scholarly journals A Real-World Study Comparing Various Antimicrobial Regimens for Bloodstream Infections Caused by Carbapenem-Resistant Gram-Negative Bacilli in a Tertiary Hospital, Shanghai, China, from 2010 to 2017

2020 ◽  
Vol Volume 13 ◽  
pp. 2453-2463
Author(s):  
Jiaying Tan ◽  
Wenjin Yu ◽  
Gang Wu ◽  
Jun Shen ◽  
Yong Fang ◽  
...  
Author(s):  
Agnieszka Chmielarczyk ◽  
Monika Pomorska-Wesołowska ◽  
Dorota Romaniszyn ◽  
Jadwiga Wójkowska-Mach

Introduction: Regardless of the country, advancements in medical care and infection prevention and control of bloodstream infections (BSIs) are an enormous burden of modern medicine. Objectives: The aim of our study was to describe the epidemiology and drug-resistance of laboratory-confirmed BSI (LC-BSIs) among adult patients of 16 hospitals in the south of Poland. Patients and methods: Data on 4218 LC-BSIs were collected between 2016–2019. The identification of the strains was performed using MALDI-TOF. Resistance mechanisms were investigated according to European Committee on Antimicrobial Susceptibility Testing, EUCAST recommendations. Results: Blood cultures were collected from 8899 patients, and LC-BSIs were confirmed in 47.4%. The prevalence of Gram-positive bacteria was 70.9%, Gram-negative 27.8% and yeast 1.4%. The most frequently isolated genus was Staphylococcus (50% of all LC-BSIs), with a domination of coagulase-negative staphylococci, while Escherichia coli (13.7%) was the most frequent Gram-negative bacterium. Over 4 years, 108 (2.6%) bacteria were isolated only once, including species from the human microbiota as well as environmental and zoonotic microorganisms. The highest methicillin resistant Staphylococcus aureus (MRSA) prevalence was in intensive care units (ICUs) (55.6%) but S. aureus with resistance to macrolides, lincosamides and streptogramins B (MLSB) in surgery was 66.7%. The highest prevalence of E. faecalis with a high-level aminoglycoside resistance (HLAR) mechanism was in ICUs, (84.6%), while E. faecium-HLAR in surgery was 83.3%. All cocci were fully glycopeptide-sensitive. Carbapenem-resistant Gram-negative bacilli were detected only in non-fermentative bacilli group, with prevalence 70% and more. Conclusions: The BSI microbiology in Polish hospitals was similar to those reported in other studies, but the prevalence of MRSA and enterococci-HLAR was higher than expected, as was the prevalence of carbapenem-resistant non-fermentative bacilli. Modern diagnostic techniques, such as MALDI-TOF, guarantee reliable diagnosis.


2017 ◽  
Vol 66 (2) ◽  
pp. 171-180 ◽  
Author(s):  
Fevronia Kolonitsiou ◽  
Matthaios Papadimitriou-Olivgeris ◽  
Anastasia Spiliopoulou ◽  
Vasiliki Stamouli ◽  
Vasileios Papakostas ◽  
...  

The aim of the study was to assess the epidemiology, the incidence of multidrug-resistant bacteria and bloodstream infections’ (BSIs) seasonality in a university hospital. This retrospective study was carried out in the University General Hospital of Patras, Greece, during 2011–13 y. Blood cultures from patients with clinical presentation suggestive of bloodstream infection were performed by the BacT/ALERT System. Isolates were identified by Vitek 2 Advanced Expert System. Antibiotic susceptibility testing was performed by the disk diffusion method and E-test. Resistance genes (mecA in staphylococci; vanA/vanB/vanC in enterococci; blaKPC/blaVIM/blaNDM in Klebsiella spp.) were detected by PCR. In total, 4607 (9.7%) blood cultures were positive from 47451 sets sent to Department of Microbiology, representing 1732 BSIs. Gram-negative bacteria (52.3%) were the most commonly isolated, followed by Gram-positive (39.5%), fungi (6.6%) and anaerobes bacteria (1.8%). The highest contamination rate was observed among Gram-positive bacteria (42.3%). Among 330 CNS and 150 Staphylococcus aureus, 281 (85.2%) and 60 (40.0%) were mecA-positive, respectively. From 113 enterococci, eight were vanA, two vanB and two vanC-positives. Of the total 207 carbapenem-resistant Klebsiella pneumoniae (73.4%), 202 carried blaKPC, four blaKPC and blaVIM and one blaVIM. A significant increase in monthly BSIs’ incidence was shown (R2: 0.449), which may be attributed to a rise of Gram-positive BSIs (R2: 0.337). Gram-positive BSIs were less frequent in spring (P < 0.001), summer (P < 0.001), and autumn (P < 0.001), as compared to winter months, while Gram-negative bacteria (P < 0.001) and fungi (P < 0.001) were more frequent in summer months. BSIs due to methicillin resistant S. aureus and carbapenem-resistant Gram-negative bacteria increased during the study period. The increasing incidence of BSIs can be attributed to an increase of Gram-positive BSI incidence, even though Gram-negative bacteria remained the predominant ones. Seasonality may play a role in the predominance of Gram-negative’s BSI.


2019 ◽  
Vol 6 (3) ◽  
pp. 180-185
Author(s):  
Zümrüt Şahbudak Bal ◽  
Muhterem Duyu ◽  
Fulya Kamit ◽  
Pınar Yazıcı ◽  
Ayşe Berna Anıl ◽  
...  

2019 ◽  
Vol 69 (Supplement_7) ◽  
pp. S544-S551 ◽  
Author(s):  
Yoshinori Yamano

AbstractCarbapenem-resistant gram-negative bacteria including Enterobacteriaceae as well as nonfermenters, such as Pseudomonas aeruginosa and Acinetobacter baumannii, have emerged as significant global clinical threats. Although new agents have recently been approved, none are active across the entire range of resistance mechanisms presented by carbapenem-resistant gram-negative bacteria. Cefiderocol, a novel siderophore cephalosporin, has been shown in large surveillance programs and independent in vitro studies to be highly active against all key gram-negative causative pathogens isolated from patients with hospital-acquired or ventilator-associated pneumonia, bloodstream infections, or complicated urinary tract infections. The improved structure, the novel mode of entry into bacteria, and its stability against carbapenemases enables cefiderocol to exhibit high potency against isolates that produce carbapenemases of all classes or are resistant due to porin channel mutations and/or efflux pump overexpression. Resistance to cefiderocol is uncommon and appears to be multifactorial.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S212-S212
Author(s):  
Yuko Matsunaga ◽  
Mari Ariyasu ◽  
Miki Takemura ◽  
Yoshinori Yamano ◽  
Kiichiro Toyoizumi ◽  
...  

Abstract Background The efficacy and safety of cefiderocol (CFDC), a novel siderophore cephalosporin, for the treatment of serious infections due to carbapenem-resistant (CR) Gram-negative pathogens was assessed in the CREDIBLE-CR study. The current analysis evaluated clinical and microbiological outcomes by baseline CR pathogen. Methods An open-label, prospective, randomised 2:1, Phase 3 study (CREDIBLE-CR; NCT02714595) was conducted in adult patients with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia, bloodstream infections or sepsis, and complicated urinary tract infections caused by CR Gram-negative pathogens. Patients received either intravenous (IV) CFDC 2g, q8h, 3-h infusion, or IV best available therapy (BAT: up to 3 drugs in combination), for 7–14 days (extendable to 21 days). Clinical and microbiological outcomes were assessed in the CR microbiological intent-to-treat (CR-MITT) population by CR pathogen, baseline MIC and by mechanism of carbapenem resistance at test of cure (TOC). Only summary statistics were collected. Results In the CR-MITT population (CFDC N=80; BAT N=38), Acinetobacter baumannii (46.3% and 44.7%), Klebsiella pneumoniae (33.8% and 31.5%), and Pseudomonas aeruginosa (15% and 26%) were the most frequent pathogens in CFDC and BAT arms, respectively. For all CR pathogens, clinical cure rates were achieved in 52.5% in the CFDC arm and 50.0% in the BAT arm at TOC; rates were similar between treatment arms by baseline CR pathogen (Table 1). Numerically higher clinical cure and microbiological outcomes were observed with CFDC for Enterobacterales (Table 1), especially against NDM-producing bacteria or those with porin-channel mutations (Table 1). CFDC MIC values ranged between ≤0.03 and 4 μg/mL, except for one pathogen (Table 2). Microbiological outcomes for CR A. baumannii, CR K. pneumoniae, and CR P. aeruginosa at TOC by baseline MICs of ≤4 μg/mL ranged between 0–40%, 0–100%, and 0–100%, respectively; at MIC ≤4 μg/mL, clinical and microbiological outcomes were equal (Table 2). Conclusion CFDC, via a novel mechanism of entry and its stability against β-lactamases, was effective against serious infections caused by CR pathogens with various resistance mechanisms or baseline MIC values. Disclosures Yuko Matsunaga, MD, Shionogi Inc. (Employee) Mari Ariyasu, BPharm, Shionogi & Co., Ltd. (Employee) Miki Takemura, MSc, Shionogi & Co., Ltd. (Employee) Yoshinori Yamano, PhD, Shionogi & Co., Ltd. (Employee) Kiichiro Toyoizumi, PhD, Shionogi & Co., Ltd. (Employee) Masahiro Kinoshita, MPharm, Shionogi & Co., Ltd. (Employee) Roger Echols, MD, Shionogi Inc. (Consultant) Tsutae Den Nagata, MD, Shionogi & Co., Ltd. (Employee)


Antibiotics ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 632 ◽  
Author(s):  
Matteo Bassetti ◽  
Antonio Vena ◽  
Chiara Sepulcri ◽  
Daniele Roberto Giacobbe ◽  
Maddalena Peghin

The rising incidence of bloodstream infections (BSI) due to Gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) has been recognized as a global emergency. The aim of this review is to provide a comprehensive assessment of the mechanisms of antibiotic resistance, epidemiology and treatment options for BSI caused by GNB with DTR, namely extended-spectrum Beta-lactamase-producing Enterobacteriales; carbapenem-resistant Enterobacteriales; DTR Pseudomonas aeruginosa; and DTR Acinetobacter baumannii.


2020 ◽  
Author(s):  
Xiaojuan Zhang ◽  
Shaoyan Qi ◽  
Xiaoguang Duan ◽  
Bing Han ◽  
Shuguang Zhang ◽  
...  

Abstract Background: High morbidity and mortality due to carbapenem-resistant Gram-negative bacilli (CRGNB) was a challenge for clinicians has led to the resurgence of polymyxin B (PMB) use in the last decade. The goal of our multicenter, real-world study was to evaluate the efficacy and safety of PMB in the treatment of CRGNB.Methods: The real-world study included the patients with intravenous PMB at least 7 days during the period of October 2018 to June 2019. Data was collected from electronic patients register and follow-up. The primary outcome was 28-day mortality, the secondary outcomes included hospital mortality, occurrence of adverse events during PMB therapy. Associations between these variables and 28-day mortality or all-cause hospital mortality were explored through univariate analyses and multivariable logistic regression. At the same time, therapeutic effects were observed. Results: The study included 100 patients. There were 39% presence of septic shock, 49% need mechanical ventilation at the beginning of therapy. The infection and condition improved after 7 days of PMB treatment. The major adverse reactions occurred in 16 cases (16%). The overall 28-day mortality was 40%. In terms of clinical characteristics, mean Sequential Organ Failure Assessment (6.77 versus 9.25,P = 0.004),mean Acute Physiology and Chronic Health Evaluation II (APACHEII) scores (16.17 versus 19.78, P = 0.016) and the number of patient with mechanical ventilation (21 versus 30, P = 0.000) or septic shock (17 versus 32, P = 0.000) were lower in survivors group than nonsurvivors group. The mortality of 85 patients with identify pathogens was 38.82%, while the mortality of patients with negative pathogen culture results was 46.67% (P = 0.580). Multivariate analysis showed that mechanical ventilation (P = 0.023, OR = 3.5; CI: 1.194–10.739), septic shock (P = 0.002, OR = 5.960; CI: 1.923–18.473) were associated with 28-day mortality.Conclusion: Our research found that PMB may be as effective and safe as standard antibiotics for the treatment of CRGNB. Timely and appropriate use of PMB will have a positive impact on the clinical outcomes of patients with sepsis in CRGNB.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S583-S583
Author(s):  
Mariana Castanheira ◽  
Michael D Huband ◽  
Robert K Flamm ◽  
Helio S Sader

Abstract Background Zidebactam (ZID) is a β-lactam enhancer antibiotic with a dual mechanism of action: high binding affinity to gram-negative PBP2 and β-lactamase (BL) inhibition. We evaluated the activity of cefepime (FEP) combined with ZID against contemporary clinical isolates of gram-negative bacilli (GNB) causing bloodstream infections (BSIs) in the US hospitals. Methods 1,239 GNB were consecutively collected (1/patient) from 34 US medical centers in 2018. Susceptibility (S) testing against FEP-ZID (1:1 ratio) and comparators were performed by reference broth microdilution method in a central laboratory. The FEP S breakpoint of ≤ 8 mg/L (CLSI, high dose) was applied to FEP-ZID for comparison purposes. An FEP-ZID S breakpoint of ≤ 64 mg/L has been proposed for non-fermentative GNB based on pharmacokinetic/pharmacodynamic target attainment and was also applied. Selected Enterobacterales (ENT) isolates were evaluated by whole-genome sequencing. Results FEP-ZID was highly active against ENT (MIC50/MIC90, 0.03/0.12 mg/L; highest MIC, 4 mg/L; Table), including multidrug-resistant (MDR, MIC50/MIC90, 0.12/0.25 mg/L) and carbapenem-resistant isolates (n = 7; MIC50, 0.5 mg/L). The highest FEP-ZID MIC values among E. coli, K. pneumoniae, and E. cloacae were 1, 2, and 0.25 mg/L, respectively. The most active comparators tested against MDR ENT were ceftazidime–avibactam (CAZ-AVI; MIC50/MIC90, 0.25/1 mg/L; 98.0%S), meropenem (MEM; MIC50/MIC90, 0.03/0.12 mg/L; 93.1%S) and amikacin (AMK; MIC50/MIC90, 4/16 mg/L; 92.1%S). The most active agents tested against P. aeruginosa were FEP-ZID (MIC50/MIC90, 1/4 mg/L; highest MIC, 8 mg/L), colistin (MIC50/MIC90, 0.5/1 mg/L; 100.0%S), and AMK (MIC50/MIC90, 4/8 mg/L; 99.2%S); whereas CAZ-AVI and ceftolozane–tazobactam were active against 96.5–96.7% of isolates. FEP-ZID exhibited good activity against Acinetobacter spp. (MIC50/MIC90, 2/8 mg/L) and S. maltophilia (MIC50/MIC90, 4/32 mg/L). S. maltophilia displayed low S rates to most comparators. Conclusion FEP-ZID demonstrated potent activity against a large collection GNB from BSI, including isolates resistant to other BL inhibitor combinations and/or carbapenems. These results support further clinical development of FEP-ZID. Disclosures All authors: No reported disclosures.


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