scholarly journals Evaluation of Current Activities of Fluoroquinolones against Gram-Negative Bacilli Using Centralized In Vitro Testing and Electronic Surveillance

2001 ◽  
Vol 45 (1) ◽  
pp. 267-274 ◽  
Author(s):  
Daniel F. Sahm ◽  
Ian A. Critchley ◽  
Laurie J. Kelly ◽  
James A. Karlowsky ◽  
David C. Mayfield ◽  
...  

ABSTRACT Given the propensity for Enterobacteriaceae and clinically significant nonfermentative gram-negative bacilli to acquire antimicrobial resistance, consistent surveillance of the activities of agents commonly prescribed to treat infections arising from these organisms is imperative. This study determined the activities of two fluoroquinolones, levofloxacin and ciprofloxacin, and seven comparative agents against recent clinical isolates ofEnterobacteriaceae, Pseudomonas aeruginosa,Acinetobacter baumannii, and Stenotrophomonas maltophilia using two surveillance strategies: 1) centralized in vitro susceptibility testing of isolates collected from 27 hospital laboratories across the United States and 2) analysis of data from The Surveillance Network Database-USA, an electronic surveillance network comprising more than 200 laboratories nationwide. Regardless of the surveillance method, Enterobacteriaceae,P. aeruginosa, and A. baumannii demonstrated similar rates of susceptibility to levofloxacin and ciprofloxacin. Susceptibilities to the fluoroquinolones approached or exceeded 90% for all Enterobacteriaceae except Providenciaspp. (≤65%). Approximately 70% of P. aeruginosa and 50% of A. baumanii isolates were susceptible to both fluoroquinolones. Among S. maltophilia isolates, 50% more isolates were susceptible to levofloxacin than to ciprofloxacin. Overall, the rate of ceftazidime nonsusceptibility amongEnterobacteriaceae was 8.7%, with fluoroquinolone resistance rates notably higher among ceftazidime-nonsusceptible isolates than ceftazidime-susceptible ones. Multidrug-resistant isolates were present among all species tested but were most prevalent for Klebsiella pneumoniae andEnterobacter cloacae. No gram-negative isolates resistant only to a fluoroquinolone were encountered, regardless of species. Thus, while levofloxacin and ciprofloxacin have maintained potent activity against Enterobacteriaceae, the potential for fluoroquinolone resistance, the apparent association between fluoroquinolone and cephalosporin resistance, and the presence of multidrug resistance in every species examined emphasize the need to maintain active surveillance of resistance patterns among gram-negative bacilli.

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S733-S733
Author(s):  
Dee Shorttidge ◽  
Jennifer M Streit ◽  
Michael D Huband ◽  
Robert K Flamm

Abstract Background Delafloxacin (DLX) is an anionic fluoroquinolone (FQ) that has been approved in the United States and in Europe for the treatment of acute bacterial skin and skin structure infections and was recently approved in the US for treatment of community-acquired bacterial pneumonia (CABP). In the present study, in vitro susceptibility (S) results for DLX and comparator agents were determined for CABP pathogens including Streptococcus pneumoniae (SPN), Haemophilus influenzae (HI), H. parainfluenzae (HP) and Moraxella catarrhalis (MC) clinical isolates from European hospitals participating in the SENTRY Program during 2014-2019. Methods A total of 2,835 SPN, 1,484 HI, 959 MC, and 20 HP isolates were collected from community-acquired respiratory tract infections (CARTI) during 2014-2019 from European hospitals. Sites included only 1 isolate/patient/infection episode. Isolate identifications were confirmed at JMI Laboratories. Susceptibility testing was performed according to CLSI broth microdilution methodology, and EUCAST (2020) breakpoints were applied where applicable. Other antimicrobials tested included levofloxacin (LEV) and moxifloxacin (MOX; not tested in 2015). Multidrug-resistant (MDR) SPN isolates were categorized as being nonsusceptible (NS) to amoxicillin-clavulanate, erythromycin (ERY), and tetracycline; other SPN phenotypes were ERY-NS, or penicillin (PEN)-NS. β-lactamase (BL) presence was determined for HI, HP, and MC. Results The activities of the 3 FQs are shown in the table. The most active agent against SPN was DLX, with the lowest MIC50/90 values of 0.015/0.03 mg/L. DLX activities were the same when tested against the MDR or PEN-NS for SPN phenotypes. ERY-NS isolates had DLX MIC50/90 results of 0.015/0.03 mg/L. DLX was the most active FQ against HI, HP, and MC. BL presence did not affect FQ MIC values for HI or MC; only 1 HP isolate was BL-positive. Conclusion DLX demonstrated potent in vitro antibacterial activity against SPN, HI, HP, and MC. DLX was active against MDR SPN that were NS to the agents commonly used as treatments for CABP. These data support the utility of DLX in CABP including when caused by antibiotic resistant strains. Table 1 Disclosures 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) Robert K. Flamm, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)


2001 ◽  
Vol 45 (4) ◽  
pp. 1037-1042 ◽  
Author(s):  
Daniel F. Sahm ◽  
James A. Karlowsky ◽  
Laurie J. Kelly ◽  
Ian A. Critchley ◽  
Mark E. Jones ◽  
...  

ABSTRACT Although changing patterns in antimicrobial resistance inStreptococcus pneumoniae have prompted several surveillance initiatives in recent years, the frequency with which these studies are needed has not been addressed. To approach this issue, the extent to which resistance patterns change over a 1-year period was examined. In this study we analyzed S. pneumoniaeantimicrobial susceptibility results produced in our laboratory with isolates obtained over 2 consecutive years (1997–1998 and 1998–1999) from the same 96 institutions distributed throughout the United States. Comparison of results revealed increases in resistant percentages for all antimicrobial agents studied except vancomycin. For four of the agents tested (penicillin, cefuroxime, trimethoprim-sulfamethoxazole, and levofloxacin), the increases were statistically significant (P < 0.05). Resistance to the fluoroquinolone remained low in both years (0.1 and 0.6%, respectively); in contrast, resistance to macrolides was consistently greater than 20%, and resistance to trimethoprim-sulfamethoxazole increased from 13.3 to 27.3%. Multidrug resistance, concurrent resistance to three or more antimicrobials of different chemical classes, also increased significantly between years, from 5.9 to 11%. The most prevalent phenotype was resistance to penicillin, azithromycin (representative macrolide), and trimethoprim-sulfamethoxazole. Multidrug-resistant phenotypes that included fluoroquinolone resistance were uncommon; however, two phenotypes that included fluoroquinolone resistance not found in 1997–1998 were encountered in 1998–1999. This longitudinal surveillance study of resistance inS. pneumoniae revealed that significant changes do occur in just a single year and supports the need for surveillance at least on an annual basis, if not continuously.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S577-S578
Author(s):  
Dee Shortridge ◽  
Jennifer M Streit ◽  
Michael D Huband ◽  
Robert K Flamm

Abstract Background Delafloxacin (DLX) is an anionic fluoroquinolone (FQ) antimicrobial that was approved in 2017 by the United States (US) Food and Drug Administration for the treatment of acute bacterial skin and skin structure infections. DLX recently successfully completed a clinical trial for the treatment of community-acquired bacterial pneumonia (CABP). In the present study, in vitro susceptibility (S) results for DLX and comparator agents were determined for CABP pathogens including Streptococcus pneumoniae (SPN), Haemophilus influenzae (HI), H. parainfluenzae (HP) and Moraxella catarrhalis (MC) clinical isolates from US hospitals participating in the SENTRY Program during 2014–2018. Methods A total of 1,975 SPN, 1,128 HI, 684 MC, and 43 HP isolates were collected from community-acquired respiratory tract infections (CARTI) during 2014–2018 from US hospitals. Sites included only 1 isolate/patient/infection episode. Isolate identifications were confirmed at JMI Laboratories. Susceptibility testing was performed according to CLSI broth microdilution methodology, and CLSI (2019) breakpoints were applied where applicable. Other antimicrobials tested included levofloxacin (LEV) and moxifloxacin (MOX; not tested in 2015). Multidrug-resistant (MDR) SPN isolates were categorized as being nonsusceptible (NS) to amoxicillin-clavulanate, erythromycin, and tetracycline; other SPN phenotypes were LEV-NS or penicillin (PEN)-NS. β-Lactamase (BL) presence was determined for HI, HP, and MC. Results The activities of the 3 FQs are shown in the table. The most active agent against SPN was DLX, with the lowest MIC50/90 values of 0.015/0.03 mg/L. DLX activities were similar when tested against the MDR or PEN-NS for SPN phenotypes. LEV-NS isolates had DLX MIC50/90 results of 0.12/0.25 mg/L. DLX was the most active FQ against HI, HP, and MC. BL presence did not affect FQ MIC values for HI or MC; only 2 HP isolates were BL-positive. Conclusion DLX demonstrated potent in vitro antibacterial activity against SPN, HI, HP, and MC. DLX was active against MDR SPN that were NS to the agents commonly used as treatments for CABP. DLX had excellent activity against LEV-NS SPN. These data support the continued study of DLX as a potential treatment for CABP. Disclosures All authors: No reported disclosures.


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.


2016 ◽  
Vol 19 (4) ◽  
pp. 448 ◽  
Author(s):  
Katie E. Barber ◽  
Jessica K. Ortwine ◽  
Ronda L Akins

Purpose: Gram-negative resistance continues to rise with treatment options becoming more limited. Ceftazidime/avibactam was recently approved in the United States and Europe, which combines an established third-generation cephalosporin with a new, unique, non-β-lactam β-lactamase inhibitor. This review conducts a thorough examination of structure, pharmacology, spectrum of activity, pharmacokinetics/pharmacodynamics, in vitro and clinical efficacy and safety/tolerability of ceftazidime/avibactam, as well as detailed future directions for the agent. Methods: Pubmed and clinicaltrials.gov searches, as well as abstracts from the 2015 Interscience Conference on Antimicrobial Agents and Chemotherapy/International Society of Chemotherapy (ICAAC/ICC) and ID Week meetings and the 2016 American Society of Microbiology Microbe meeting, were conducted from January 2004 – September 2016. Relevant search terms included ceftazidime, ceftazidime/avibactam, avibactam, NXL104 and AVE1330A. The US package insert for ceftazidime/avibactam (02/2015) and European public assessment report (06/2016) were also reviewed. Results: In vitro susceptibility for ceftazidime/avibactam displayed potent activity against many Enterobacteriaceae including extended-spectrum-β-lactamase (ESBL) and carbapenemase-producing strains, as well as Pseudomonas aeruginosa. Phase II clinical trials utilized for approval demonstrated comparable safety and efficacy to imipenem/cilistatin for treatment of complicated urinary tract infections (70.4% vs. 71.4%) and combined with metronidazole compared to meropenem in complicated intra-abdominal infections (91.2% vs 93.4%). Phase III data displayed non-inferior efficacy of ceftazidime/avibactam compared to doripenem for complicated urinary tract infections (70.2% vs 66.2%) and combined with metronidazole compared to meropenem in complicated intra-abdominal infections (82.5% vs 84.9%), as well as comparable safety. Ceftazidime/avibactam was well-tolerated but does require renal adjustments. Additionally, 3 case series and a single case report have demonstrated the potential for ceftazidime/avibactam against multidrug resistant organisms for compassionate use or failure after previous therapy. Conclusion: By adding avibactam to ceftazidime, clinicians’ antimicrobial armamentarium is expanded, potentially increasing the ability to combat multi-drug resistant gram-negative pathogens, particularly ESBL and carbapenemase-producing organisms, as well as Pseudomonas aeruginosa. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.


2019 ◽  
Vol 6 (6) ◽  
Author(s):  
Dee Shortridge ◽  
Michael A Pfaller ◽  
S J Ryan Arends ◽  
Janet Raddatz ◽  
Daryl D DePestel ◽  
...  

Abstract Background Pseudomonas aeruginosa remains an important cause of hospital-acquired infections in the United States and is frequently multidrug-resistant (MDR). The Infectious Diseases Society of America guidelines recommend empiric combination therapy that includes an antipseudomonal β-lactam with an aminoglycoside or fluoroquinolone likely to cover ≥95% of P. aeruginosa infections in seriously ill patients at risk of having an MDR pathogen. Ceftolozane is an antipseudomonal cephalosporin, combined with the β-lactamase inhibitor tazobactam. Ceftolozane-tazobactam is approved for treatment of complicated urinary tract infections and complicated intra-abdominal infections. A phase 3 clinical trial for the treatment of hospital-acquired pneumonia including ventilator-associated pneumoniae was recently completed. We compared the in vitro susceptibility rate of ceftolozane-tazobactam with the cumulative susceptibility rates of antibiotic combinations commonly used against P. aeruginosa. Methods Isolates were collected from intensive care unit patients hospitalized in 32 US hospitals from 2011 to 2017. The susceptibilities of 1543 P. aeruginosa isolates from bloodstream infections (198 isolates, 12.8%) or pneumonia (1345 isolates, 87.2%) were determined for ceftolozane-tazobactam and comparators. Results The most active antimicrobials were colistin (99.4% susceptible), amikacin (98.1% susceptible), and ceftolozane-tazobactam (96.5% susceptible). The susceptibilities to other antipseudomonal β-lactams and fluoroquinolones were &lt;84%. A cumulative susceptibility of ≥95% was reached for cefepime, ceftazidime, meropenem, and piperacillin-tazobactam only in combination with amikacin due to the lower susceptibilities of gentamicin, ciprofloxacin, and levofloxacin. Monotherapies that exceeded 95% were ceftolozane-tazobactam, amikacin, and colistin. Conclusions Ceftolozane-tazobactam monotherapy is likely to be active against more isolates than a combination of another β-lactam and a fluoroquinolone or gentamicin for serious P. aeruginosa infections.


2017 ◽  
Vol 61 (12) ◽  
Author(s):  
Barbara A. Brown-Elliott ◽  
Richard J. Wallace

ABSTRACT There is a paucity of efficacious antimicrobials (especially oral) against clinically relevant species of Nocardia. To date, all species of Nocardia have been susceptible to linezolid, the first commercially available oxazolidinone. Tedizolid is a new oxazolidinone with previously reported improved in vitro and in vivo (intracellular) potency against multidrug-resistant strains of Mycobacterium sp. and Nocardia brasiliensis. Using the current Clinical and Laboratory Standards Institute-recommended broth microdilution method, 101 isolates of Nocardia spp., including 29 Nocardia cyriacigeorgica, 17 Nocardia farcinica, 13 Nocardia nova complex, 21 Nocardia brasiliensis, 5 Nocardia pseudobrasiliensis, and 5 Nocardia wallacei isolates and 11 isolates of less common species, were tested for susceptibility to tedizolid and linezolid. For the most common clinically significant species of Nocardia, tedizolid MIC50 values were 0.25 μg/ml for N. nova complex, N. brasiliensis, N. pseudobrasiliensis, and N. wallacei, compared to linezolid MIC50 values of 1, 2, 0.5, and 1 μg/ml, respectively. Tedizolid and linezolid MIC90 values were 2 μg/ml for N. nova complex and N. brasiliensis. Tedizolid MIC50 and MIC90 values for both N. cyriacigeorgica and N. farcinica were 0.5 μg/ml and 1 μg/ml, respectively, compared to linezolid MIC50 and MIC90 values of 2 and 4 μg/ml, respectively. Based on MIC90 values, this study showed that tedizolid was 2- to 3-fold more active than linezolid in vitro against most common species of Nocardia, with the exception of the N. nova complex and N. brasiliensis, for which values were the same. These results may warrant evaluation of tedizolid as a potential treatment option for Nocardia infections.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kuan-Jen Chen ◽  
Ming-Hui Sun ◽  
Chiun-Ho Hou ◽  
Hung-Chi Chen ◽  
Yen-Po Chen ◽  
...  

AbstractBacterial endophthalmitis is a rare intraocular infection, and prompt administration of intravitreal antibiotics is crucial for preventing severe vision loss. The retrospective study is to investigate the in vitro susceptibility to the antibiotics vancomycin, amikacin, and ceftazidime of bacterial endophthalmitis isolates in specimens at a tertiary referral center from January 1996 to April 2019 in Taiwan. Overall, 450 (49.9%) isolates were Gram positive, 447 (49.6%) were Gram negative, and 4 (0.4%) were Gram variable. In Gram-positive isolates, coagulase-negative staphylococci were the most commonly cultured bacteria (158, 35.1%), followed by Streptococci (100, 22.2%), Enterococci (75, 16.7%), and Staphylococcus aureus (70, 15.6%). In Gram-negative isolates, they were Klebsiella pneumoniae (166, 37.1%) and Pseudomonas aeruginosa (131, 29.3%). All Gram-positive organisms were susceptible to vancomycin, with the exception of one Enterococcus faecium isolate (1/450, 0.2%). Of the Gram-negative isolates, 96.9% and 93.7% were susceptible to ceftazidime and amikacin, respectively. Nine isolates (9/447, 2.0%) were multidrug-resistant Gram-negative bacteria, comprising K. pneumoniae (4/164, 2.4%), Acinetobacter baumannii (2/3, 67%), and Stenotrophomonas maltophilia (3/18, 17%). In conclusion, in vitro susceptibility testing revealed that vancomycin remains the suitable antibiotic treatment for Gram-positive endophthalmitis. Ceftazidime and amikacin provide approximately the same degree of Gram-negative coverage. Multidrug-resistant bacterial endophthalmitis was uncommon.


2021 ◽  
Author(s):  
Kuan-Jen Chen ◽  
Ming-Hui Sun ◽  
Chiun-Ho Hou ◽  
Hung-Chi Chen ◽  
Yen-Po Chen ◽  
...  

Abstract Bacterial endophthalmitis is a rare intraocular infection, and prompt administration of intravitreal antibiotics is crucial for preventing severe vision loss. The retrospective study is to investigate the in vitro susceptibility to the antibiotics vancomycin, amikacin, and ceftazidime of bacterial endophthalmitis isolates in specimens at a tertiary referral center from January 1996 to April 2019 in Taiwan. Overall, 450 (49.9%) isolates were gram positive, 447 (49.6%) were gram negative, and 4 (0.4%) were gram variable. In gram-positive isolates, coagulase-negative staphylococci were the most commonly cultured bacteria (158, 35.1%), followed by streptococci (100, 22.2%), enterococci (75, 16.7%), and Staphylococcus aureus (70, 15.6%). In gram-negative isolates, they were Klebsiella pneumoniae (166, 37.1%) and Pseudomonas aeruginosa (131, 29.3%). All gram-positive organisms were susceptible to vancomycin, with the exception of one Enterococcus faecium isolate (1/450, 0.2%). Of the gram-negative isolates, 96.9% and 93.7% were susceptible to ceftazidime and amikacin, respectively. Nine isolates (9/447, 2.0%) were multidrug-resistant gram-negative bacteria, comprising Klebsiella pneumoniae (4/164, 2.4%), Acinetobacter baumannii (2/3, 67%), and Stenotrophomonas maltophilia (3/18, 17%). In conclusion, in vitro susceptibility testing revealed that vancomycin remains the suitable antibiotic treatment for gram-positive endophthalmitis. Ceftazidime and amikacin provide approximately the same degree of gram-negative coverage. Multidrug-resistant bacterial endophthalmitis was uncommon.


Chemotherapy ◽  
2014 ◽  
Vol 60 (3) ◽  
pp. 151-156 ◽  
Author(s):  
Sezen Özkök ◽  
Turhan Togan ◽  
Ayşegül Yesilkaya ◽  
Funda Timurkaynak ◽  
Özlem Kurt Azap ◽  
...  

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