scholarly journals 1181. Use of the Combination Antibiogram in the Era of MDR Gram-Negative Pathogens

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S357-S357
Author(s):  
Kenneth Klinker ◽  
Kartikeya Cherabuddi ◽  
Mark Redell ◽  
Matthew Balogh ◽  
Jill Massey ◽  
...  

Abstract Background Combinations of two or more antimicrobial agents are frequently used in empiric therapy regimens to ensure at least one agent demonstrates activity against suspected pathogens. A combination antibiogram can assess the increase in empiric coverage of a particular combination vs. either of the agents alone (i.e., percent gain). These data could assist in developing empiric regimens that may be particularly useful in settings with problematic multidrug-resistant Gram-negative pathogens. Methods An Excel-based model to construct combination antibiograms was developed to assist clinicians in evaluating institutional susceptibility data. The University of Florida Health Shands Hospital microbiology laboratory supplied susceptibility data for ceftriaxone (CFX), cefepime (CEF), ciprofloxacin (CIP), and amikacin (AMI) to assess % gain achieved with combinations for E. coli all blood isolates (n = 206) and blood isolates with an ESBL phenotype (n = 35). The same laboratory provided susceptibility data for CEF, piperacillin–tazobactam (PTZ), AMI and CIP for P. aeruginosa (all, n = 250; carbapenem-resistant (CARB-R), n = 30). Results Percent gains achieved by adding AMI or CIP to CFX and CEF to capture at least one agent exhibiting in vitro susceptibility against all blood E. coli were calculated: CFX-AMI, 16%; CFTX-CIP, 3%; CEF-AMI, 10%; CEF-CIP, 1%. The percentage gain specific to E. coli blood isolates with an ESBL phenotype ranged from 9% to 86%. The combination with the greatest percent loss against blood E. coli isolates, comparing all blood isolates to those with an ESBL phenotype, was CFX-CIP (∆-66%). Percentage gain achieved against all isolates of Pa by adding AMI or CIP to PTZ and CEF were CEF-AMI, 8%; CEF-CIP, 5%; PTZ-AMI, 15%; PTZ-CIP, 9%; percent gain of the same combinations against P. aeruginosa CARB-R isolates were 23%, 10%, 47%, and 30%, respectively. Adding AMI to either β-lactam: PTZ % S increased from 47% to 77% (+CIP) and to 94% (+AMI); CEF % S increased from 60% S to 70% (+CIP) and to 83% (+AMI). Conclusion Combination antibiogram models can assist clinicians in identifying regimens which may provide improved targeting of MDR phenotypes through calculation of percent gain. Disclosures K. Klinker, Melinta Therapeutics: Consultant, Speaker honorarium. Nabriva Therapeutics: Scientific Advisor, Consulting fee. M. Redell, Melinta Therapeutics, Inc.: Employee and Shareholder, Salary. M. Balogh, Melinta Therapeutics, Inc.: Employee and Shareholder, Salary. J. Massey, Melinta Therapeutics, Inc.: Employee and Shareholder, Salary. M. Dudley, The Medicines Company: Employee, Salary.

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S250-S250
Author(s):  
Kanokporn Mongkolrattanothai ◽  
Leslie Stach ◽  
Regina Orbach

Abstract Background The rise of antimicrobial resistance among gram-negative (GN) pathogens has been dramatic nationally. Delayed initiation of active antimicrobial agents has been associated with poor outcomes. We aimed at evaluating the prevalence and treatment of multi-drug-resistant gram-negative (MDR-GN) bacteremia in our pediatric patients. Methods All episodes of GN bacteremia from 2017–2018 at our institution were retrospectively reviewed. GN defined as MDR in our study were carbapenem-resistant organisms (CRO), extended-spectrum β-lactamase (ESBL) producers, and GN that were resistant to cefepime and ≥2 classes of non-cephalosporin antimicrobial agents. Stenotrophomonas maltophilia was excluded. Ineffective empirical treatment (IET) is defined as an initial antibiotic regimen that is not active against the identified pathogen[s] based on in vitro susceptibility testing results. Results A total of 292 episodes of GN bacteremia were identified and 6 S. maltophilia were excluded. Of these, 29 bacteremic episodes in 26 patients were caused by MDR-GN organisms including 18 ESBL, 7 CRO, 1 ESBL and CRO, 3 non-ESBL/non-CRO cefepime-resistant MDR-GN. None of the CRO had carbapenemase genes detected. However, there was a patient with multiple sites of infection simultaneously with non-NDM CR Acinetobacter bacteremia and NDM-mediated CR-Klebsiella ventriculitis. The annual rate of MDR-GN bacteremia increased from 8% in 2017 to 12% in 2018. Almost half (48%) of episodes were community onset. Among these, all but one had underlying medical conditions with hospital exposure and most patients had central venous devices at the time of infection. 52% (15/29) episodes of MDR-GN bacteremia had IET. Despite IET, 47% (7/15) had negative blood cultures prior to initiation of effective therapy (6 ESBL and 1 P. aeruginosa). Various antibiotic regimens were used for CRO therapy as shown in Table 1. Conclusion In our institution, MDR-GN infection is increasing. As such, empiric meropenem is currently recommended in BMT or neutropenic patients with suspected sepsis. However, empiric meropenem must be used judiciously as its widely use will lead to more selection of MDR pathogens. It is essential to continue monitoring of these MDR-GN to guide appropriate empiric regimens. Disclosures All authors: No reported disclosures.


Author(s):  
Shalini Gupta ◽  
Pankaj Mandale

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.


Author(s):  
Roshni Agarwal ◽  
Vaibhav Agarwal ◽  
Anjali Tewari ◽  
Parwati Upadhyay

Background: Every time an antibiotic is used, whether appropriately or not, the probability of the development and spread of antibiotic resistant bacteria is increased. Thus, multidrug resistant bacteria particularly ESBL (Extended spectrum β­lactamase), Amp C and carbapenemases producing gram negative bacilli have emerged as a major health problem all over the world. Considering new treatment options as a carbapenems sparing and resistance prevention modality, this study was aimed to know the in vitro susceptibility pattern of Cefepime/Tazobactam (CPM/TZ) in comparison to other β-Lactam/ β-Lactamase inhibitors (BL/BLI) and carbapenems against GNB.Methods: A prospective study was conducted on all clinical samples received for a period of about 1 year. Identification and susceptibility of all isolates was done by Vitek 2 Compact system. Susceptibility of CPM/ TZ was done by disc diffusion method on the basis of CLSI guidelines. Both fermenters (E. coli and Klebsiella pneumoniae) and non-fermenters (Acintobacter baumanii and Pseudomonas aeruginosa) were included in the study.Results: Out of 550 GNB isolates the most common was E. coli (61.8%), Acintobacter baumanii (16%), Klebsiella pneumoniae (14.9%) and Pseudomonas aeruginosa (7.3%). Cefepime/tazobactam had a much higher susceptibility of 68% compared to cefepime (28%). Among the BL/BLI combinations tested cefepime/tazobactam (68%) showed the maximum percentage of susceptibility followed by cefoperazone/sulbactam (61.5%) and piperacillin/tazobactam (57.6%). Amongst all GNB isolates cefepime/tazobactam (68%) sensitivity was very much comparable to imipenem (71.8%) and meropenem (69.6%).Conclusions: CPM/TZ exhibited the best in vitro activity in comparison to the other BL/BLI. This new combination of cefepime/tazobactam appears to be a promising alternative therapeutic option to carbapenems. Clinical studies are needed to confirm this in vitro study result.


Author(s):  
Sachin H. Jain ◽  
Pradnya Joshi

Objective: The local anti-microbial susceptibility profile plays a very critical role in guiding clinicians to choose the appropriate empiric therapies. This study was conducted to assess the pathogen characteristics and the in vitro susceptibility of different Gram negative isolates to commonly used antibiotics in our hospital settings. Methods: A total of 110 Gram negative isolates were included in the study.  A retrospective, observational analysis of antibiogram data was performed for four antimicrobial agents including CSE-1034 (ceftriaxone-sulbactam-EDTA), piperacillin-tazobactam (pip-taz), cefoperazone-sulbactam and meropenem.  Results: Of the 200 clinical specimens analysed, Gram negative isolates obtained from 110 samples were included in the final analysis. The most common Gram negative isolates were Klebsiella species (35.5%), E. coli (33.6%) and P. aeruginosa (21.8%). The overall susceptibility was highest to CSE-1034 (100%) followed by meropenem (66.4%), cefoperazone-sulbactam (56.4%) and pip-taz (45.5%). The MIC90 range of CSE-1034 for Enterobacteriaceae was ≤0.5-≤4μg/ml and ≤2μg/ml for susceptible P. aeruginosa isolates. The MIC90 of meropenem for 94.4% of meropenem-susceptible Enterobacteriaceae strains was <0.25μg/ml and 64.3% of P. aeruginosa were having MIC ≤0.25μg/ml. The MIC90 of pip-taz for 82.5% of the pip-taz susceptible Enterobacteriaceae strains was 4μg/ml and 63.6% of P. aeruginosa was ≤8.0μg/ml. The MIC90 of cefoperazone-sulbactam susceptible strains were between ≤8 to ≤16μg/ml and 45.8% isolates of susceptible P. aeruginosa were having MIC between ≤8 to ≤16μg/ml. Conclusions: Overall, this in vitro surveillance study suggests that CSE-1034 can be considered an important therapeutic option for the treatment of various multi drug resistant Gram-negative bacterial infections and avert the threat of resistance to last resort antibiotics including carbapenems.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
D. Piérard ◽  
G. G. Stone

Abstract Background This antimicrobial surveillance study reports in vitro antimicrobial activity and susceptibility data for a panel of agents against respiratory isolates of Enterobacterales and Pseudomonas aeruginosa. Methods Isolates from respiratory specimens were collected in Africa/Middle East, Asia/South Pacific, Europe and Latin America between 2016 and 2018, as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) program. Broth microdilution methodology was used to quantify minimum inhibitory concentrations, from which rates of susceptibility were determined using EUCAST breakpoints (version 10). Rates of subsets with genes encoding β-lactamases (extended-spectrum β-lactamases [ESBLs], serine carbapenemases and metallo-β-lactamases [MBLs]) were also determined, as well as rates of multidrug-resistant (MDR) P. aeruginosa. Results Among all respiratory Enterobacterales isolates, susceptibility to ceftazidime-avibactam, meropenem, colistin and amikacin was ≥94.4% in each region. For Enterobacterales isolates that were ESBL-positive or carbapenemase-positive/MBL-negative, ceftazidime-avibactam susceptibility was 93.6 and 98.9%, respectively. Fewer than 42.7% of MBL-positive Enterobacterales isolates were susceptible to any agents, except colistin (89.0% susceptible). Tigecycline susceptibility was ≥90.0% among Citrobacter koseri and Escherichia coli isolates, including all β-lactamase-positive subsets. ESBL-positive Enterobacterales were more commonly identified in each region than isolates that were ESBL/carbapenemase-positive; carbapenemase-positive/MBL-negative; or MBL-positive. Among all respiratory P. aeruginosa isolates, the combined susceptibility rates (susceptible at standard dosing regimen plus susceptible at increased exposure) were highest to ceftazidime-avibactam, colistin and amikacin (≥82.4% in each region). Susceptibility to colistin was ≥98.1% for all β-lactamase-positive subsets of P. aeruginosa. The lowest rates of antimicrobial susceptibility were observed among MBL-positive isolates of P. aeruginosa (≤56.6%), with the exception of colistin (100% susceptible). MDR P. aeruginosa were most frequently identified in each region (18.7–28.7%), compared with the subsets of ESBL-positive; carbapenemase-positive/MBL-negative; or MBL-positive isolates. Conclusions Rates of susceptibility among the collections of respiratory Enterobacterales and P. aeruginosa isolates were highest to ceftazidime-avibactam, colistin and amikacin in each region. Tigecycline was active against all subsets of C. koseri and E. coli, and colistin was active against all subsets of P. aeruginosa. The findings of this study indicate the need for continued antimicrobial surveillance among respiratory Gram-negative pathogens, in particular those with genes encoding MBLs.


Pathogens ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1258
Author(s):  
Beniam Ghebremedhin ◽  
Parviz Ahmad-Nejad

In the last two decades, the worldwide dissemination of multidrug-resistant Gram-negative bacteria (MDR-GNB) has continued. Therapy options for such infections caused by MDR-GNB remain scarce, and only few new antimicrobial agents have been granted market approval. Cefiderocol has been approved for the treatment of infections associated with aerobic GNB with limited therapy options. This study evaluated the in vitro efficacy of cefiderocol against carbapenem-non-susceptible clinical GNB isolates from Germany. A total of 115 non-duplicate carbapenem-nonsusceptible GNB isolates, 61 (53.05%) of which were Enterobacterales species and 54 (46.95%) were non-fermenters (Acinetobacter baumanii and Pseudomonas aeruginosa), were investigated for their cefiderocol susceptibility. Minimum inhibitory concentrations (MICs) for cefiderocol were determined by disk diffusion, according to EUCAST (European committee for antimicrobial susceptibility testing). Susceptibility rates were based on EUCAST breakpoints. In the absence of a species-specific breakpoint, pharmacokinetic/-dynamic breakpoints were used. The most common pathogen was A. baumannii (33.91%), followed by Klebsiella pneumoniae (31.3%), P. aeruginosa (13.04%) and Escherichia coli (9.57%). Overall, 83.6% (51/61) of the Enterobacterales and 81.48% (44/54) of the non-fermenters were susceptible towards cefiderocol. In total, 20 species of Enterobacterales and non-fermenting GNB were resistant towards cefiderocol, irrespective of the isolation year (2014 to 2021). Moreover, the majority of the resistant isolates were among the OXA-23 producing A. baumannii (n = 7/26; 26.92%) from patients hospitalized during 2018 and 2019. Cefiderocol demonstrated high in vitro susceptibility rates against a wide range of carbapenem-non-susceptible GNB, including carbapenemase-producing isolates. Cefiderocol exhibited stability against hydrolysis by all carbapenemases, including metallo-β-lactamases (MBLs), except that few OXA-producing isolates exhibited resistance towards cefiderocol.


2019 ◽  
Vol 24 ◽  
pp. 2515690X1988627 ◽  
Author(s):  
Mekonnen Sisay ◽  
Negussie Bussa ◽  
Tigist Gashaw ◽  
Getnet Mengistu

Medicinal plants are targeted in the search for new antimicrobial agents. Nowadays, there is an alarmingly increasing antimicrobial resistance to available agents with a very slow development of new antimicrobials. It is, therefore, necessary to extensively search for new agents based on the traditional use of herbal medicines as potential source. The antibacterial activity of 80% methanol extracts of the leaves of Verbena officinalis (Vo-80ME), Myrtus communis (Mc-80ME), and Melilotus elegans (Me-80ME) was tested against 6 bacterial isolates using agar well diffusion technique. In each extract, 3 concentrations of 10, 20, and 40 mg/well were tested for each bacterium. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were also determined. Vo-80ME and Mc-80ME exhibited promising antibacterial activity against Staphylococcus aureus with the highest zone of inhibition being 18.67 and 26.16 mm, respectively at concentration of 40 mg/well. Regarding gram-negative bacteria, Vo-80ME exhibited an appreciable activity against Escherichia coli and Salmonella typhi. Mc-80ME displayed remarkable activity against all isolates including Pseudomonas aeruginosa with the maximum zone of inhibition being 22.83 mm. Me-80ME exhibited better antibacterial activity against E coli, but its secondary metabolites had little or no activity against other gram-negative isolates. The MIC values of Vo-80ME ranged from 0.16 to 4.00 mg/mL. The lowest MIC was observed in Mc-80ME, with the value being 0.032 mg/mL. Mc-80ME had bactericidal activity against all tested bacterial isolates. Mc-80ME showed remarkable zone of inhibitions in all tested bacterial isolates. Besides, Vo-80ME showed good antibacterial activity against S aureus, E coli, and S typhi. Conversely, Me-80ME has shown good activity against E coli only. Generally, M communis L and V officinalis have good MIC and MBC results.


Pathogens ◽  
2018 ◽  
Vol 7 (3) ◽  
pp. 75 ◽  
Author(s):  
Wadha Alfouzan ◽  
Rita Dhar ◽  
David Nicolau

Limited data are available on susceptibilities of these organisms to some of the recently made accessible antimicrobial agents. The in vitro activities of newer antibiotics, such as, ceftolozane/tazobactam (C/T) and ceftazidime/avibactam (CZA) along with some “older” antibiotics, for example fosfomycin (FOS) and colistin (CL) were determined against selected strains (resistant to ≥ 3 antimicrobial agents) of Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Minimum inhibitory concentrations (MIC) were determined by Clinical and Laboratory Standards Institute microbroth dilution. 133 isolates: 46 E. coli, 39 K. pneumoniae, and 48 P. aeruginosa were tested. Results showed that E. coli isolates with MIC50/90, 0.5/1 μ g / mL for CL; 4/32 μ g / mL for FOS; 0.25/32 μ g / mL for C/T; 0.25/8 μ g / mL for CZA, exhibited susceptibility rates of 95.7%, 97.8%, 76.1%, and 89.1%, respectively. On the other hand, K. pneumoniae strains with MIC50/90, 0.5/1 μ g / mL for CL; 256/512 μ g / mL for FOS; 2/128 μ g / mL for C/T; 0.5/128 μ g / mL for CZA showed susceptibility rates of 92.3%, 7.7%, 51.3%, and 64.1%, respectively. P. aeruginosa isolates with MIC50/90, 1/1 μ g / mL for CL; 128/128 μ g / mL for C/T; 32/64 μ g / mL for CZA presented susceptibility rates of 97.9%, 33.3%, and 39.6%, respectively. Higher MICs were demonstrated against most of the antibiotics. However, CL retained efficacy at low MICs against most of the isolates tested.


Author(s):  
Yi-Hsuan Lee ◽  
Chao-Min Wang ◽  
Po-Yu Liu ◽  
Ching-Chang Cheng ◽  
Zong-Yen Wu ◽  
...  

Essential oils from the dried spikes ofNepeta tenuifolia(Benth) are obtained by steam distillation. Pulegone was identified as the main component in the spikes ofN. tenuifoliathrough analysis, with greater than 85% purity obtained in this study. The essential oils are extremely active against all Gram-positive and some Gram-negative reference bacteria, particularlySalmonella enterica,Citrobacter freundii, andEscherichia coli. The minimum inhibitory concentration was found to be between 0.08 and 0.78% (againstS. enterica), 0.39 and 0.78% (againstC. freundii), and 0.097 and 0.39% (againstE. coli), whereas the minimum bactericidal concentration varied in range from 0.097% to 1.04%. In general, the essential oils show a strong inhibitory action against all tested reference strains and clinical isolates. However, the antibacterial activity of EOs against bothPseudomonas aeruginosareference strains and clinical isolates was relatively lower than other Gram-negative pathogens. The essential oils ofN. tenuifoliaalso displayed bactericidal activities (MBC/MIC < 4) in this study. These findings reflect the bactericidal activity of the essential oils against a wide range of multidrug-resistant clinical pathogens in an in vitro study. In addition, we propose the fragmentation pathways of pulegone and its derivatives by LC-ESI-MS/MS in this study.


2021 ◽  
Vol 33 (7) ◽  
pp. 1525-1529
Author(s):  
Parmesh Kumar Dwivedi ◽  
Devdutt Chaturvedi

A new series of fluorinated sulfur inserted benzimidazole analogues Za-i were synthesized and characterized. The new compounds were screened for their antimicrobial and antioxidant potential. The synthesized compounds were obtained by multiple step synthesis, initiating from the synthesis of 5-(difluoromethoxy)-1H-benzimidazole-2-thiol X. The compounds Ya-i prepared by reacting differently substituted anilines with chloroacetylchloride and triethylamine in DMF. Finally, the compound X was reacted with different derivatives of 2-chloro-N-phenylacetamide resulting in formation of titled compounds Za-i. The synthesized compounds (Za-Zi) were characterized by spectral analysis viz.1H & 13C NMR, mass spectra, elemental analysis and IR. The in vitro antimicrobial potential against Gram-positive (S. aureus and E. faecalis) and Gram-negative bacterial (E. coli and P.aeruginosa) strains as well as fungi (A. niger and C. albicans) was recorded for the obtained compounds. Some of the compounds exhibited encouraging results (in MIC) against Gram-positive and Gram-negative bacterial strains. These studies thus suggest that the designed sulfur inserted fluoro-benzimidazoles scaffold may serve as new promising template for further amplification as antimicrobial agents.


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