CrI 1.02 ~ 9.79, respectively). No statistically significant differences were found among antimicrobial agents regarding microbiological success rates. Cefepime plus metronidazole had lower risk of all-cause mortality than tigecycline (OR = 0.22, 95% CrI 0.05 ~ 0.85). Statistically significant trends were observed favoring cefotaxime plus metronidazole, which exhibited fewer discontinuations because of adverse events (AEs) when compared with eravacycline, meropenem and ceftolozane/tazobactam plus metronidazole (OR = 0.0, 95% CrI 0.0 ~ 0.8; OR = 0.0, 95% CrI 0.0 ~ 0.7; OR = 0.0, 95% CrI 0.0 ~ 0.64, respectively). Compared with tigecycline, eravacycline was associated with fewer discontinuations because of AEs (OR = 0.17, 95% CrI 0.03 ~ 0.81). Compared with meropenem, ceftazidime/avibactam plus metronidazole had a higher rate of discontinuation due to AEs (OR = 2.09, 95% CrI 1.0 ~ 4.41). In pairwise meta-analyses, compared with ceftriaxone plus metronidazole, ertapenem and moxifloxacin (one trial, OR = 1.93, 95% CI 1.06 ~ 3.50; one trial, OR = 4.24, 95% CI 1.18 ~ 15.28, respectively) were associated with significantly increased risks of serious AEs. Compared with imipenem/cilastatin, tigecycline (four trials, OR = 1.57, 95%CI 1.07 ~ 2.32) was associated with a significantly increased risk of serious AEs. According to the surface under the cumulative ranking curve, Cefepime plus metronidazole was more likely to be optimal among all treatments in terms of efficacy and safety, tigecycline was more likely to be worst regimen in terms of tolerability, and eravacycline was more likely to be best tolerated.ConclusionThis study suggests that cefepime plus metronidazole is optimal for empirical treatment of patients with cIAIs and that tigecycline should be prescribed cautiously considering the safety and tolerability concerns. However, it should be noted that data currently available on the effectiveness, safety, and tolerability of antimicrobial agents pertain mostly to lower-risk patients with cIAIs.

A Real-world Multicenter Outpatient Experience of Ceftolozane/Tazobactam.

Ceftolozane/tazobactam (C/T) is indicated for the treatment of complicated intra-abdominal infection (IAI), complicated urinary tract infection (UTI), and hospital-acquired/ventilator-associated bacterial pneumonia caused by susceptible bacteria. As real-world data are limited, we report utilization and associated outcomes of C/T use in the outpatient setting. This is a multicenter, retrospective study of patients who received C/T between May 2015 and December 2020. Demographics, infection types, C/T utilization characteristics, microbiology, and health care resource utilization were collected. Clinical success was defined as complete or partial symptom resolution at completion of C/T. Persistent infection and discontinuation of C/T were deemed nonsuccess. Logistic regression analysis was used to identify predictors associated with clinical outcomes. A total of 126 patients (median age, 59 years; 59% male; median Charlson index, 5) from 33 office infusion centers were identified. Infection types included 27% bone and joint infection (BJI), 23% UTI, 18% respiratory tract infection (RTI), 16% IAI, 13% complicated skin and soft tissue infection (cSSTI), and 3% bacteremia. The median daily dose of C/T was 4.5 g, primarily administered via elastomeric pumps as intermittent infusion. The most common gram-negative pathogen was P. aeruginosa (63%), 66% of which was multidrug-resistant and 45% carbapenem-resistant. Enterobacterales was identified in 26% of isolates, of which 44% were extended-spectrum beta-lactamase producers. The overall clinical success rate of C/T was 84.7%. Nonsuccessful outcomes were due to persistent infections (9.7%) and drug discontinuations (5.6%). C/T was successfully used in the outpatient setting to treat a variety of serious infections with a high prevalence of resistant pathogens.

Carbapenem Antibiotics Versus Other Antibiotics for Complicated Intra-abdominal Infections: a Systematic Review and Patient-Level Meta-analysis of Randomized Controlled Trials (PROSPERO CRD42018108854)

BackgroundThe treatment of complicated intra-abdominal infections remains a challenge. Both optimal medical and surgical therapy (i.e., source control) are needed to achieve low mortality and morbidity. The objective of this systematic review and meta-analysis is to determine the impact of carbapenem antibiotic therapy compared to other antibiotics in complicated intra-abdominal infections (secondary peritonitis) with an emphasis on mortality and postoperative complications. MethodsA systematic literature search from PubMed/Medline and Web of Science databases was carried out. The last search was conducted in August 2022. PRISMA guidelines were followed. Pre-defined outcomes were mortality, treatment success, treatment failure, and adverse events. ResultsTen randomized controlled trials, published from 1983 to 2013 with a total of 2377 patients (1255 patients in the carbapenem antibiotics group and 1122 in the control group), were identified. A meta-analysis comparing patients undergoing carbapenem antibiotic therapy and patients receiving other antibiotics was performed. No significant difference regarding mortality (OR 1.19, 95% CI [0.79; 1.82], p = 0.40), treatment success (OR 1.17, 95% CI [0.72; 1.91], p = 0.53), and treatment failure (OR 0.84, 95% CI [0.48; 1.45], p = 0.52) was observed. Carbapenem therapy was associated with fewer adverse events compared to therapy with other antibiotics (OR 0.79, 95% CI [0.65; 0.97], p = 0.022). ConclusionThere is currently no evidence that carbapenem antibiotics are superior in terms of mortality, and success or failure for the treatment of complicated intra-abdominal infections (secondary peritonitis). The rate of adverse events is lower under carbapenem therapy compared to control antibiotics. Trial RegistrationPROSPERO 2018 CRD42018108854.

Multicenter Clinical Evaluation of ETEST Eravacycline for Susceptibility Testing of Enterobacteriaceae and Enterococci.

Eravacycline (ERV) (brand name Xerava [Tetraphase]) is a new tetracycline-class antibacterial that has been approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for treatment of complicated intra-abdominal infections (cIAIs). ETEST is a gradient diffusion method that represents a simple alternative to the broth microdilution (BMD) method for performing antimicrobial susceptibility testing (AST). A multicenter evaluation of the performance of the new ETEST ERV (bioMérieux) in comparison with BMD was conducted following FDA and International Standards Organization (ISO) recommendations, using FDA- and EUCAST-defined breakpoints. Clinical isolates of Enterobacteriaceae (n = 542) and Enterococcus spp. (n = 137) were included. Based on the BMD reference method, 92 Enterobacteriaceae isolates and 9 enterococcal isolates were nonsusceptible to ERV according to the FDA breakpoints, while 7 Escherichia coli isolates and 3 Enterococcus sp. isolates were classified as ERV resistant according the EUCAST breakpoints. Referring to FDA performance criteria, the ETEST ERV demonstrated 99.4% and 100.0% essential agreement (EA), 98.0% and 94.9% categorical agreement (CA), very major error (VME) rates of 5.4% and 33.33%, and major error (ME) rates of 1.3% and 3.1% with clinical and challenge isolates, respectively, of Enterobacteriaceae and Enterococcus spp. According to EUCAST breakpoints, E. coli and Enterococcus sp. isolate results also met ISO acceptance criteria for EA and CA (EA of 99.0% and 100.0%, respectively, and CA of 100.0% for both), without any VMEs or MEs. In conclusion, we report that ETEST ERV represents an accurate tool for performing ERV AST of Enterobacteriaceae and Enterococcus sp. isolates.

Cost-effectiveness of ceftazidime/avibactam plus metronidazole versus meropenem as first-line empiric therapy for the treatment of complicated intra-abdominal infections: A study based on the in-vitro surveillance data in China

BackgroundWith the increase in drug resistance rates of pathogens isolated from complicated intra-abdominal infections (cIAIs), ceftazidime/avibactam (CAZ-AVI) is increasingly used clinically. However, given the high drug cost and the fact that not yet covered by the health insurance payment, this study evaluated the cost-effectiveness of CAZ-AVI plus metronidazole versus meropenem as a first-line empiric treatment for cIAIs from the perspective of the Chinese healthcare system. MethodsA decision analytic model with a one-year time horizon was constructed to assess the cost-effectiveness based on the entire disease course. Model inputs were mainly obtained from clinical studies, published literature, and publicly available databases. Primary outcomes were cost, quality-adjusted life years (QALYs), life years (Lys), and incremental cost-effectiveness ratio (ICER). One-way sensitivity analysis and probabilistic sensitivity analysis were also performed. ResultsIn the base cases, compared to meropenem, CAZ-AVI plus metronidazole had a shorter mean hospital length of stay (–0.77 days per patient) and longer life expectancy (+0.05 LYs and +0.06 QALYs). CAZ-AVI plus metronidazole had an ICER of $25517/QALY, which is well below the threshold of $31509 per QALY in China. The one-way sensitivity analysis showed that the change of the treatment duration of CAZ-AVI plus metronidazole was the parameter that most influenced the results of the ICER. In probabilistic sensitivity analysis, CAZ-AVI plus metronidazole was the optimal strategy in 75% of simulations at $31510/QALY threshold. ConclusionsCAZ-AVI plus metronidazole could be considered as a cost-effective option for the empiric treatment of patients with cIAIs in China, and this benefit will be more evident when the price of CAZ-AVI decreases by 23.8%.

1679. Susceptibility of Gram-Negative Clinical Isolates Collected from the USA in 2020 to Eravacycline and Comparators

Abstract Background Eravacycline is a fully-synthetic, fluorocycline antibacterial approved by the FDA and EMA for the treatment of complicated intra-abdominal infections (cIAI) in patients ≥18 years of age. The activity of eravacycline has been surveyed annually since 2013. Here we present data on the in vitro activity of eravacycline and comparators against Gram-negative pathogens isolated in the USA during 2020. Methods Isolates were collected from patients from various body sites. Minimum inhibitory concentrations (MICs) were determined by CLSI broth microdilution. Antibiotic susceptibility was determined using current CLSI breakpoints, except for eravacycline and tigecycline where FDA and EUCAST breakpoints were used due to a lack of CLSI breakpoints. Multi-drug resistant (MDR) was defined as resistance to ≥3 antibiotics including aztreonam, a carbapenem (meropenem or ertapenem), third or fourth generation cephalosporin (cefepime,cefotaxime,ceftazidime, or ceftriaxone), gentamicin, levofloxacin, piperacillin/tazobactam, tetracycline or tigecycline. Results Summary MIC and susceptibility data for eravacycline and select comparators are shown in the Table. Eravacycline MIC90 against Enterobacterales combined was 0.5 μg/mL (MDR Enterobacterales and individual species ranged from 0.25 to 1 μg/mL) and susceptibility was 93.9% using both FDA and EUCAST breakpoints. Tigecycline MIC90 against Enterobacterales was 1 μg/mL and susceptibility using FDA breakpoints (set in 2005) was 96.8%, whereas susceptibility by EUCAST breakpoints (set in 2019) was 87.8%. Eravacycline MIC50 and MIC90 against A. baumannii was 0.5 and 2 μg/mL, respectively; being at least 4-fold lower than that observed for tigecycline. Conclusion Eravacycline in vitro activity has remained unchanged since 2013, with comparable annual susceptibility rates observed against clinically important Gram-negative pathogens. These data also highlight that FDA breakpoints for tigecycline against Enterobacterales need urgent review to avoid potential false reporting of tigecycline susceptibility. In contrast, eravacycline FDA breakpoints are in keeping with those published by EUCAST and can be used to predict the clinical outcome of eravacycline treatment. Disclosures Tony Hodges, MD, LaJolla Pharmaceutical: Chief Medical Officer|LaJolla Pharmaceutical: Stocks/Bonds.

A phase III, multicenter, double-blind, randomized clinical trial to evaluate the efficacy and safety of ceftolozane/tazobactam plus metronidazole versus meropenem in Chinese participants with complicated intra-abdominal infections

This study aimed to evaluate the efficacy and safety of ceftolozane/tazobactam (C/T) plus metronidazole versus meropenem plus placebo for the treatment of complicated intra-abdominal infection (cIAI) in Chinese adult participants. In this phase III clinical trial (NCT03830333), Chinese adult participants with cIAI were randomized 1:1 to receive C/T plus metronidazole or meropenem plus placebo. The primary objective was to assess C/T plus metronidazole for noninferiority versus meropenem for clinical response rate at the test of cure (TOC; 28 ± 2 days after study start) visit in the clinically evaluable population. Secondary endpoints included clinical and microbiologic responses at the TOC and end-of-treatment (≤24 hours after last dose) visits and adverse event rates. Clinical cure at the TOC visit in the clinically evaluable population was 95.2% and 93.1% for C/T plus metronidazole and meropenem, respectively (between-treatment difference: 2.1% [95% confidence interval: -4.7%, 8.8%]); thus, noninferiority was met. Clinical responses at the TOC and end-of-treatment visits and microbiologic responses at the TOC visit were consistent with the primary efficacy endpoint. Safety was comparable between study treatment groups. In Chinese adult participants with cIAI, C/T plus metronidazole was noninferior to meropenem, with comparable safety.

EE236 Cost-Effectiveness of Ceftazidime/Avibactam Versus Meropenem in the Treatment of Complicated Intra-Abdominal Infections in China

EE236 Cost-Effectiveness of Ceftazidime/Avibactam Versus Meropenem in the Treatment of Complicated Intra-Abdominal Infections in China

POSA122 Budget Impact Analysis of Introducing Ceftolozane/Tazobactam Injection for Treatment of Complicated Intra-Abdominal Infections and Complicated Urinary Tract Infections in the Ministry of Health Malaysia Facilities

Growing prevalence of multidrug-resistant (MDR) pathogens is a major problem specifically in cases of complicated intra-abdominal infections (cIAIs) and complicated urinary tract infections (cUTIs) associated with increasing mortality, morbidity and healthcare costs leading to the need of new effective and safe treatment options. The aim of this study is to estimate the budget impact (BI) of introducing Ceftolozane/Tazobactam as treatment of cIAIs and cUTIs in public facilities under Ministry of Health Malaysia (MoHM).

1243. Eravacycline in Bacteremia: A Case Series

BackgroundEravacycline (ERV) is FDA-approved for the treatment of complicated intra-abdominal infections, but there is limited experience for non-FDA approved indications. MethodsWe present five cases that utilized ERV for treatment of bacteremia.ResultsPatient 1 in septic shock (SS) started on vancomycin (VAN) and ceftazidime-avibactam (CZA). Blood culture (BC) finalized to E. coli and regimen narrowed to CZA. On day 9, gram-positive cocci in chains in BC grew and VAN was added. BC finalized to VRE faecium and regimen was modified to ERV on day 12. Repeat BC on day 15 finalized to no growth with no recurrence of bacteremia until discharged (day 78). Patient 2 treated for MSSA bacteremia with cefazolin and subsequent K. pneumoniae VAP treated with ceftriaxone (CRO) (day 18-26). On day 27, meropenem (MEM) was initiated for gram-negative bacteremia and started on IV trimethoprim/sulfamethoxazole (TMP/SMX) the following day for pneumonia caused by TMP/SMX-susceptible S. maltophila. BC finalized on day 29 to S. maltophila resistant to TMP/SMX, regimen modified to ERV. Repeat BC on day 30 finalized to no growth and ERV was continued until day 42 with no recurrence of bacteremia; however, patient died on day 45. Patient 3 with renal failure and on day 11, CRO started for SBP prophylaxis. On day 13, switched to daptomycin and cefepime (FEP) as patient was febrile and BC repeated. BC finalized to VRE faecium and was started on ERV on day 17 and completed a 7-day course with no recurrence of bacteremia; however, patient died on day 34. Patient 4 initially treated for bacterial superinfection with CRO and azithromycin, and subsequent worsening pneumonia treated with VAN and MEM (day 10-17). On day 19, patient was febrile and treated with VAN and FEP until day 27. Repeat BC on day 29 finalized to VRE species and modified to ERV on day 32. ERV continued for a 7-day course and was discharged with no repeat BC obtained to confirm clearance. Patient 5 in SS started on VAN and MEM. On day 3, BC on admission finalized to VRE faecium and therapy switched to ERV. Repeat BC taken on day 3 after ERV initiation were negative. Discharged to complete two-week course of ERV.ConclusionERV may be an option for bacteremia as demonstrated by clearance in four of five cases. More studies must be conducted as these reports show variable clinical outcomes.Disclosures Joshua R. Rosenberg, MD, Allergan/Abbvie (Consultant)La Jolla/Tetraphase (Consultant)Melinta (Consultant)Merck (Consultant)Paratek (Consultant)Sanofi (Consultant)Shionogi (Consultant)

1288. Evaluation of Predictors for Clinical Success in Patients Treated with Eravacycline for Various Infections

Abstract Background Eravacycline (ERV) is approved in the United States (US) for the treatment of complicated intra-abdominal infections in adults. We aimed to evaluate the independent predictors of clinical success in patients treated with ERV for various infections. Methods Multicenter, retrospective, observational study conducted from September, 2018 to April, 2021. We included adults treated with ERV for ≥ 72hours. Clinical success was defined as 30-day survival, lack of 30-day infection-recurrence, and resolution of infection signs/symptoms. All outcomes were measured from ERV initiation. Multivariable logistic regression (MLR) was performed to identify independent predictors of clinical success. Clinically relevant variables were selected for model entry based on bivariate comparisons (P&amp;lt; 0.2) in a backward fashion. Results We included 223 patients from 16 medical centers in 13 geographically unique states. The median (IQR) age was 61 (50-69) years, 57% were male and 62% were Caucasian. Median (IQR) APACHE II, and Charlson Comorbidity scores were 15 (10-21), and 3 (1-5), respectively. Sources of infection were primarily intra-abdominal (27%) and respiratory (27%). Common pathogens included Acinetobacter baumannii (21%) and those of the Enterobacterales order (36%). Infectious diseases consultation and surgical interventions were obtained in 93.7% and 52% respectively. Clinical success occurred in 64%, specifically 30-day survival in 78%, absence of 30-day infection-recurrence in 93%, and 74% experienced resolution of infection signs/symptoms. Since characteristics and outcomes were similar among various pathogens, MLR was conducted using the overall cohort. Skin as a source and combination therapy with ERV were independently associated with higher clinical success: odds ratio 3.3 [CI 1.1-10.2] and 2.9 [1.4-5.9], respectively. Whereas, ICU admission at culture time and undergoing surgery within 30 days of culture were independently associated with reduced odds of clinical success: 0.4 [0.17-0.80] and 0.3 [0.11-0.63] respectively. Conclusion Although most ERV treated patients experienced clinical success, factors independently associated with higher clinical success are crucial to consider for optimum antibiotic selection. Disclosures Kimberly C. Claeys, PharmD, GenMark (Speaker’s Bureau) Madeline King, PharmD, tetraphase (Speaker’s Bureau) Michael P. Veve, Pharm.D., Cumberland (Grant/Research Support)Paratek Pharmaceuticals (Research Grant or Support) Bruce M. Jones, PharmD, BCPS, Abbvie (Consultant, Advisor or Review Panel member, Speaker’s Bureau)La Jolla (Speaker’s Bureau)Melinta (Consultant)Merck (Consultant)Paratek (Consultant, Speaker’s Bureau) Susan L. Davis, PharmD, Nothing to disclose Michael J. Rybak, PharmD, MPH, PhD, Paratek Pharmaceuticals (Research Grant or Support)

A retrospective, multicentre evaluation of eravacycline utilisation in community and academic hospitals

Eravacycline is a novel, fully-synthetic tetracycline approved by the FDA for treatment of complicated intra-abdominal infections in August 2018. This study sought to characterise early clinical experience with this novel antibiotic. Eravacycline utilisation for 66 patients was retrospectively evaluated. Eravacycline was used as monotherapy in 62.1% of cases. Mean duration of therapy was 13.1 ± 9.9 days. The majority (68.2%) of treatment was for off-label indications, including 34.8% for pulmonary and 28.8% for skin/soft tissue infections. A number of difficult-to-treat organisms were encountered: 50% of identified Gram-negative pathogens were resistant to carbapenems in vitro; and 48% of identified Gram-positive pathogens were resistant to vancomycin in vitro. The patient population had a high illness acuity, with 42.4% requiring ICU admission, 59.1% having ≥2 co-morbidities and 33.3% having ≥3 co-morbidities. Nevertheless, 95.5% experienced clinical improvement, with 86.4% achieving full infection resolution following eravacycline. Three patients who did not experience clinical improvement had an intra-abdominal source of infection without adequate source control. The remaining six who did not experience full infection resolution died from unrelated non-infectious causes during hospital admission. Adverse events were uncommon (4.5%), limited to nausea/vomiting, and not leading to eravacycline discontinuation. Although two patients had a history of Clostridioides difficile infection (CDI), no patients developed CDI while receiving eravacycline. These results illustrate the potential versatility of eravacycline with a broad activity spectrum, good safety and tolerability profile, flexibility for use in patients with renal injury or antibiotic allergies, and positive clinical outcomes in this real-world cohort.

In vitro susceptibility of carbapenem-resistant Enterobacterales to eravacycline – the first report from Croatia

The main obstacle in treatment of infections caused by carbapenem-resistant Enterobacterales (CRE) are limited treatment options. The novel antimicrobial agents other than β-lactams with activity not being dependent on β-lactamase class are especially important. Eravacycline (ERV) is the first fully synthetic fluorocycline indicated for the treatment of complicated intra-abdominal infections in adults. Eighty CRE isolates at the University Hospital Centre Zagreb, Croatia were examined for susceptibility to ERV by disc diffusion method and minimal inhibitory concentration (MIC). Total of 54 (54/80; 67.5%) isolates were susceptible to ERV with MIC50 of ≤0.5 μg/mL and MIC90 of 4 μg/mL. Susceptibility of OXA-48 positive isolates was not significantly higher in comparison with NDM positive (P = 0.539) and VIM positive (P = 0.7805) isolates. ERV is possible alternative to novel β-lactamase inhibitor combinations for treatment of CRE infections with antimicrobial susceptibility testing of CRE isolate to ERV in particular patient as condicio sine qua non before administration.

New Perspectives on Antimicrobial Agents: Ceftolozane-Tazobactam.

Ceftolozane-tazobactam (C/T) is a new fifth-generation cephalosporin/beta-lactamase inhibitor combination approved by the Food and Drug Administration and the European Medicines Agency for treatment of complicated intraabdominal infections, complicated urinary tract infections, and hospital-acquired pneumonia in adult patients. This review will briefly describe the pharmacology of C/T and focus on the emerging clinical trial and real-world data supporting its current utilization. Additionally, our synthesis of these data over time has set our current usage of C/T at Barnes-Jewish Hospital (BJH). C/T is primarily employed as directed monotherapy at BJH when Pseudomonas aeruginosa isolates are identified with resistance to other beta-lactams. C/T can also be used empirically in specific clinical situations at BJH prior to microbiological detection of an antibiotic-resistant P. aeruginosa isolate. These situations include critically ill patients in the intensive care unit (ICU) setting, where there is a high likelihood of infection with multidrug-resistant (MDR) P. aeruginosa; patients failing therapy with a carbapenem; specific patient populations known to be at high risk for infection with MDR P. aeruginosa (e.g., lung transplant and cystic fibrosis patients); and patients know to have previous infection or colonization with MDR P. aeruginosa.

Efficacy and safety of eravacycline: A meta-analysis

ObjectivesThis study was conducted to evaluate the efficacy and safety of eravacycline, a recently approved fluorocycline for treatment of complicated intra-abdominal infections (cIAIs). MethodsPubMed, EMBASE and three trial registries were searched for randomised controlled trials (RCTs) comparing the efficacy and safety of eravacycline versus comparators. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using random-effects models. The study outcomes included clinical response, all-cause mortality and adverse events (AEs). ResultsThree RCTs (1128 patients) with cIAIs were included. There were no significant differences in clinical response in the modified intention-to-treat (ITT) (OR, 0.91, 95% CI 0.62–1.35; I2 = 0%), microbiological ITT (OR, 0.93, 95% CI 0.61–1.41; I2 = 0%) and clinically evaluable (OR, 0.98, 95% CI 0.55–1.75; I2 = 0%) populations or in all-cause mortality (OR, 1.18, 95% CI 0.16–8.94; I2 = 0%). Eravacycline was associated with significantly greater odds of total AEs (OR, 1.55, 95% CI 1.20–1.99; I2 = 0%) and nausea (OR, 5.29, 95% CI 1.77–15.78; I2 = 1.70%) but the increase in vomiting was non-significant (OR, 1.44, 95% CI 0.73–2.86; I2 = 1.70%). There were no significant differences in serious AEs or discontinuation due to AEs. ConclusionThis meta-analysis of RCTs found similar clinical efficacy and mortality for eravacycline compared with carbapenems for treatment of cIAIs. However, the odds of total AEs and specifically nausea was higher with eravacycline, while no significant differences were observed in vomiting (although numerically higher), serious AEs or discontinuation due to AEs.

A randomized controlled trial comparing the efficacy of tigecycline versus meropenem in the treatment of postoperative complicated intra-abdominal infections

The efficacy and safety of tigecycline in the treatment of complicated intra-abdominal infections (cIAIs) is potentially controversial. Here we conducted the non-inferiority study to assess the efficacy and safety of tigecycline versus meropenem in the treatment of postoperative cIAIs. Data of abdominal tumor surgery patients with postoperative cIAIs admitted to intensive care unit (ICU) between October 2017 and December 2019 were collected. A prospective, randomized controlled trial was conducted in which 56 eligible patients with cIAIs randomly received intravenous tigecycline or meropenem for 3 to 14 days. Patients and clinicians were not blinded to the group allocation. The total of 56 patients were enrolled, which were divided into 2 groups, one group included 30 patients receiving meropenem and another group included 26 receiving tigecycline therapy. The 2 groups were similar at demographic and baseline clinical characteristics. Microorganisms were isolated from 46 of 56 patients (82.14%), with a total of 107 pathogens were cultured in two groups. The two groups had similar distribution of infecting microorganisms. The primary end point was the clinical response at the end-oftherapy (EOT) visit and upon discharge visit and comprehensive efficacy. The clinical success rates were 83.33%, 76.67% for meropenem versus 76.92%, 88.46% for tigecycline at the EOT visit and upon discharge visit (P>0.05), respectively. Comprehensive efficacy did not significantly differ between two groups either. There were no significant differences in 30-day and 60-day all-cause mortality between two groups (P>0.05). The univariable analysis identified that serum albumin at admission ICU, colorectal cancer on oncology type, postoperative abdominal bleeding were the risk factors for 60-day all-cause mortality. The multivariable analysis showed that postoperative abdominal bleeding were independent predictors of 60-day all-cause mortality. Gastrointestinal disorders and antibacterials-induced Fungal Infection were the most frequently reported adverse events (AEs). The incidence of AEs was similar between meropenem and tigecycline groups (P>0.05). Taken together, the study demonstrated that tigecycline is as effective and safe as meropenem for postoperative cIAIs in abdominal tumors patients. Tigecycline is non-inferior to meropenem.

Tigecycline Use in Surgical Intensive Care Unit for the Treatment of Complicated Intra-Abdominal Infections: A Real-World Study

OBJECTIVES: To describe real-world use of tigecycline in cIAIs patients. METHODS: A retrospective, observational study enrolled cIAIs patients hospitalized in The First Affiliated Hospital, Sun Yat-sen University from January 1, 2013 to June 30, 2017 was conducted. Patients’ data were collected and matched based on age, gender, and Acute Physiologic Assessment and Chronic Health Evaluation II (APACHE II) score according to receiving first-line, later-line, or no tigecycline during hospitalization. RESULTS: Data were collected for 52 patients. 82.6% were male. Mean age was 57.8 years and APACHE II score was 14.8. The incidence of both extended-spectrum beta-lactamase producing and carbapenem-resistant pathogens was high on initial culture; however, few patients received first-line tigecycline. No significant difference in mortality rate was identified among first-line, later-line and no tigecycline users. Of surviving patients, shorter hospital length of stay was observed for patients receiving first- vs later-line or no tigecycline, respectively. ICU length-of-stay was shorter in patients receiving first- vs later-line or no tigecycline. CONCLUSIONS: First-line tigecycline use was rare in our surgical intensive care unit. Resistant organisms were commonly cultured from initial specimens. Although these results are limited by small patient numbers and single center, our results suggest that early tigecycline use may have significant benefits with similar mortality. Further research is warranted to demonstrate the values of early tigecycline use in cIAIs patients.