Complicated Intra-abdominal Infections Research Articles

1592. Antimicrobial Activity of Ceftazidime-Avibactam and Comparator Agents Against Enterobacterales and Pseudomonas aeruginosa With Overexpression of AmpC β-Lactamase From Phase 3 Clinical Trials

BackgroundAmpC overproduction is a main mechanism of carbapenem resistance, in the absence of acquired carbapenemases. Ceftazidime-avibactam (CAZ-AVI) has potent in vitro activity against AmpC-producing P. aeruginosa and Enterobacterales that are resistant to carbapenems and other β-lactams.MethodsActivity of CAZ-AVI and comparators was evaluated against AmpC-overproducing Enterobacterales (n=77) and P. aeruginosa (n=53) collected from 4 CAZ-AVI clinical trials: RECLAIM (complicated intra-abdominal infection [cIAI]), REPRISE (cIAI/complicated urinary tract infection [cUTI]), RECAPTURE (cUTI) and REPROVE (hospital-acquired pneumonia/ventilator associated pneumonia). In vitro susceptibility of CAZ-AVI and comparators was performed by broth microdilution using ThermoFisher custom panels. CLSI breakpoints were used to determine susceptibility. Quantitative PCR and microarray data were used to characterize presence and expression of AmpC. Clinical response at test of cure was assessed.ResultsAgainst 77 AmpC-overproducing Enterobacterales isolates, meropenem-vaborbactam (MVB) (98.7% susceptible [S]), CAZ-AVI (96.1% S), and meropenem (MEM) (96.1% S) had similar in vitro activity (Table), with greater in vitro activity than amikacin (AMK) (84.4% S), gentamicin (61.0% S), and ceftolozane-tazobactam (TZC) (35.1% S). Clinical cures in patients with baseline AmpC-overproducing Enterobacterales were 21/26 (81%) in CAZ-AVI group vs 17/20 (85%) in control groups. Against 53 AmpC-overproducing P. aeruginosa isolates, CAZ-AVI (73.6% S) showed greater in vitro activity than AMK (69.8% S), TZC (58.5% S), and MEM (37.7% S). Clinical cures in patients with baseline AmpC-overproducing P. aeruginosa were 12/14 (86%) in CAZ-AVI group vs 9/12 (75%) in control groups. MIC distributions against the same P aeruginosa isolates were CAZ-AVI (MIC50/90, 4/ >64 µg/mL), MVB (MIC50/90, 8/32 µg/mL), and MEM (MIC50/90, 8/32 µg/mL).Table ConclusionCAZ-AVI was the most active agent against AmpC-overproducing P. aeruginosa with higher proportion of clinical cure than controls. CAZ-AVI was also among the most active agents against AmpC-overproducing Enterobacterales, with >96% isolates susceptible.DisclosuresLynn-Yao Lin, MS, AbbVie (Employee) Dmitri Debabov, PhD, AbbVie (Employee) William Chang, BS, AbbVie (Employee) Urania Rappo, MD, MS, PharmD, Allergan (before its acquisition by AbbVie) (Employee)

1587. Activity of Ceftolozane/Tazobactam against Gram-Negative Isolates from Lower Respiratory Tract Infections – SMART United States 2018

BackgroundCeftolozane/tazobactam (C/T) is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor. C/T has been approved by the FDA and EMA for complicated urinary tract infections, complicated intraabdominal infections, and hospital-acquired and ventilator-associated bacterial pneumonia. Using isolates collected in the United States as part of the global SMART surveillance program, we evaluated the activity of C/T and comparators against gram-negative pathogens collected from patients with lower respiratory tract infections (LRTI).MethodsIn 2018, 24 hospitals in the US each collected up to 100 consecutive aerobic or facultative gram-negative bacilli (GNB) from LRTI for a total of 1773 isolates. MICs were determined using CLSI broth microdilution and breakpoints. C/T-nonsusceptible (NS) Enterobacterales and P. aeruginosa isolates were screened by PCR and sequencing for genes encoding β-lactamases.ResultsThe 3 most common species collected from LRTI were P. aeruginosa (35.0% of all collected GNB), K. pneumoniae (10.4%), and E. coli (9.6%). Enterobacterales and P. aeruginosa combined comprised 86.3% of all collected LRTI GNB. The activity of C/T and comparators against GNB from LRTI is shown in the table.C/T was active against 93% of Enterobacterales isolates from LRTI (activity only exceeded by meropenem and amikacin), as well as against 97% of P. aeruginosa and 94% of all Enterobacterales and P. aeruginosa combined (activity only exceeded by amikacin). C/T maintained activity against 69-83% of β-lactam-NS subsets of Enterobacterales and P. aeruginosa combined.Among 67 molecularly characterized C/T-NS Enterobacterales isolates, 19.4% carried KPC, 1.5% acquired AmpC, and 16.4% only extended-spectrum β-lactamases. No acquired β-lactamases were detected in the remaining 62.7% of isolates, of which 92.9% were species with intrinsic AmpC. Among 21 molecularly characterized C/T-NS P. aeruginosa, one isolate carried an IMP-type metallo-β-lactamase, and in the remaining isolates no acquired β-lactamases were detected.Table ConclusionWith its broad coverage of Enterobacterales and P. aeruginosa, C/T can provide an important empiric therapy option for patients with LRTI in the US.DisclosuresSibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Daryl DePestel, PharmD, BCPS-ID, Merck & Co, Inc (Employee) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co, Inc (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)

1596. Ceftolozane/tazobactam (Zerbaxa) for the Treatment of Pseudomonas aeruginosa (PSA) Bacteremia: A Systematic Literature Review (SLR)

BackgroundBacteremia is a significant cause of morbidity and mortality. Several studies have shown this burden to increase among patients with multidrug resistant (MDR) PSA, and in those treated with inappropriate empiric therapy. Ceftolozane/tazobactam (C/T) is a combination of a novel antipseudomonal cephalosporin and an established β-lactamase inhibitor approved for the treatment of complicated urinary tract infection, complicated intra-abdominal infection and hospital-acquired and ventilator-associated bacterial pneumonia. In the absence of specific bacteremia clinical trial data; the aim of this study is to describe all published evidence relating to C/T for the treatment of Gram negative bacteremia.MethodsThis SLR includes all published evidence from December 2015 to March 2020 searched via the OVID platform: EMBASE, MEDLINE, and MEDLINE In-Process. In addition, data published (2018-2019) from the European Society of Clinical Microbiology and Infectious Diseases and Infectious Disease Week Congresses were included. Eligible publications were on adult patients treated with C/T reporting any clinical outcome where data were reported specifically for the bacteremia population.ResultsThe SLR identified 1,455 citations, of which 24 publications representing 23 unique studies met eligibility criteria. This included primary and secondary bacteremia. Ten studies included patients with primary bacteremia, only 7 of which reported results specific to primary bacteremia patients. Despite heterogeneity in study design, patient and treatment characteristics, and a lack of detailed reporting; the majority of studies focused on MDR/ extensively drug resistant (XDR) infections (range: 68.3%-100%). Clinical success/ cure ranged from 33%-100%, with 6/7 studies at >85%; 30-day mortality from 0%-67%, with 3/7 studies at 0% (Table 1).Table 1. Clinical Outcomes reported among Primary Bacteremia population(s) ConclusionAlthough the number of C/T treated patients was small, favorable clinical outcomes were observed, even among highly resistant PSA infections. Heterogeneity was ubiquitous, with diverse and complex patient profiles identified. Further studies where outcomes are stratified by bacteremia status and by timing of C/T treatment are needed.DisclosuresRyan J. Dillon, MSc, Merck & Co., Inc., (Employee) Carisa De Anda, PharMD, Merck & Co Inc, (Employee) Christopher Bruno, MD, Merck & Co., Inc. (Employee) Laura A. Puzniak, PhD, Merck (Employee)

76. Optimizing Clinical Outcomes in Geriatric Patients through a Multidisciplinary Hospital Antimicrobial Stewardship Program

BackgroundAntimicrobial Stewardship Programs (ASP) aim to ensure the appropriate use of antibiotics. There is limited literature evaluating ASP outcomes in hospitalized geriatric patients who are at higher risk for developing Clostridium difficile infection (CDI) or other adverse outcomes. The primary objective of this study was to determine if ASP efforts in this age group decreases the rate of 30-day hospital readmissions due to reinfection or development of CDI, hospital length of stay (LOS) and mortality.MethodsA retrospective chart review was performed to compare the rates of 30-day hospital readmissions because of reinfection or development of CDI in patients 65 years and older who received ASP interventions between January and June 2017. A control group of patients 65 years and older who received antibiotics between January and June 2015 (pre-ASP) was analyzed for comparison. We also assessed their mortality rate and LOS. Patients were included if they received antibiotics for pneumonia (PNA), urinary tract infection (UTI), acute bacterial skin and skin structure infection (ABSSSI) and complicated intra-abdominal infection (cIAI). The ASP team consisted of an infectious diseases physician and a clinical pharmacist who met daily to review patients on broad spectrum antibiotics. ASP interventions consisted of de-escalation of empiric or definitive therapy, change in duration of therapy or discontinuation of therapy.ResultsOverall, 834 patients (540 control; 294 intervention) were included. The 30-day hospital readmission rate for all infection types decreased during the intervention period (19.6% vs 4.8%, P=0.0001). Both the development of CDI during hospital stay and 30-day readmission due to CDI during the intervention period decreased (2.6% vs 0.34%, P=0.019). There was no statistically significant decrease in 30-day hospital readmissions in the PNA (58.5% vs. 35.7%, P=0.11), UTI (18.9% vs. 35.7%, P=0.15), ABSSSI (12.3% vs. 21.4%, P=0.34) or cIAI (10.4% vs 7.1%, P=0.14) arms. There was no statically significant change in LOS (7.50 days vs 7.26 days, P=0.48) or mortality (9.6% vs 6.5%, P=0.12).ConclusionMultidisciplinary ASP efforts significantly reduced 30-day hospital readmission rates and development of CDI in hospitalized patients 65 years and older.Disclosures All Authors: No reported disclosures

1582. In Vitro Activity of Ceftolozane/Tazobactam against Enterobacterales and Pseudomonas aeruginosa Isolates from Geriatric Patients in the Asia/Pacific region – SMART 2016-2018

BackgroundCeftolozane/tazobactam (C/T) is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor approved by FDA and EMA for complicated urinary tract and intraabdominal infections, and hospital-acquired and ventilator-associated bacterial pneumonia. We evaluated the activity of C/T against isolates collected from patients ≥65 years old as part of the SMART surveillance program in Asia/Pacific.MethodsIn 2016-2018, 49 clinical laboratories in Australia, Hong Kong, Malaysia, New Zealand, Philippines, Singapore, Korea, Taiwan, Thailand, and Vietnam each collected up to 250 consecutive gram-negative pathogens per year. Susceptibility was determined using CLSI broth microdilution and breakpoints. C/T-nonsusceptible (NS) Enterobacterales (ENT) and P. aeruginosa (PA) isolates were screened by PCR and sequenced for genes encoding β-lactamases (except ENT from 1 site in Taiwan).Results2082 PA (68.3% lower respiratory tract, 12.7% intraabdominal, 15.1% urinary tract, and 3.0% bloodstream infection isolates) and 8181 ENT isolates (29.8%, 27.8%, 32.5%, and 9.2%, respectively) were collected from patients ≥65 years old. In vitro susceptibility of PA and ENT stratified by length of hospital stay at time of specimen collection (LOS) is shown (Table).C/T maintained activity against 75.5% of 518 P/T-NS, 67.9% of 395 cefepime-NS, and 71.6% of 377 meropenem-NS PA isolates. Among 136 C/T-NS PA isolates, 44.9% carried metallo-β-lactamases (MBL), 0.7% KPC, 1.5% GES carbapenemases, 5.9% only ESBL, and in 47.1% no acquired β-lactamases were detected. Among 878 characterized C/T-NS ENT, 14.1% carried MBL, 5.2% KPC, 3.3% OXA-48-like carbapenemases, and 53.5% AmpC and/or ESBL; no acquired β-lactamases were detected in 23.8% of isolates, of which 89.5% were species with intrinsic AmpC.Table ConclusionSusceptibility of PA and ENT to all studied agents was lower for isolates collected ≥48 than < 48 hours post-admission. C/T was active against >92% of PA in both strata, 7-29 percentage points higher than the studied comparators except amikacin, and against >84% of ENT, 4-30% higher than the comparators except meropenem and amikacin. C/T is a potential new treatment option for older patients with infections caused by ENT and PA in Asia/Pacific.DisclosuresSibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Wei-Ting Chen, MD, Merck, Sharp & Dohme, Taiwan (Employee) Yivonne Khoo, PhD, Merck, Sharp & Dohme, Malaysia (Employee) Kanchan Balwani, MBBS, MS, Merck, Sharp & Dohme, Hong Kong (Employee) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co, Inc (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)

1584. In Vitro Activity of Imipenem/Relebactam against Gram-Negative Pathogens from Patients with Bloodstream Infections in the United States and Canada – SMART 2018

BackgroundRelebactam (REL) inhibits class A and C β-lactamases, including KPC, and was approved in the United States combined with imipenem (IMI) and cilastatin for complicated urinary tract and intraabdominal infections. We evaluated the activity of IMI/REL against non-Morganellaceae (NME) and P. aeruginosa collected as part of the global SMART surveillance program from patients with bloodstream infections (BSI) in the US and Canada.MethodsIn 2018, 24 US and 8 Canadian hospitals each collected up to 50 consecutive aerobic or facultative gram-negative pathogens from patients with BSI. MICs were determined using CLSI broth microdilution and interpreted with 2020 CLSI breakpoints. Multidrug-resistance (MDR) was defined as resistance to ≥3 of the following sentinel drugs: amikacin, aztreonam, cefepime, ceftazidime (NME only), ciprofloxacin, colistin, imipenem, and piperacillin/tazobactam.ResultsThe 5 most common species among 1463 collected BSI isolates were E. coli (46.9%), K. pneumoniae (16.0%), P. aeruginosa (8.5%), P. mirabilis (4.8%), and E. cloacae (4.3%). Susceptibility to IMI/REL and comparators of selected species and subsets of resistant phenotypes is shown in the table.IMI/REL was active against 99.8% of NME isolates; only meropenem, ceftazidime/avibactam, and amikacin showed comparable activity. Per 2020 CLSI guidelines, Enterobacterales and P. aeruginosa isolates are no longer considered susceptible to colistin. IMI/REL maintained activity against 89-100% of NME isolates that were nonsusceptible (NS) to β-lactams or MDR. Among P. aeruginosa, IMI/REL was active against 94.4% of isolates; a susceptibility rate only exceeded by amikacin. The addition of relebactam lowered the MIC90 for P. aeruginosa from 16 µg/mL to 1 µg/mL. IMI/REL maintained activity against 40-77% of P. aeruginosa isolates NS to β-lactams or MDR; susceptibility rates only exceeded by amikacin.Susceptibility to IMI/REL was similar in the US (99.8% of NME [n=846]; 93.8% of P. aeruginosa [n=96]) and Canada (99.7% of NME [n=339]; 96.4% of P. aeruginosa [n=28]).Table ConclusionIn the US and Canada, IMI/REL could provide an important treatment option for patients with BSI caused by resistant gram-negative organisms.DisclosuresSibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co, Inc (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)

1588. Activity of Imipenem/Relebactam Against Clinical Isolates of P. aeruginosa and K. pneumoniae Collected in Asia/Pacific Countries – SMART 2016-2018

BackgroundRelebactam (REL) inhibits class A and C β-lactamases and was approved in the USA in combination with imipenem (IMI) and cilastatin for the treatment of complicated intraabdominal and urinary tract infections. We evaluated the activity of IMI/REL against clinical isolates collected in Asia/Pacific as part of the global SMART surveillance program.MethodsIn 2016-2018, 56 clinical laboratories each collected up to 250 consecutive, aerobic and facultative gram-negative pathogens from various infection sources per year. Susceptibility was determined using CLSI broth microdilution and CLSI breakpoints. IMI-nonsusceptible isolates (except from India) were screened for β-lactamase genes.ResultsAmong 5501 K. pneumoniae and 4362 P. aeruginosa isolates, 46.6% and 65.3%, respectively, were collected from patients with lower respiratory tract infections, 25.6% and 17.1% from intraabdominal infections, 19.9% and 13.9% from urinary tract infections, and 7.2 and 2.9% from bloodstream infections. No infection source was specified for 0.7% of isolates from either species. 90.7% of collected K. pneumoniae isolates were IMI/REL-susceptible, ranging from 56.8% in India and ~80% in Thailand and Vietnam (~16% MBL-positive) to ≥97% in 7 countries (0-2% MBL-positive). 28.6% (202/707) of IMI-nonsusceptible K. pneumoniae were IMI/REL-susceptible. Of the 425 molecularly characterized IMI-nonsusceptible K. pneumoniae, 187 (44.0%) were MBL/OXA-48-like negative and 83.4% of these (156/187) were IMI/REL-susceptible; 82 isolates (19.3%) were KPC-positive and 91.5% of these (75/82) were IMI/REL-susceptible.The table shows percent susceptible and percent MBL-positive among all collected P. aeruginosa isolates. 74.3% of IMI-nonsusceptible P. aeruginosa (n=1236) were IMI/REL-susceptible.Table ConclusionIMI/REL was active against 91% of K. pneumoniae and 89% of P. aeruginosa isolates collected in Asia/Pacific overall, with higher activity in countries with lower MBL-positive rates. IMI/REL promises to be an important treatment option for IMI-nonsusceptible MBL-negative isolates, including KPC-producing K. pneumoniae.DisclosuresSibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Krystyna Kazmierczak, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Wei-Ting Chen, MD, Merck, Sharp & Dohme, Taiwan (Employee) Tsz Kin Khan, PhD, Merck, Sharp & Dohme, Hong Kong (Employee) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co, Inc (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)

1619. Meta-analysis of Randomized Control Trials Evaluating New Beta-Lactamase Combination Antibiotics

BackgroundCeftolozane/ Tazobactam (C/T), Ceftazidime/ Avibactam (C/A), Meropenem/ Vaborbactam (M/V) and Imipenem/ Relebactam (I/R) are new combination beta-lactam/ beta-lactamase inhibitor antibiotics primarily used to treat multidrug-resistant (MDR) Gram-negative infections. This study synthesized outcomes of comparative observational studies and randomized control trials (RCTs) that evaluated clinical success of these antibiotics compared to other therapies.MethodsPubMed, EMBASE, and Google Scholar were searched from January 1st, 2013 through October 1st, 2019 for comparative observational studies and RCTs of C/T, C/A, M/V and I/R in patients with pneumonia, complicated intra-abdominal and urinary tract infections. Study and patient demographics were collected along with clinical and microbiological success rates. Meta-regression analysis was used to determine the pooled effectiveness of C/T, C/A, M/V, and I/R. Heterogeneity and publication bias were assessed via I2 values and funnel plots, respectively.ResultsLiterature search returned 1,645 results. After exclusion criteria, 21 publications representing 6,246 patients were retained: 16 RCTs (8 C/A, 3 C/T, 3 I/R, 2 M/V) and 5 comparative observational studies (3 C/A, 2 C/T). Pooled risk ratios for clinical success showed that all four antibiotics were non-inferior to comparator antibiotics (0.99 (95% CI (0.97-1.01)). Eleven of the sixteen RCTs evaluated microbiological success; pooled risk ratio was 1.08 (95% CI 1.04-1.13), indicating that older therapies were more successful at microbiological eradication than newer antibiotics. Only 6 of the included studies (3 RCTs and 2 observational studies) focused on patients with MDR infections. Limiting the analysis to MDR RCTs did not change the overall conclusions.ConclusionAlthough older therapies had slightly higher microbiologic clearance, pooled clinical success rates for C/A, C/T, M/V, and I/R were non-inferior to older therapies, including in studies focused on patients with MDR infections. Additional studies are needed to further evaluate these drugs’ effectiveness for treatment of MDR infections.Disclosures All Authors: No reported disclosures

1609. Epidemiology and Susceptibility to Imipenem/Relebactam of Gram-Negative Pathogens from Patients with Lower Respiratory Tract Infections – SMART United States 2017-2018

BackgroundRelebactam (REL) inhibits class A and C β-lactamases and was approved in the US combined with imipenem (IMI) and cilastatin for complicated urinary tract and intraabdominal infections. Using isolates collected as part of the global SMART surveillance program in the US, we evaluated the activity of IMI/REL against gram-negative pathogens (GNP) from patients with lower respiratory tract infections (LRTI), including a comparison of isolates from ICU and non-ICU wards.MethodsIn 2017-2018, 27 US hospitals each collected up to 100 consecutive aerobic or facultative GNP from LRTI patients per year. MICs were determined using CLSI broth microdilution and breakpoints.ResultsAmong 3878 GNP isolates from LRTI, the most common species collected were P. aeruginosa (Psa, 33.3%), K. pneumoniae (10.9%), E. coli (10.4%), and S. marcescens (6.9%). Susceptibility of GNP is shown in the table.IMI/REL inhibited 93% of Psa and Enterobacterales, which included 174 isolates of Morganellaceae that are not expected to be susceptible to IMI or IMI/REL. S. marcescens also showed low susceptibility to IMI, with improved but still reduced activity upon addition of REL. IMI/REL inhibited 83% of all GNP combined, 7-18 percentage points higher than the comparator β-lactams. Of the tested comparators, only amikacin exceeded the activity of IMI/REL.Only Psa showed substantial differences in susceptibility between isolates from ICU (n=486) and non-ICU wards (n=611), with 63.4% and 70.2%, respectively, susceptible to IMI, 71.6/78.7% to cefepime, and 64.2/73.3% to piperacillin/tazobactam (P/T). Susceptibility to IMI/REL was high in both settings (91.4/93.6%). Among Enterobacterales, susceptibility was generally similar in ICU and non-ICU wards (IMI/REL, 92.5% in both settings; IMI, 86.3 and 87.1%, respectively; cefepime, 89.9/89.0%; P/T, 88.7/87.4%).Table ConclusionAlthough resistance rates have frequently been reported to be higher in ICU than non-ICU wards, this pattern was seen in the current study only among Psa isolates. IMI/REL showed activity >90% against both Enterobacterales and Psa from both ward types. These in vitro data suggest that IMI/REL could provide an important treatment option for patients with LRTI in the US, including those in ICUs.DisclosuresSibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co, Inc (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)

1583. In Vitro Activity of Imipenem/Relebactam against Klebsiella pneumoniae and Pseudomonas aeruginosa from Patients in ICUs in the Asia/Pacific region – SMART 2015-2018

BackgroundRelebactam (REL) is an inhibitor of class A and C β-lactamases approved in the USA in combination with imipenem (IMI) and cilastatin for the treatment of complicated intraabdominal and urinary tract infections. Elevated antimicrobial resistance rates have been reported in ICUs. Using isolates collected in Asia/Pacific for the SMART surveillance program, we evaluated the activity of IMI/REL and comparators against K. pneumoniae (KP) and P. aeruginosa (PA) from ICU patients.MethodsIn 2015-2018, 51 clinical laboratories in Australia, Hong Kong, Malaysia, New Zealand, Philippines, Singapore, South Korea, Taiwan, Thailand, and Vietnam each collected up to 250 consecutive aerobic gram-negative pathogens per year. Susceptibility was determined using CLSI broth microdilution and CLSI and FDA (IMI/REL) breakpoints. IMI-nonsusceptible KP and PA were screened for β-lactamase genes.ResultsAnalyzing only the 6322 isolates from ICU patients, the 3 most common species collected were KP (21.4%), E. coli (20.5%), and PA (19.7%). Tables 1 and 2 show % susceptible and % MBL- and/or OXA-48-like-positive for the most common Enterobacterales species (KP; 70.6% from lower respiratory tract, 17.6% from intraabdominal, 7.1% from urinary tract, and 4.1% from bloodstream infections) and the most common non-Enterobacterales species (PA; 83.6%, 9.9%, 4.3%, and 1.9%, respectively). % IMI/REL-susceptible ranged from 66-79% in Thailand and Vietnam (where 13-36% of isolates carried MBL and/or OXA-48-like carbapenemases, which REL does not inhibit) to ≥95% in 6 countries (0-3% MBL- and/or OXA-48-like-positive). Among 103 IMI/REL-nonsusceptible KP isolates, 66.0% carried MBL, 20.4% OXA-48-like carbapenemases, 2.9% KPC, 2.9% acquired AmpC and/or ESBL, and in 7.8% no acquired β-lactamases were detected. Among 145 IMI/REL- nonsusceptible PA, 54.5% carried MBL, 1.4% GES carbapenemases, 4.1% only ESBL, and 40.0% no acquired β-lactamases.Table 1. Antimicrobial susceptibility of K. pneumoniae collected from ICU patients Table 2. Antimicrobial susceptibility of P. aeruginosa collected from ICU patients ConclusionIMI/REL was active against 92% of KP and 88% of PA from ICU patients in Asia/Pacific overall, with higher activity in countries with lower prevalence of MBL or OXA-48-like carbapenemases. IMI/REL provides a potential treatment option for ICU patients in Asia/Pacific with infections caused by KP and PA.DisclosuresSibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Consultant) Wei-Ting Chen, MD, Merck, Sharp & Dohme, Taiwan (Employee) Yivonne Khoo, PhD, Merck, Sharp & Dohme, Malaysia (Employee) Kanchan Balwani, MBBS, MS, Merck, Sharp & Dohme, Hong Kong (Employee) Katherine Young, MS, Merck & Co., Inc. (Employee, Shareholder)Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co, Inc (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)

1608. Efficacy of Ceftolozane/Tazobactam for Multidrug-Resistant Gram-Negative Infections in Multiple Urban Hospitals

BackgroundCeftolozane/tazobactam (C/T) is a novel cephalosporin/beta-lactamase inhibitor combination developed for use against multidrug-resistant (MDR) Gram-negative infections, particularly Pseudomonas aeruginosa (PA). C/T is approved for complicated urinary tract and intraabdominal infections as well as hospital-acquired/ventilator-associated bacterial pneumonias. However, comprehensive clinical characterization of patients treated with C/T in non-FDA-approved indications is limited.MethodsPatients ≥18 years who received C/T for ≥48 hours while hospitalized in 9 acute care centers in Houston, TX from January 2016 through September 2018 were included. Demographic, microbiologic, treatment and clinical outcome data were retrospectively collected by chart review. In patients who received multiple inpatient courses of C/T, only the first course with C/T was assessed.Results210 patients met inclusion criteria: 58% were non-white, 35% were female and 13% were immunocompromised. Median age was 61 years (IQR, 48 to 69). Median Charlson comorbidity index was 5 (IQR, 2 to 6). At the onset of the index episode, a significant proportion of patients required intensive care unit admission (44%), mechanical ventilation (37%) and pressor support (22%). Respiratory sources were the most common (50%) followed by urine (15%). Positive cultures were documented in 93% of the cases and PA was found in 86%. Majority (95%) of PA which were MDR. C/T use was guided by susceptibility testing of the index isolate in ca. 52%. In 5.7% of cases, C/T was used to escalate therapy without any documented C/T-susceptible organism. Half (51%) of the cohort received initial dosing appropriate for renal function while 36% receiving a lower than recommended dose. Clinical success (i.e., recovery from infection-related signs and symptoms) occured in 77%. The in-hospital mortality rate in our cohort was 15% with 26 of 31 deaths deemed infection-related.ConclusionWe report a large multicenter observational cohort that received C/T. A 77% clinical success with the use of C/T was documented. These data support the use of C/T in critically ill patients infected with MDR PA.DisclosuresWilliam R. Miller, MD, Entasis Therapeutics (Scientific Research Study Investigator)Merck (Grant/Research Support)Shionogi (Advisor or Review Panel member) Laura A. Puzniak, PhD, Merck (Employee) Cesar A. Arias, MD, MSc, PhD, FIDSA, Entasis Therapeutics (Scientific Research Study Investigator)MeMed (Scientific Research Study Investigator)Merck (Grant/Research Support)

1589. Activity of Meropenem-Vaborbactam and Comparators against Globally Disseminated Klebsiella pneumoniae Sequence Type 258

BackgroundMeropenem-vaborbactam (MVB) is a combination of a carbapenem and a b-lactamase inhibitor active against β-lactamases including serine carbapenemases. MVB recently was approved in the US and Europe for the treatment of complicated UTIs, including acute pyelonephritis, and is approved in Europe for treatment of complicated intra-abdominal infections, hospital-acquired bacterial pneumonia, ventilator-associated pneumonia, and bacteremia. Carbapenemase-producing Enterobacterales (ENT) isolates, particularly Klebsiella pneumoniae (KPN), have disseminated worldwide and are considered endemic in various countries. Carbapenem-resistant (CR) KPN outbreaks have been associated with KPN sequence-type 258 (ST258). Globally, 60-70% of KPC-producing KPN belong to ST258. In this study, we examined the susceptibilities of ST258 isolates collected as a part of the SENTRY global surveillance program.MethodsKPN isolates from 2016-2019 were susceptibility tested by reference broth microdilution methods. The results were interpreted using CLSI 2020 breakpoints. The sequence type and presence of carbapenemases were determined by whole genome sequencing and analysis.Results130 KPN ST258 isolates were identified in 6 countries. All isolates were extremely drug resistant (XDR, susceptible to < = 1 agent in 2 or fewer drug classes). 76.2% were CR, and 71 isolates contained blaKPC-2, 25 blaKPC-3 and 1 blaKPC-12. One isolate contained blaNDM-1. The US had the most ST258 isolates (n=56), of which 22 produced KPC-2 and 19 produced KPC-3. Greece had 32 isolates, with 17 KPC-2 and 5 KPC-3. Brazil had 22 isolates, 17 with KPC-2. The single NDM-1 producing isolate was from Argentina. Susceptibilities to MVB and comparators by country are shown in the table. MVB inhibited 99.2% of the isolates and was the most active agent overall, only 23.1% were meropenem susceptible. Tigecycline was the most active comparator with 98.5% susceptible.ConclusionThese results demonstrate MVB has potent activity against the internationally disseminated KPN clone ST258 including those producing KPC. MVB may be useful for the treatment of infections caused by XDR K. pneumoniae.Table 1 Disclosures Timothy B. Doyle, Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Jennifer M. Streit, BS, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support)

1259. Activity of eravacycline against staphylococci isolated from periprosthetic joint infections

BackgroundPerirosthetic joint infections (PJIs) are costly and difficult to treat. The most common causes of PJIs are Staphylococcus aureus and Staphylococcus epidermidis. Eravacycline is a newer tetracycline with promising activity against Gram-positive and negative bacteria which is approved for treatment of complicated intraabdominal infections. Here, the in vitro activity of eravacycline was assessed against bacteria associated with PJI.Methods185 staphylococcal isolates, including 38 methicillin-resistant S. aureus (MRSA), 64 methicillin-susceptible S. aureus (MSSA), 62 methicillin-resistant S. epidermidis (MRSE) and 21 methicillin-susceptible S. epidermidis (MSSE) strains were studied. Minimum inhibitory concentrations (MICs) were determined according to Clinical and Laboratory Standards Institute guidelines (range of 0.06-64 µg/ml tested). Results were analyzed using susceptible breakpoints from EUCAST (≤0.25 µg/ml) and the FDA (≤0.06 µg/ml). Minimum biofilm bactericidal concentrations (MBBCs) were determined using a modification of the Calgary biofilm method. Briefly, biofilms were formed on pegged lids in trypticase soy broth, after which the pegged lids were rinsed in phosphate buffered saline (PBS), transferred to a plate containing dilutions of eravacycline in cation-adjusted Mueller Hinton broth (CAMHB) and incubated for 20-24h. Finally, the pegged lids were again rinsed in PBS and transferred to a plate containing CAMHB and incubated for 24h. The MBBC was the lowest concentration with no visible growth.ResultsMIC50/90 (range) in µg/ml for MRSA, MSSA, MRSE, and MSSE were 0.125/0.125 (≤0.06-0.25), ≤0.06/0.125 (≤0.06-0.25). 0.125/1 (≤0.06-2), and 0.25/1 (≤0.06-1), respectively. Using the EUCAST susceptible breakpoint, 100% of isolates would be considered susceptible, whereas only 54% would be considered susceptible using the FDA breakpoint. MBBC50/90 (range) in µg/ml for MRSA and MSSA were both 8/16 (4-16); for MRSE and MSSE, the values were 4/16 (2-32) and 8/16 (2-32), respectively.ConclusionOur data suggest that the FDA susceptible breakpoint may need re-evaluation. Eravacycline has low anti-staphylococcal biofilm activity.DisclosuresRobin Patel, MD, Accelerate Diagnostics (Grant/Research Support)CD Diagnostics (Grant/Research Support)Contrafect (Grant/Research Support)Curetis (Consultant)GenMark Diagnostics (Consultant)Heraeus Medical (Consultant)Hutchison Biofilm Medical Solutions (Grant/Research Support)Merck (Grant/Research Support)Next Gen Diagnostics (Consultant)PathoQuest (Consultant)Qvella (Consultant)Samsung (Other Financial or Material Support, Dr. Patel has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued.)Selux Dx (Consultant)Shionogi (Grant/Research Support)Specific Technologies (Consultant)

915. Global 2018 Surveillance of Eravacycline Against Gram-positive Pathogens, Including Resistant Isolates

BackgroundEravacycline (ERV) 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 purpose of this study was to further monitor the in vitro activity of ERV against Gram-positive pathogens, such as Staphylococcus aureus (including methicillin-resistant S. aureus, MRSA), Enterococcus spp. (including vancomycin-resistant Enterococcus, VRE) and Streptococcus spp.MethodsIsolates were collected globally during 2018 from various body sites. Minimum inhibitory concentrations (MICs) were determined by CLSI broth microdilution. Antibiotic susceptibility was determined using the most recent CLSI breakpoints (30th ed CLSI M100 document), except for ERV and tigecycline (TGC) where FDA breakpoints from 2018 and 2005, respectively, were applied.ResultsSummary MIC data for ERV and select comparators are shown in the Table. ERV MIC50/90 for Enterococcus spp were 0.06/0.12 μg/mL and were not affected by the presence of vancomycin resistant mechanisms. The MIC90 of ERV against VRE was 2-fold lower than TGC, at a value of 0.12 μg/mL. ERV MIC90 values for methicillin-susceptible S. aureus (MSSA) was 0.12 μg/mL and for MRSA was 0.25 μg/mL. Generally, for all pathogens, ERV MIC90 values were 2- to 4-fold lower than TGC.Table ConclusionERV in vitro activity was demonstrated for clinically important Gram-positive pathogens, including resistant isolates. Overall, ERV demonstrated lower MIC90 values than comparators for all organisms. This 2018 global surveillance highlights ERV’s utility against Gram-positive organisms and further underscores its role in cIAI, where these pathogens play a causative role.DisclosuresSteven Morgan, PharMD, Tetraphase Pharmaceuticals (Employee) Sara Hwang, PharMD, Tetraphase Pharmaceuticals (Employee) Ekaterina Efimova, PharMD, Tetraphase Pharmaceuticals (Employee) Stephen Hawser, PhD, Tetraphase Pharmaceuticals (Scientific Research Study Investigator) Virgil Lijfrock, PharMD, Tetraphase (Employee)

1577. Real-World, Multicenter Experience with Eravacycline for Various Infections

BackgroundEravacycline (ERV) is Food and Drug Administration approved in patients for the treatment of adults complicated intra-abdominal infections in 2018. Real-world data regarding the indications for ERV use are is limited. We evaluated the clinical/safety outcomes of patients treated with ERV in FDA and non-FDA approved indications.MethodsMulticenter, retrospective, observational study from September 2018 to June 2020. Adult patients treated with ERV for ³ 72 hours were included. The primary outcome was 30-day survival. Secondary outcomes included a lack of 30-day infection-recurrence, resolution of signs/symptoms of infection and safety. All outcomes were measured from ERV start date.ResultsOverall, 108 patients were included from 12 geographically-distinct medical centers across the United States. The median(IQR) age was 60(52-67) years and 60% were male. Median(IQR) APACHE II and Charlson Comorbidity scores were 15(11-21) and 3 (2-6), respectively. The most common sources of infection were intra-abdominal (32%), and respiratory (24%). Common pathogens included Acinetobacter baumannii (19%), Klebsiella pneumoniae and Enterococcus faecium (16%). Infectious diseases consultation was obtained in 98%, and surgical interventions in 51% of cases. Patients often received active therapy prior to ERV(40%). Median(IQR) ERV therapy duration was 7.7(4.4-14.0) days. Among cases with documented cultures, ERV was initiated within a median(IQR) of 4.8(2.5-9.9) days. Combination therapy ³ 48 hours was given in 45%. The primary endpoint was achieved in 79%(85/108). Of patients who died(n=23), 57% were on monotherapy, 39% were critically ill, 39% had intra-abdominal as a source, and 30% had positive blood cultures. For secondary outcomes, 94%(102/108) lacked 30-day infection-recurrence and 74%(80/108) resolved signs/symptoms of infection. ERV was selected primarily for consolidation of the regimen(40%). Eight patients experienced a probable ERV-related adverse event, mainly gastrointestinal(87.5%) and none experienced clostridium difficile.Conclusion30-day survival was achieved in the majority of patients treated with ERV. Studies with longer follow-up are required to confirm these findings.DisclosuresMadeline King, PharmD, Tetraphase (Speaker’s Bureau) Bruce M. Jones, PharmD, BCPS, ALK-Abello (Research Grant or Support)Allergan/Abbvie (Speaker’s Bureau) Michael J. Rybak, PharmD, MPH, PhD, Paratek (Grant/Research Support)

1613. Global 2018 Surveillance of Eravacycline Against Gram-negative Pathogens, Including Multi-drug Resistant Isolates

BackgroundEravacycline (ERV) is a fully-synthetic, fluorocycline antibacterial approved by the FDA and EMA for treatment of complicated intra-abdominal infections (cIAI) in patients ≥18 years of age. The purpose of this study was to describe the in vitro activity of ERV against Gram-negative pathogens, including multi-drug resistant (MDR) isolates, collected in 2018.MethodsIsolates were collected during 2018 from various body sites. Minimum inhibitory concentrations (MICs) were determined by CLSI broth microdilution. Antibiotic susceptibility was determined using the most updated CLSI breakpoints, except for ERV and tigecycline (TGC) where FDA breakpoints established in 2018 and 2005 respectively, were used. MDR was defined as resistance to ≥3 antibiotics from aztreonam, a carbapenem (meropenem or ertapenem [ETP]), cefepime/cefotaxime/ceftazidime/ceftriaxone (any one), gentamicin, levofloxacin, piperacillin-tazobactam TZP, tetracycline or TGC.ResultsSummary MIC data for ERV and select comparators are shown in the Table. ERV MIC90 for all-Enterobacteriaceae was 0.5 μg/ml and for MDR-Enterobacteriaceae was 1μg/ml. The susceptibilities for all-Enterobacteriaceae were 93%, 95%, 93% and 82% for ERV, TGC, ETP and TZP, respectively. ERV further demonstrated higher rates of susceptibility than ETP and TZP against MDR-Enterobateriaceae, 81% vs 71% vs 38%. ERV MIC50/90 for carbapenem-resistant Acinetobacter baumannii (CRAB) were 4-fold lower than TGC.Table ConclusionERV in vitro activity was demonstrated and comparable susceptibility rates were observed for clinically important Gram-negative pathogens, including resistant isolates. Overall, ERV MIC90 values were 2- to 8- fold lower than TGC. this study further highlights the in vitro activity of ERV against Gram-negative pathogens identified in patients with cIAI.DisclosuresVirgil Lijfrock, PharMD, Tetraphase (Employee) Steven Morgan, PharMD, Tetraphase Pharmaceuticals (Employee) Sara Hwang, PharMD, Tetraphase Pharmaceuticals (Employee) Ekaterina Efimova, PharMD, Tetraphase Pharmaceuticals (Employee) Kenneth Lawrence, PharmD, Tetraphase Pharmaceuticals (Employee) Stephen Hawser, PhD, Tetraphase Pharmaceuticals (Scientific Research Study Investigator) Ian Morrissey, PhD, Tetraphase Pharmaceuticals (Scientific Research Study Investigator)

1270. Early Real-world Evidence in the Use of Eravacycline for the Management of Draconian Infections

BackgroundEravacycline (ERV) is a next-generation tetracycline approved for complicated intra-abdominal infections (cIAI) with in-vitro activity to multidrug-resistant organisms such as carbapenem resistant Enterobacteriaceae, extended spectrum beta-lactamase, and carbapenem-resistant Acinetobacter baumannii (CRAB). The purpose of this study was to identify the utility of ERV in clinical practice.MethodsRetrospective case series was conducted on patients at AdventHealth that received at least two doses of ERV. Primary endpoint for the study was clinical success while on ERV, meeting none of the following criteria: changing therapy, mortality, or lack of improvement from sign/symptoms.ResultsOf 23 patients, 74% were males with a mean age of 55 ±18 years and mean body weight of 79 ±27 kg. Mean APACHE II and Charleson scores were 20 (±11) and 6 (±4), respectively. 91% received ERV for an off-label indication or organism. Infection types were respiratory (44%), cIAI (35%), skin (9%), and other (13%). All patients had positive cultures, while 61% were treated as a polymicrobial infection and 17% had bacteremia. Microorganisms included A. xylosoxidans, S. maltophilia, CRAB, and K pneumoniae. 48% had ERV susceptibilities from .06-4 mcg/mL, including two MIC ≥32mcg/mL for S. maltophilia. 70% were given another antibiotic prior to ERV with a median duration of 5 (1-35) days. Median duration of ERV was 8 (3-30) days. 83% percent received ERV in combination with another antibiotic. During treatment, 26% had a Child-Pugh Class C at baseline and 30% had elevated liver function tests. No adverse drug reactions were reported. Upon discharge, 35% continued ERV. Clinical success was observed in 57% (12/21) of patients. Clinical outcome by infection type is summarized in Figure 1. Of 9 cases of clinical failure, 14% were changed to alternative, 19% died while on ERV, and 10% failed to resolve signs/symptoms. Two cases of M. abscessus infections had insufficient follow-up to assess clinical outcome.Figure 1. Eravacycline Clinical Outcome by Infection Type ConclusionInitial real-world experience with ERV differs significantly from the trials regarding severity of illness, types of infection, and clinical outcomes. Further evaluation is necessary for using ERV as combination therapy and in off-label indications.Disclosures All Authors: No reported disclosures

Susceptibility trends of ceftolozane/tazobactam and comparators when tested against U.S. gram-negative bacterial surveillance isolates (2012–2018)

Ceftolozane/tazobactam is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor. Ceftolozane/tazobactam has been approved in >60 countries for treating complicated urinary tract infections, acute pyelonephritis, complicated intra-abdominal infections (with metronidazole), and hospital-acquired pneumonia, including ventilator-associated pneumonia in adults. We analyzed susceptibilities for 35,882 gram-negative isolates collected from patients in 35 US medical centers from 2012 to 2018. The rate of multi-drug resistant Enterobacterales was stable (9.5%–10.1%), while the P. aeruginosa multi-drug resistance rate increased from 15.5% in 2012 to 22.9% in 2018. The carbapenem-resistant Enterobacterales rates varied from 0.9% to 2.2% and extended-spectrum β-lactamase phenotypes increased from 10.5% to 16.8%. The most active drugs against P. aeruginosa were ceftolozane/tazobactam (95.8%–97.5% susceptible) and amikacin (93.9%–98.0%); against Enterobacterales, amikacin (97.9%–98.8%), meropenem (97.7%–98.8%), and ceftolozane/tazobactam (93.3%–95.6%) were the most active. These data suggest that ceftolozane/tazobactam has effective in vitro activity against organisms causing serious gram-negative infections.

The Potential Prognostic Performance of Neutrophil CD64 and Monocyte HLA-DR in Patients with Complicated Intra-abdominal Infections

Background: Complicated intra-abdominal infections are still associated with a high risk of an unfavorable outcome. Despite the equal treatment, the mortality rates in some patients’ populations remain significant, especially when the impaired immune response is present. Aim: The object of this research is to analyze the impact of pro-inflammatory neutrophil CD64 and anti-inflammatory monocyte HLA-DR on the final outcome. Methods: We have searched in the PubMed database, the literature relating the prognostic value of two biomarkers - nCD64 and mHLA-DR in patients with complicated intra-abdominal infections and/or sepsis. Results: Eighteen original studies with 2960 patients fulfilled our inclusion criteria. The data about nCD64 that we found was contradictory, whereas low mHLA-DR expression showed good prognostic value. Conclusion : Our review showed heterogeneous data about nCD64 survival prediction. Further investigations with surgical patients exclusively are needed to evaluate its prognostic value in cIAIs. However, we observed a good prognostic performance of low mHLA-DR expression. After a validation in larger multicentre studies, mHLA-DR could be used as promising prognostic biomarker in cIAIs.

Abdominal sepsis

Background. Sepsis is a life-threatening acute organ dysfunction that occurs as a result of dysregulation of the macroorganism’s response to infection. Septic shock is a variant of sepsis characterized by the circulatory failure, manifested by hypotension and increased lactate levels &gt;2 mmol/L despite adequate infusion, which requires the administration of vasopressors to maintain average blood pressure &gt;65 mm Hg.&#x0D; Objective. To describe the management of patients with abdominal sepsis.&#x0D; Materials and methods. Analysis of literature data on this topic.&#x0D; Results and discussion. Complicated intra-abdominal infection (IAI) is the growth of pathogenic microorganisms in a usually sterile abdominal cavity, usually due to the perforation of the hollow organs. Uncomplicated IAI involves transmural inflammation of the digestive tract, which does not spread beyond the hollow organ. If uncomplicated IAI are not treated, there is a possibility that they will progress to complicated ones. Measures to control the source of infection include the drainage of abscesses or places of accumulation of infected fluid, removal of necrotic infected tissues and restoration of the anatomy and functions of the affected area. Several multivariate studies have found that failure to adequately control the source of infection is a risk factor for adverse outcomes and death in patients with IAI. Surviving sepsis and other recommendations also support the need for early control of the source of infection. In a study by B. Tellor et al. (2012) mortality was 9.5 % among individuals with adequate control of the infection source and 33.3 % among patients who failed to achieve such control. In some situations, it is advisable to manage patients conservatively. Thus, in appendicular infiltration, most studies have demonstrated the benefits of conservative management (Andersson R.E., Petzold M.G., 2007). Management of IAI without final control of the primary source is possible in cases where the organism has already overcome the infection, and surgery can only increase the number of complications. In general, patients with localized infections may need less invasive management. Thus, percutaneous drainage can be used for localized accumulations of fluid in the abdominal cavity. 80-92 % of drainage procedures are successful on the first attempt. &lt;5 % of patients require surgical treatment. Such drainage procedures are used in infected pancreatic necrosis, and the final debridement of the infection source may be delayed. In critically ill patients, damage control laparotomy and limited intervention (resection without reanastomosis or stoma formation, temporary drainage and tamponade of the abdominal cavity if necessary, temporary closure of the abdominal cavity) are performed to control the infection. Indications for damage control laparotomy include inability to achieve adequate control of the source of IAI during primary laparotomy, hemodynamic instability, the need to re-evaluate the condition of the problematic anastomosis, and diffuse peritonitis. A prospective study of staged laparotomies revealed a shorter length of stay in the intensive care unit, a lower incidence of complications and lower treatment costs using this method compared to the standard one. Antibacterial support of surgical interventions is an important aspect of treatment. In conditions of increasing antibiotic resistance, antibiotics should be prescribed strictly in accordance with the recommendations and for as short effective period as possible.&#x0D; Conclusions. 1. Despite the fact that approaches are changing, control of the IAI source remains the main method of treatment of most patients with IAI. 2. The choice of empirical antibacterial therapy should be based on the risk assessment and potential of resistant bacteria. 3. The duration of antimicrobial therapy can be significantly reduced (4 days).