BackgroundCeftriaxone–Sulbactam–EDTA (CSE) is the first cephalosporin–β-lactamase inhibitor combination with an antibiotic resistance breaker–disodium edetate, recently evaluated in a Phase 3 clinical trial for treatment of adults with complicated urinary tract infections (NCT03477422). The addition of Sulbactam and EDTA expands the spectrum of activity of Ceftriaxone to include extended-spectrum-β-lactamase (ESBL) and metallo-β-lactamase (MBL) producing bacteria. This study evaluated the in vitro activity of CSE against 3,150 isolates (716 (22.73%) E. coli; 435 (13.81%) K. pneumoniae; 1,075 (34.13%) A. baumannii; 924 (29.33%) P. aeruginosa) collected from 22 hospitals in India during 2013–2016.MethodsA total of 3,150 nonduplicate Gram-negative clinical isolates were collected, and susceptibility testing was conducted using reference broth microdilution method for CSE and comparators. CLSI defined phenotypic methods were used for ESBL and MBL detection, and thereafter, all isolates were further characterized genotypically using single PCRs and a panel of primers for detection of most β-lactamase enzymes, including blaTEM, blaSHV, blaCTX-M, blaAmpC, blaOXA, blaKPC, blaVIM, blaNDM, and blaIMP.ResultsOf the 3,150 isolates, 2,717 (86.25%) were β-lactamase producers, of which, 851 (31.32%) tested positive for ESBL, 1,591 (58.56%) tested positive for MBL, while 275 (10.12%) tested positive for both ESBL and MBL production during phenotypic evaluation. Once the genotype data were available, isolates were re-characterized as per the functional classification of β-lactamases into four distinct categories, including ESBL, AmpC, Carbapenemase and MBL. An astonishing 1,866 (59.23%) isolates harbored at least one MBL gene, of which, the prevalence was the highest in A. baumannii (78.6%), followed by K. pneumoniae (63%), P. aeruginosa (46.6%) and E. coli (44.1%). A summary of the results of susceptibility testing is shown in Figures 1, 2, and 3. ConclusionCSE showed a high overall susceptibility in ESBL- and MBL-producing bacteria and could provide a useful alternative to carbapenems and colistin in clinical settings.Disclosures R. Girotra, Venus Medicine Research Centre: Employee, Salary. A. Pyasi, Venus Medicine Research Centre: Employee, Salary. M. Chaudhary, Venus Medicine Research Centre: Board Member and Shareholder, Salary. M. A. Mir, Venus Medicine Research Centre: Employee, Salary. S. Chaudhary, Venus Medicine Research Centre: Employee and Shareholder, Salary. P. Mandale, Venus Medicine Research Centre: Employee, Salary.

Introduction: In the light of changing anti-microbial resistance pattern, the understanding of the local antibiogram is essential in the antibiotic selection procedures and preparation of hospital antibiotic policy. Aim: This retrospective study was aimed to analyze the antibacterial susceptibility pattern of major isolates from ICU and IPD. Materials and Methods: Antimicrobial susceptibility testing was done for a total of 565 Gram-negative isolates including E. coli, K. pnuemoniae, A. baumannnii and P. aeruginosa from ICU and IPD patients enrolled between July 2016 to December 2016. Results: The majority of the isolates were reported from urine samples (52%) in IPD and sputum (59%) in ICU. The susceptibility to BL/BLI was 50-75% in IPD patients and Carbapenem susceptibility was reported in more than 75% except P. aeruginosa. In ICU patients, the beta-lactam/beta-lactam inhibitor (BL/BLI) susceptibility ranged between 20-60% and the carbapenem susceptibility was around 40%-75%. The susceptibility of CSE-1034 (Ceftriaxone + Sulbactam + EDTA) was almost similar to minocycline and amikacin ranging from 50-90% against different species. Compared to carbapenems, the CSE-1034 performed overall better than carbapenems against P. aeruginosa and A. baumannii and was comparable to carbapenems against Enterobacteriaceae. The susceptibility of colistin ranged from 92-97% in both IPD and ICU isolates. Conclusion: Considering the value of carbapenems and colistin as the last option for multi-drug resistant (MDR) bacterial infections, irrational prescription of these drugs should be stopped. The use of ampicillin-sulbactam, cefepime and gentamicin from 1st line antibiotics in ICU patients can help to reduce the load on 2nd line antibiotics. Among 2nd line drugs, CSE-1034 along with amikacin should be an empirical choice of treatment for bacterial infections where the 1st line drugs are suspected to fail and the need of carbapenems arises.

Background: The choice of choosing right anti-microbial therapy in hospitals depends on the knowledge of local anti-microbial susceptibility profile. This retrospective study was conducted to assess the in vitro susceptibility pattern of different pathogen isolates to various antibiotics including Cefepime-Amikacin-Antibiotic resistant breakers (ARBs)* in various hospitals across the Jaipur City. Methods: To characterize the antimicrobial susceptibility pattern of different isolates from various hospitals across the Jaipur City, a retrospective, observational analysis was done for antibiogram data. A total of 1201 Gram negative isolates collected during the period from January 2017 to December 2017 were included in the study. Antibiotic sensitivity testing was done in accordance with the recommendations of Clinical Laboratory Standard Institute (CLSI) guidelines. Results: Of the total 1201 Gram negative isolates included in this study, 51.6% were from wounds and pus specimens, 40.1% were from respiratory and 8.2% from blood. P. aeruginosa (49.7%) was the most frequently isolated pathogen distantly followed by A. baumannii (21.6%), K. pneumoniae (16.6%) and E. coli (12.1%). The highest susceptibility was reported to polymyxins (100%) including Colistin and Polymyxin B, among all the tested bacteria’s and system wise. Among all the antibiotic tested, (Cefepime-Amikacin-ARBs*) sensitivity ranged for 87.9% to 52% on pathogens (E. coli, K. pneumonia, P. aeruginosa) tested from samples of skin and soft tissue, respiratory tract, blood stream, followed by Meropenem ranged for 78.4% to 55% on pathogens (E. coli, K. pneumonia, P. aeruginosa), followed by ceftazidime-tazobactam ranged for 82.7% to 58% on pathogens (E. coli, K. pneumonia, P. aeruginosa) and 22.7% sensitive for A. baumannii to Cefoperazone sulbactam. Based on pathogen type, E. coli exhibited highest overall susceptibility and the lowest was reported by A. baumannii. The susceptibility of A. baumannii ranged from 1-26% to all the tested antibiotics except polymyxins with 100% susceptibility. Conclusions: This in vitro susceptibility data suggests that Cefepime-Amikacin-ARBs* can serve as important therapeutic option for the treatment of various resistant Gram-negative bacterial infections to relieve the excess pressure on last resort antibiotics, carbapenems and other drugs including Colistin and polymyxin B. Cefepime-Amikacin-ARBs*on the basis of antimicrobial susceptibility data can be considered as an effective therapeutic option for carbapenems in treating gram negative bacterial infections, and could be considered as a broad spectrum antibiotic sparer’s like carbapenem, colistin and Polymyxin B.

BackgroundCeftriaxone–sulbactam–disodium EDTA (CSE) is being developed for Gram-negative infections caused by multidrug-resistant (MDR) bacteria. PLEA was a Phase 3, double-blind, multicenter, randomized study of CSE vs. meropenem (MR) for treatment of adults with complicated urinary tract infections (cUTI) or acute pyelonephritis (AP). Non-inferiority of CSE over MR at the EMA/FDA primary endpoints has been reported. The effect of baseline MIC on clinical and microbiological outcome at the test of cure (TOC) visit was investigated.MethodsAdult patients were randomized 1:1 to receive either CSE (1 g ceftriaxone/500 mg Sulbactam/37 mg EDTA) every 12 h or MR 1g every 8 hours as 30 minutes IV infusion for 5–14 days. Oral step-down therapy was not allowed. Prior to dosing, urine specimens were collected, and MICs were conducted using CLSI methods for both study drugs. Patients that were nonsusceptible to MR were not included in the mMITT population.ResultsOf 230 subjects randomized, 143 (62.2%) were included in the mMITT population. Baseline Enterobacteriaceae was found in 131 (91.6%) patients, 67/74 (90.5%) in CSE and 64/69 (92.8%) in MR arm. Mean duration of IV therapy was 7 days. Favorable clinical and microbiological outcomes were observed in ≥90% patients for all MICs across the two study groups, with the exception of MIC 1 μg/mL in MR (associated with >20% failures). Overall, both clinical cure and microbiological eradication rates were higher in CSE as compared with MR (95.9% Vs. 89.9% and 94.6% vs. 88.4% respectively) (Table 1).CSEMRMIC(μg/mL)Clinical Cure n/N (%)Microbiological Eradication n/N (%)MIC(μg/mL)Clinical Cure n/N (%)Microbiological Eradicationn/N (%)<0.2516/16 (100)16/16 (100)<0.2520/22 (90.9)21/22 (95.4)0.254/4 (100)4/4 (100)0.2512/12 (100)11/12 (91.7)0.53/3 (100)2/3 (66.7)0.514/14 (100)13/14 (92.7)19/10 (90)9/10 (90)116/21 (76.2)16/21 (76.2)223/23 (100)23/23 (100)416/17 (94.1)16/17 (94.1)80/1 (0)0/1 (0)Overall71/74 (95.9)70/74 (94.6)Overall62/69 (89.9)61/69 (88.4)ConclusionCSE showed a high in vitro–in vivo correlation of >97% for MICs up to 4 μg/mL and is a potential new treatment option in patients with cUTI or AP.Disclosures P. Mandale, Venus Medicine Research Centre: Employee, Salary. M. A. Mir, Venus Medicine Research Centre: Employee, Salary. S. Chaudhary, Venus Medicine Research Centre: Employee and Shareholder, Salary. M. Chaudhary, Venus Medicine Research Centre: Board Member and Shareholder, Salary. A. Pyasi, Venus Medicine Research Centre: Employee, Salary.

Background: Although rare, infection is considered to be most dreadful of the prosthetic related complications resulting in repeated surgical intervention, extended hospitalization or sometimes in loss of implant or permanent disability if not treated promptly. Poor treatment outcome associated with prosthetic joint infections (PJIs) could be partly attributed to rise in anti-microbial resistance among the causative agents. Case Presentation: This is a first reported case of ceftriaxone + sulbactam + ethylenediaminetetraacetic acid (CSE 1034) being used as an de-escalation therapy for more than 24 days with good safety and efficacy outcome in a 78 year male patient with PJI associated with hip replacement surgery, treated initially with meropenem and colistin followed by prolonged de-escalation therapy (24 days). Conclusions: In clinically complicated cases of deep infections where prolonged use of last resort antibiotics is used, CSE-1034 can be considered as a safe, efficacious and economical de-escalating antibiotic to complete the treatment course and prevent recurrence of infection, especially in PJI.