scholarly journals Impact of Tigecycline’s MIC in the Outcome of Critically Ill Patients with Carbapenemase-Producing Klebsiella pneumoniae Bacteraemia Treated with Tigecycline Monotherapy—Validation of 2019′s EUCAST Proposed Breakpoint Changes

Antibiotics ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 828
Author(s):  
Matthaios Papadimitriou-Olivgeris ◽  
Christina Bartzavali ◽  
Alexandra Nikolopoulou ◽  
Fevronia Kolonitsiou ◽  
Virginia Mplani ◽  
...  

Background: Tigecycline is a therapeutic option for carbapenemase-producing Klebsiella pneumoniae (CP-Kp). Our aim was to evaluate the impact of the tigecycline’s minimum inhibitory concentration (MIC) in the outcome of patients with CP-Kp bacteraemia treated with tigecycline monotherapy. Methods: Patients with monomicrobial bacteraemia due to CP-Kp that received appropriate targeted monotherapy or no appropriate treatment were included. Primary outcome was 30-day mortality. MICs of meropenem, tigecycline, and ceftazidime/avibactam were determined by Etest, whereas for colistin, the broth microdilution method was applied. PCR for blaKPC, blaVIM, blaNDM, and blaOXA genes was applied. Results: Among 302 CP-Kp bacteraemias, 32 isolates (10.6%) showed MICs of tigecycline ≤ 0.5 mg/L, whereas 177 (58.6%) showed MICs that were 0.75–2 mg/L. Colistin and aminoglycoside susceptibility was observed in 43.0% and 23.8% of isolates, respectively. The majority of isolates carried blaKPC (249; 82.5%), followed by blaVIM (26; 8.6%), both blaKPC and blaVIM (16; 5.3%), and blaNDM (11; 3.6%). Fifteen patients with tigecycline MIC ≤ 0.5 mg/L and 55 with MIC 0.75–2 mg/L were treated with tigecycline monotherapy; 30-day mortality was 20.0% and 50.9%, respectively (p = 0.042). Mortality of 150 patients that received other antimicrobials was 24.7%; among 82 patients that received no appropriate treatment, mortality was 39.0%. No difference in 30-day mortality was observed between patients that received tigecycline (MIC ≤ 0.5 mg/L) or other antimicrobials. Conclusion: Tigecycline monotherapy was as efficacious as other antimicrobials in the treatment of bloodstream infections due to CP-Kp isolates with a tigecycline’s MIC ≤ 0.5 mg/L.

Antibiotics ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 76
Author(s):  
Matthaios Papadimitriou-Olivgeris ◽  
Christina Bartzavali ◽  
Alexandra Georgakopoulou ◽  
Fevronia Kolonitsiou ◽  
Chrisavgi Papamichail ◽  
...  

Background: The increased frequency of bacteraemias caused by pandrug-resistant Klebsiella pneumoniae (PDR-Kp) has significant implications. The aim of the present study was to identify predictors associated with mortality of PDR-Kp bacteraemias. Methods: Patients with monomicrobial bacteraemia due to PDR-Kp were included. K. pneumoniae was considered PDR if it showed resistance to all available groups of antibiotics. Primary outcome was 30-day mortality. Minimum inhibitory concentrations (MICs) of meropenem, tigecycline, fosfomycin, and ceftazidime/avibactam were determined by Etest, whereas for colistin, the broth microdilution method was applied. blaKPC, blaVIM, blaNDM, and blaOXA genes were detected by PCR. Results: Among 115 PDR-Kp bacteraemias, the majority of infections were primary bacteraemias (53; 46.1%), followed by catheter-related (35; 30.4%). All isolates were resistant to tested antimicrobials. blaKPC was the most prevalent carbapenemase gene (98 isolates; 85.2%). Thirty-day mortality was 39.1%; among 51 patients with septic shock, 30-day mortality was 54.9%. Multivariate analysis identified the development of septic shock, Charlson comorbidity index, and bacteraemia other than primary or catheter-related as independent predictors of mortality, while a combination of at least three antimicrobials was identified as an independent predictor of survival. Conclusions: Mortality of PDR-Kp bloodstream infections was high. Administration of at least three antimicrobials might be beneficial for infections in critically ill patients caused by such pathogens.


Author(s):  
Borel Bisso Ndezo ◽  
Christian Ramsès Tokam Kuaté ◽  
Jean Paul Dzoyem

Background. Thymol and piperine are two naturally occurring bioactive compounds with several pharmacological activities. In this study, their antibiofilm potential either alone or in combination with three aminoglycoside antibiotics was evaluated against a biofilm of Klebsiella pneumoniae. Methods. Determination of antimicrobial susceptibility was performed using the broth microdilution method. Biofilm formation was evaluated by the microtiter plate method. Antibiofilm activity was determined using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium-bromide (MTT) assay. The combination studies were performed by the checkerboard microdilution method. Results. The minimum biofilm inhibitory concentration (MBIC) of streptomycin was reduced by 16- to 64-fold when used in combination with thymol, while the MBIC of kanamycin was reduced by 4-fold when combined with piperine. The minimum biofilm eradication concentration (MBEC) values of streptomycin, amikacin, and kanamycin were, respectively, 16- to 128-fold, 4- to 128-fold, and 8- to 256-fold higher than the planktonic minimum inhibitory concentration (MIC). Thymol combined with streptomycin or kanamycin showed synergic effects against the preformed biofilm with 16- to 64-fold reduction in the minimum biofilm eradication concentration values of each antibiotic in combination. Piperine acted also synergically with kanamycin with an 8- to 16-fold reduction in the minimum biofilm eradication concentration values of kanamycin in combination. Conclusion. The association of thymol with antibiotics showed a strong synergistic effect both in the inhibition of biofilm formation and the destruction of the preformed biofilm of K. pneumoniae. This study suggests that a combination of thymol with streptomycin, amikacin, or kanamycin could be a promising alternative therapy to overcome the problem of K. pneumoniae biofilm-associated infections.


2021 ◽  
Vol 8 ◽  
Author(s):  
Shuzhen Xiao ◽  
Tianchi Chen ◽  
Hairu Wang ◽  
Qian Zeng ◽  
Qing Chen ◽  
...  

Background: Bloodstream infections (BSIs) are recognized as important nosocomial infections. Klebsiella pneumoniae is one of the major causes of bacteremia. This retrospective study focused on drug susceptibility and molecular epidemiology of K. pneumoniae isolated from intensive care unit (ICU) patients with BSI in Shanghai, China.Methods: Consecutive K. pneumoniae isolates were collected from ICU patients. Antibiotic susceptibility testing was conducted by the broth microdilution method. PCR was performed to detect antimicrobial resistance genes. We also completed multilocus sequence typing (MLST) and GoeBURST was used to analyze the result of MLST.Results: A total of 78 K. pneumoniae isolates were enrolled. K. pneumoniae from ICU-BSIs were highly resistant to almost all common antibiotics. The most frequent resistance determinants responsible for extended-spectrum β-lactamase (ESBL) producers were blaCTX−M−14, blaCTX−M−15, and blaCTX−M−55. KPC was the only enzyme, which was detected by the carbapenemase producers. The most principal sequence types (STs) were ST11, ST15, and ST23.Conclusion: This study presents for the first time the antibiotic resistance phenotype and molecular epidemiology of K. pneumoniae isolated from ICU patients with BSIs in Shanghai. ICU-BSI K. pneumoniae is characteristic of a high resistance rate. The occurrence of the KPC-2 enzyme may result from nosocomial clonal dissemination of ST11 K. pneumoniae.


2020 ◽  
Author(s):  
Shuzhen Xiao ◽  
Tianchi Chen ◽  
Hairu Wang ◽  
Qing Chen ◽  
Feifei Gu ◽  
...  

Abstract Background Bloodstream infections (BSIs) are always associated with increased cost, prolonged hospitalization and higher mortality, especially for patients in intensive care units (ICUs). Klebsiella pneumoniae is recognized as the major cause of bacteremia around the world and resistant to most clinically significant antibiotics. This retrospective study focused on drug susceptibility and molecular epidemiology of K. pneumoniae isolated from ICU patients with BSI in Shanghai, China.Methods Consecutive K. pneumoniae isolates were collected from ICU patients with bacteremia in Shanghai from January 2016 to December 2019. Antibiotic susceptibility testing and primary screening test for extended-spectrum β-lactamase (ESBL) and carbapenemase production were conducted by broth microdilution method. Polymerase chain reaction (PCR) was performed to detect antimicrobial resistance genes and to confirm carbapenemase production. We also conducted multilocus sequence typing (MLST), of which the result was analyzed by GoeBURST.Results A total of 78 K. pneumoniae isolates were enrolled. K. pneumoniae isolated from ICU bloodstream infections (ICU-BSIs) were highly resistant to almost all clinically common antibiotics, except for colistin (11.5%) and tigecycline (23.0%). ESBL-producing and carbapenemase-producing K. pneumoniae accounted for 74.4% and 71.7%, respectively. The most frequently found genotype in ESBL producers was blaCTX−M−14 (44/58, 75.9%), followed by blaCTX−M−15 (15/58, 25.9%) and blaCTX−M−55 (8/58, 13.8%). KPC is the only enzyme generated by carbapenemase producers and all KPC enzymes were encoded by blaKPC−2. The most principal ST was ST11 (50/78, 64.1%), followed by ST15 (7/78, 9.0%) and ST23 (3/78, 3.8%). Two newfound sequence types were identified in our study.Conclusions This study is the first to demonstrate the antibiotic resistance phenotype and molecular epidemiology of K. pneumoniae isolated from ICU patients with bloodstream infections in Shanghai. It is noteworthy that ICU-BSI K. pneumoniae is characteristic of high resistance rate. According to the consequence of resistance gene detection and MLST analysis, the prevalence of KPC-2 enzyme may result from nosocomial clonal dissemination of ST11 K. pneumoniae.


2015 ◽  
Vol 59 (6) ◽  
pp. 3059-3065 ◽  
Author(s):  
C. Pitart ◽  
F. Marco ◽  
T. A. Keating ◽  
W. W. Nichols ◽  
J. Vila

ABSTRACTCeftazidime-avibactam and comparator antibiotics were tested by the broth microdilution method against 200Enterobacteriaceaeand 25Pseudomonas aeruginosastrains resistant to fluoroquinolones (including strains with the extended-spectrum β-lactamase [ESBL] phenotype and ceftazidime-resistant strains) collected from our institution. The MICs and mechanisms of resistance to fluoroquinolone were also studied. Ninety-nine percent of fluoroquinolone-resistantEnterobacteriaceaestrains were inhibited at a ceftazidime-avibactam MIC of ≤4 mg/liter (using the susceptible CLSI breakpoint for ceftazidime alone as a reference). Ceftazidime-avibactam was very active against ESBLEscherichia coli(MIC90of 0.25 mg/liter), ESBLKlebsiella pneumoniae(MIC90of 0.5 mg/liter), ceftazidime-resistant AmpC-producing species (MIC90of 1 mg/liter), non-ESBLE. coli(MIC90of ≤0.125 mg/liter), non-ESBLK. pneumoniae(MIC90of 0.25 mg/liter), and ceftazidime-nonresistant AmpC-producing species (MIC90of ≤0.5 mg/liter). Ninety-six percent of fluoroquinolone-resistantP. aeruginosastrains were inhibited at a ceftazidime-avibactam MIC of ≤8 mg/liter (using the susceptible CLSI breakpoint for ceftazidime alone as a reference), with a MIC90of 8 mg/liter. Additionally, fluoroquinolone-resistant mutants from each species tested were obtainedin vitrofrom two strains, one susceptible to ceftazidime and the other a β-lactamase producer with a high MIC against ceftazidime but susceptible to ceftazidime-avibactam. Thereby, the impact of fluoroquinolone resistance on the activity of ceftazidime-avibactam could be assessed. The MIC90values of ceftazidime-avibactam for the fluoroquinolone-resistant mutant strains ofEnterobacteriaceaeandP. aeruginosawere ≤4 mg/liter and ≤8 mg/liter, respectively. We conclude that the presence of fluoroquinolone resistance does not affectEnterobacteriaceaeandP. aeruginosasusceptibility to ceftazidime-avibactam; that is, there is no cross-resistance.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S92-S92
Author(s):  
Melissa White ◽  
Kerry Lenzi ◽  
Lauren S Dutcher ◽  
Stephen Saw ◽  
Steven C Morgan ◽  
...  

Abstract Background The Clinical and Laboratory Standards Institute reduced the levofloxacin minimum inhibitory concentration (MIC) breakpoint from ≤2 to ≤0.5 mg/L for Enterobacteriaceae in 2019 guidelines. The reduction is based on Monte Carlo simulations for a levofloxacin dose of 750 mg daily. The aim of this study was to determine whether there was a difference in clinical outcomes in the treatment of Enterobacteriaceae bacteremia with levofloxacin step-down therapy retrospectively comparing patients with isolates with low levofloxacin MICs (≤0.5 mg/L) to high MICs (1–2 mg/L). Methods This retrospective, two-center cohort study included patients ≥18 years of age with a monomicrobial Enterobacteriaceae bacteremia with a levofloxacin MIC ≤2 mg/L from March 2017 through December 2018. Patients had to have received treatment with ≥3 days of levofloxacin step-down therapy, initial intravenous therapy with an agent active against the isolated organism, and total duration not exceeding 16 days from first negative blood culture. A subset of patients whose isolates had low levofloxacin MICs were randomly selected for comparison to all patients with high levofloxacin MICs in a 3:1 ratio. The primary outcome was a composite endpoint of recurrence and mortality within 30 days of completion of the antibiotic course. Secondary outcomes included post-culture length of stay (LOS) and 30-day readmission rate. Results Thirty-three patients with high MIC and 99 with low MIC were included. Urinary source was predominant and occurred in 44% of patients, and Escherichia coli was the infecting organism in 48%. Over 80% of patients experienced source resolution or control. The composite endpoint occurred in 8.1% of the low MIC group and 9.1% of the high MIC group (P = 0.856). Median LOS was 4.9 days (IQR 3.7–8.0) in the low MIC group and 4.3 days (IQR 3.2–6.8) in the high MIC group (P = 0.384), and readmission rate was 17.2% in the low MIC group and 15.2% in the high MIC group (P = 0.787). Conclusion There was no between-group difference in the primary outcome of recurrence and mortality, with a low overall event rate and short LOS post-culture. These results suggest that levofloxacin effectiveness may be sustained in patients with MICs of 1 or 2 despite levofloxacin not meeting susceptibility criteria by new definitions. Disclosures All authors: No reported disclosures.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Johana Rondevaldova ◽  
Olga Leuner ◽  
Alemtshay Teka ◽  
Ermias Lulekal ◽  
Jaroslav Havlik ◽  
...  

Bacterial infections are in less-developed countries traditionally treated by remedies prepared from medicinal plants.Embelia schimperi(Vatke) is a plant used as a taenicide or disinfectant in Ethiopia, very often taken mixed with another plant species. In the present study, we examined two extracts prepared from seeds and twigs with leaves ofE. schimperiand its main present secondary metabolite embelin for their antibacterial combinatory effect with oxacillin and tetracycline against sensitive and resistantStaphylococcus aureusstrains. Minimum inhibitory concentrations were determined through the broth microdilution method, whereas the combinatory effect was evaluated through fractional inhibitory concentration sum (ΣFIC) indices. Results show many positive interactions and synergy occurring in embelin and oxacillin combinations against 4 out of 9 strains (ΣFIC 0.203–0.477) and for embelin and tetracycline combination against 3 out of 9 strains (ΣFIC 0.400–0.496). Moreover, the resistance to oxacillin has been overcome in 2 strains and to tetracycline in 3 strains. According to our knowledge, this is the first study showing antimicrobial combinatory effect ofE. schimperias well as of embelin. These findings can be used for the further research targeted on the development of new antistaphylococcal agents.


2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S313-S313
Author(s):  
S J Ryan Arends ◽  
Dee Shortridge ◽  
Mariana Castanheira ◽  
Jennifer M Streit ◽  
Robert K Flamm

Abstract Background Ceftolozane–tazobactam (C-T) is an antibacterial combination of a novel antipseudomonal cephalosporin and a β-lactamase inhibitor. C-T was approved by the US Food and Drug Administration in 2014 and by the European Medicines Agency in 2015 to treat complicated urinary tract infections, acute pyelonephritis, and complicated intra-abdominal infections. The Program to Assess Ceftolozane-Tazobactam Susceptibility (PACTS) monitors Gram-negative (GN) isolates resistant to C-T worldwide. In the current study, isolates were collected from patients hospitalized with bloodstream infections (BSIs) from 2015 to 2017 within the United States. Methods A total of 3,377 prevalence-based BSI GN isolates, including Escherichia coli (EC; 1,422), Klebsiella pneumoniae (KPN, 630), and Pseudomonas aeruginosa (PSA; 344), were collected during 2015 to 2017 from 32 PACTS hospitals in the United States. Isolates were tested for C-T susceptibility by CLSI broth microdilution method in a central monitoring laboratory (JMI Laboratories). Other antibiotics tested were amikacin (AMK), cefepime (FEP), ceftazidime (CAZ), colistin (COL), levofloxacin (LVX), meropenem (MEM), and piperacillin–tazobactam (TZP). Antibiotic-resistant phenotypes analyzed (CLSI, 2018) for EC and KPN included carbapenem-R (CR) and non-CR extended-spectrum β-lactamase (ESBL); as well as CAZ-nonsusceptible (CAZ-NS), MEM-NS, and COL-NS PSA. Results Of the 3,377 BSI GN isolates, 3,219 (95.3%) had a C-T MIC ≤ 4 mg/L. The three most prevalent GN species isolated from BSIs were EC (42.1%), KPN (18.7%), and PSA (10.2%). The %S of C-T and comparators for the top three pathogens are shown in the table. C-T showed activity against these isolates with %S of ≥96.0% against all three species. Of the comparators tested, AMK and COL also had high %S against these isolates. Conclusion C-T demonstrated activity against the most prevalent contemporary GN isolates from BSIs in the US. C-T was the only beta-lactam that had ≥96%S against all three species: EC, KPN, and PSA. For PSA, C-T maintained activity (>90%S) against isolates resistant to CAZ, TZP, and MEM. These data suggest that C-T may be a useful treatment for GN BSI. Disclosures S. J. R. Arends, Merck: Research Contractor, Research support. D. Shortridge, Merck: Research Contractor, Research support. M. Castanheira, Merck: Research Contractor, Research support. J. M. Streit, Merck: Research Contractor, Research support. R. K. Flamm, Merck: Research Contractor, Research support.


2020 ◽  
Vol 20 (10) ◽  
pp. 6063-6069
Author(s):  
Shenghua Cao ◽  
Xiaoqian Wu ◽  
Jianling Zhao ◽  
Xinhong Jia

To investigate the inhibitory effect of new nano silver (nAg-NPs) on Klebsiella pneumoniae producing extended spectrum β-lactamases (EBLs). Clinical interventions are mainly directed to inpatients, or patients with obvious discomfort, symptoms, and signs needing outpatient examination, referral, and clear diagnosis. We randomly selected 88 patients from the rehabilitation department of our hospital from November 2017 to June 2019, and divided them into observation and control groups by drawing lots. Taking ESBL K. pneumoniae as the research object, the bactericidal effect of nAg-NPs was determined using the coating method; the minimal inhibitory concentration (MIC) was measured using the broth microdilution method, and the mechanism of action of nAg-NPs on ESBL K. pneumoniae was evaluated by electron microscopy. After the implementation of different nursing management modes, the incidence of risk events in the observation group was significantly lower than that in the control group, and nursing satisfaction was significantly higher than that in the control group. nAg-NPs (≥0.5 g/mL) had 100% bactericidal effect on ESBL K. pneumoniae, 0.05 g/mL nAg-NPs had obvious bactericidal effect on ESBL K. pneumoniae, 5 g/mL nAg-NPs had obvious bactericidal effect on ESBL K. pneumoniae for 5, 15, 30 and 60 min. Additionally, nAg-NPs showed 3.12 g/mL of MIC. Furthermore, nAg-NPs had a significant effect on the morphology of K. pneumoniae. nAg-NPs shows obvious inhibitory effect on ESBL K. pneumoniae. These results will provide an experimental basis for the further study and clinical application of nAg-NPs with the help of clinical nurses.


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