Carbapenem-resistant Pseudomonas aeruginosa pneumonia with intermediate minimum inhibitory concentrations to doripenem: combination therapy with high-dose, 4-h infusion of doripenem plus fosfomycin versus intravenous colistin plus fosfomycin

2012 ◽  
Vol 39 (3) ◽  
pp. 271-272 ◽  
Author(s):  
Anucha Apisarnthanarak ◽  
Linda M. Mundy
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Combination Therapy ◽  
High Dose ◽  
Minimum Inhibitory Concentrations ◽  
Carbapenem Resistant

scholarly journals Risk Factors and Mortality of Carbapenem-Resistant Klebsiella Pneumoniae Bloodstream Infection in a Tertiary-Care Hospital in China: An Eight-Year Retrospective Study

2020 ◽  
Author(s):  
Jie Chen ◽  
Hua Ma ◽  
Yongfeng Li ◽  
Michal Mastalerz ◽  
Ting Sheng ◽  
...  
Keyword(s):  
Risk Factors ◽  
Septic Shock ◽  
Severe Sepsis ◽  
Retrospective Study ◽  
Combination Therapy ◽  
Antimicrobial Therapy ◽  
Hematologic Malignancies ◽  
Mortality Rates ◽  
High Dose ◽  
Carbapenem Resistant

Abstract Background: The prevalence of carbapenem-resistant Klebsiella pneumonia bloodstream infection (CRKP-BSI) is increasing worldwide. CRKP-BSI is associated with high rates of morbidity and mortality due to limited antibiotic choices. Here, we aim to identify the prevalence and risk factors for infection and mortality of CRKP BSI. Methods: This was a retrospective study of the past data from January 1st, 2012 to December 31st, 2019 of adult patients with KP-BSI in Xiangya Hospital, China. Data from Demographic and clinical findings were retrieved from medical records. Results: Among the 706 incidences included in this study, 27.4% of them (212 / 753) being CR-KP strains. The occurrence of CRKP-BSI was increased from 20.69 to 37.40% from 2012 to 2019. Hematologic malignancies (P<0.001 , odds ratio [OR] 4.68, 95% confidence interval [CI] 2.3–9.4) and ICU acquired infection (P=0.003 , OR 2.10, 95% CI 1.3–3.4) were identified to be substantial risk factors of carbapenem resistance. The overall 28-day mortality rates of CRKP-BSI patients was significantly higher than that of CSKP-BSI (P<0.001). Logistic regression analysis identified severe sepsis or septic shock incidents (OR, 8.44; 95% CI, 1.85–38.39), inadequate empirical antimicrobial therapy (OR, 15.01; 95% CI, 3.70–60.79) and corticosteroids use preceding infection onset (OR, 6.45; 95% CI, 1.12–37.08) as the independent predictors of 28-day mortality of CRKP-BSI patients. However, high dose carbapenem combination therapy was identified as anticipated factors of low 28-day mortality (OR, 0.11; 95% CI, 0.03–0.51).Conclusion: The occurrence of CRKP-BSI was significantly increased during the study period. Hematologic malignancies and ICU acquired infection were associated with the development of CRKP BSI. Severe sepsis or septic shock incidents, inadequate empirical antimicrobial therapy and corticosteroids use preceding infection onset caused significant increase of mortality rates in CRKP-BSI patients. High dose carbapenem combination therapy was associated with better outcome.

scholarly journals Antibacterial Activity of Human Simulated Epithelial Lining Fluid Concentrations of Ceftazidime-Avibactam Alone or in Combination with Amikacin Inhale (BAY41-6551) against Carbapenem-Resistant Pseudomonas aeruginosa and Klebsiella pneumoniae

2018 ◽  
Vol 62 (7) ◽  
Author(s):  
Safa S. Almarzoky Abuhussain ◽  
Joseph L. Kuti ◽  
David P. Nicolau
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Combination Therapy ◽  
Klebsiella Pneumoniae ◽  
Combination Regimen ◽  
Epithelial Lining ◽  
Beta Lactam ◽  
Chemostat Model ◽  
Epithelial Lining Fluid ◽  
Content Type ◽  
Carbapenem Resistant

ABSTRACT The role of inhalational combination therapy when treating carbapenem-resistant Pseudomonas aeruginosa and Klebsiella pneumoniae with newer beta-lactam/beta-lactamase inhibitors has not been established. Using a 72-h in vitro pharmacodynamic chemostat model, we simulated the human exposures achieved in epithelial lining fluid (ELF) following intravenous treatment with ceftazidime-avibactam (CZA) 2.5 g every 8 h (q8h) alone and in combination with inhaled amikacin (AMK-I) 400 mg q12h, a reformulated aminoglycoside designed for inhalational administration, against three P. aeruginosa isolates (CZA [ceftazidime/avibactam] MICs, 4/4 to 8/4 μg/ml; AMK-I MICs, 8 to 64 μg/ml) and three K. pneumoniae isolates (CZA MICs, 1/4 to 8/4 μg/ml; AMK-I MICs, 32 to 64 μg/ml). Combination therapy resulted in a significant reduction in 72-h CFU compared with that of CZA monotherapy against two of three P. aeruginosa isolates (−4.14 log 10 CFU/ml, P = 0.027; −1.42 log 10 CFU/ml, P = 0.020; and −0.4 log 10 CFU/ml, P = 0.298) and two of three K. pneumoniae isolates (0.04 log 10 CFU/ml, P = 0.963; −4.34 log 10 CFU/ml, P < 0.001; and −2.34 log 10 CFU/ml, P = 0.021). When measured by the area under the bacterial growth curve (AUBC) over 72 h, significant reductions were observed in favor of the combination regimen against all six isolates tested. AMK-I combination therapy successfully suppressed CZA resistance development in one K. pneumoniae isolate harboring bla KPC-3 that was observed during CZA monotherapy. These studies suggest a beneficial role for combination therapy with intravenous CZA and inhaled AMK when treating pneumonia caused by carbapenem-resistant Gram-negative bacteria.

scholarly journals Effect of combination therapy containing a high-dose carbapenem on mortality in patients with carbapenem-resistant Klebsiella pneumoniae bloodstream infection

2018 ◽  
Vol 51 (2) ◽  
pp. 244-248 ◽  
Author(s):  
Maddalena Giannella ◽  
Enrico Maria Trecarichi ◽  
Daniele Roberto Giacobbe ◽  
Francesco Giuseppe De Rosa ◽  
Matteo Bassetti ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Klebsiella Pneumoniae ◽  
Bloodstream Infection ◽  
High Dose ◽  
Carbapenem Resistant

scholarly journals 1256. Clinical Response by Minimum Inhibitory Concentrations in Carbapenem-Resistant Pseudomonas aeruginosa Infections under Cefiderocol Compassionate Use Program

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S717-S717
Author(s):  
Michael J Satlin ◽  
David Fam ◽  
Roger Echols ◽  
Christopher Longshaw ◽  
Miki Takemura ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Clinical Response ◽  
Treatment Options ◽  
Clinical Response Rate ◽  
Compassionate Use ◽  
Minimum Inhibitory Concentrations ◽  
Carbapenem Resistant ◽  
Clinical Responses ◽  
The Impact ◽  
Research Grant

Abstract Background Cefiderocol (CFDC) has been developed for the treatment of serious infections caused by drug-resistant aerobic Gram-negative pathogens, including carbapenem-resistant (CR) Pseudomonas aeruginosa (CRPA). The current CFDC susceptibility breakpoints for P. aeruginosa differ between US Food and Drug Administration (FDA) and Clinical and Laboratory Standards Institute (CLSI) (Table). Data characterizing the impact of CFDC minimum inhibitory concentrations (MICs) on the clinical responses of patients treated with CFDC for CRPA are sparse. Methods We reviewed patients treated with compassionate-use CFDC (2 g, q8h or renally adjusted dosages) for infections caused by CRPA with no alternative treatment options. CFDC minimum inhibitory concentrations (MICs) were evaluated according to CLSI guidelines in iron-depleted cation-adjusted Müller–Hinton broth for available CRPA isolates. We then assessed physician-reported clinical responses to CFDC therapy and stratified results by CFDC MIC. Results There were 71 patients overall with CRPA treated with CFDC. Treatment duration ranged from 1 to 132 days. For the subset of 33 patients for whom CFDC MIC values were available, the most common infection sites were the respiratory tract (n=15), blood (n=12), and urinary tract (n=4). Patients could have had an infection at ≥1 sites and in other locations. CFDC MIC range was ≤0.03– &gt;64 µg/mL. The modal MIC value was 2 µg/mL (n=13; Table). CRPA isolates were susceptible to CFDC in 13/33 patients (39.4%) based on the FDA breakpoint (MIC ≤1 µg/mL) and in 31/33 patients (93.9%) based on the CLSI breakpoint (MIC ≤4 µg/mL). Clinical response was reported for 15/18 patients (83.3%) who had infections with CFDC MICs of 2–4 µg/mL, organisms that are considered susceptible by CLSI but not by FDA breakpoints (Table). Clinical response was reported in 6/13 patients (46.1%) with infections with CFDC MIC ≤1 µg/mL and in 1 of 2 patients (50.0%) with CFDC MIC ≥8 µg/mL (Table). 21 (63.6%) patients survived to Day 28 and there were no trends in mortality by CFDC MIC. Conclusion Clinical response rate was high for CRPA infections with CFDC MICs of 2–4 µg/mL, supporting the higher CLSI susceptibility breakpoint. Disclosures Michael J. Satlin, MD, MS, Achaogen (Consultant)Allergan (Research Grant or Support)BioFire Diagnostics (Research Grant or Support)Merck (Research Grant or Support)Shionogi (Consultant) David Fam, PharmD, Shionogi (Employee) Roger Echols, MD, Shionogi (Consultant) Christopher Longshaw, PhD, Shionogi (Employee) Miki Takemura, MS, SHIONOGI & CO., LTD. (Employee) Yoshinori Yamano, PhD, Shionogi (Employee)

scholarly journals 1266. Characterization of Shifts in Minimum Inhibitory Concentrations During Treatment with Cefiderocol or Comparators in the Phase 3 CREDIBLE-CR and APEKS-NP Studies

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S649-S650
Author(s):  
Miki Takemura ◽  
Yoshinori Yamano ◽  
Yuko Matsunaga ◽  
Mari Ariyasu ◽  
Roger Echols ◽  
...  
Keyword(s):  
Target Gene ◽  
Study Drug ◽  
High Dose ◽  
Phase 3 ◽  
Minimum Inhibitory Concentrations ◽  
Carbapenem Resistant ◽  
Serious Infections ◽  
Enzyme Mutation ◽  
Extended Infusion

Abstract Background Cefiderocol (CFDC) is a novel siderophore cephalosporin developed to treat serious carbapenem-resistant (CR) Gram-negative (GN) infections. Methods In CREDIBLE-CR (NCT02714595), adults with serious infections caused by CR GN pathogens received CFDC 2 g, q8h, 3-h infusion, or best available therapy (BAT). In APEKS-NP (NCT03032380), adults with nosocomial pneumonia received CFDC or high-dose, extended-infusion meropenem (each 2 g, q8h, 3-h infusion). All treatments were given for 7‒14 days (extendable to 21 days). Biospecimens were collected before the first dose of study drug and at subsequent visits for assessments, and minimum inhibitory concentrations (MIC) to various antibiotics, including CFDC and carbapenems, were determined. Isolates with an increased MIC were evaluated by RT-PCR or whole genome sequencing (WGS) for CFDC resistance-related genes or mutations. Results for genetically related isolates with an elevated MIC during therapy are shown. Results On-therapy ≥4-fold CFDC MIC increase was found in 12 out of 106 (CREDIBLE-CR; Table 1) and 7 out of 159 (APEKS-NP; Table 2) isolates, respectively. For most isolates, CFDC MIC increased by 4–8-fold but remained ≤4 µg/mL. Specific mutations which could explain CFDC MIC increases were found in only 3 isolates. Mutations in iron-transport related genes were not identified. Mutation in CFDC target gene PBP-3 was identified in 1 A. baumannii isolate. Class-C enzyme mutation was observed in 2 isolates (CREDIBLE-CR: PDC-30 in P. aeruginosa; APEKS-NP: ACT-17 in E. cloacae), although the contribution to CFDC MIC increase has not been confirmed. In the BAT arm in CREDIBLE-CR, 6 out of 46 isolates had ≥4-fold MIC increase; all post-treatment isolates were resistant to BAT agents (Table 1), although WGS was not conducted for these isolates. In the meropenem arm in APEKS-NP, 5 out of 164 isolates had ≥4-fold MIC increase (Table 2). Table 1. MIC changes in CREDIBLE-CR Table 2. MIC changes in APEKS-NP Conclusion Among isolates with ≥4-fold MIC increase during CFDC treatment, actual CFDC MIC values remained relatively low for most isolates. Frequency of MIC increase in BAT or meropenem arms was similar to that of CFDC, but the magnitude was greater. Acquisition of contributory mechanism has not been identified except for the mutation in PBP 3 and some β-lactamases. Disclosures Miki Takemura, MSc, Shionogi & Co., Ltd. (Employee) Yoshinori Yamano, PhD, Shionogi & Co., Ltd. (Employee) Yuko Matsunaga, MD, Shionogi Inc. (Employee) Mari Ariyasu, BPharm, Shionogi & Co., Ltd. (Employee) Roger Echols, MD, Shionogi Inc. (Consultant) Tsutae Den Nagata, MD, Shionogi & Co., Ltd. (Employee)

scholarly journals Carbapenem-resistant Pseudomonas aeruginosa bloodstream infection: in vitro synergy, virulence and clinical outcome

2018 ◽  
Author(s):  
Jessica Fernandes Ramos ◽  
Gleice Cristina Leite ◽  
Camila Rizek ◽  
Flavia Rossi ◽  
Thais Guimarães ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Combination Therapy ◽  
Clinical Outcome ◽  
Bloodstream Infection ◽  
The Other ◽  
Lower Mortality ◽  
Carbapenem Resistant ◽  
Other Hand

AbstractIn the current study carbapanem-resistant P. aeruginosa bloodstream infection (CRPA-BSI) was associated with high 14-day mortality. Although, highly resistant to meropenem, half of the isolates achieved in vitro synergy with the combination of meropenem with colistin, and the patients that received this combination therapy showed a tendency towards lower mortality. Our strains did not carry exoU gene, on the other hand, patients with CRPA-BSI caused by strains harboring gene lasB evolved more frequent to death.

Sign in / Sign up

Export Citation Format

Share Document