Monotherapy with High-Dose Once-Daily Tigecycline is Highly Effective Against Acinetobacter baumanii and other Multidrug-Resistant (MDR) Gram-Negative Bacilli (GNB)

2018 ◽  
Vol 52 (1) ◽  
pp. 119-120 ◽  
Author(s):  
Burke A. Cunha ◽  
Jeffrey Baron ◽  
Cheston B. Cunha
Keyword(s):  
Multidrug Resistant ◽  
High Dose ◽  
Acinetobacter Baumanii ◽  
Once Daily ◽  
Gram Negative ◽  
Highly Effective

Efficacy and Safety of a Colistin Loading Dose, High-Dose Maintenance Regimen in Critically Ill Patients With Multidrug-Resistant Gram-Negative Pneumonia

2016 ◽  
Vol 32 (8) ◽  
pp. 487-493 ◽  
Author(s):  
Jessica L. Elefritz ◽  
Karri A. Bauer ◽  
Christian Jones ◽  
Julie E. Mangino ◽  
Kyle Porter ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Clinical Cure ◽  
Statistical Significance ◽  
Cohort Analysis ◽  
Kidney Injury ◽  
Multidrug Resistant ◽  
High Dose ◽  
Loading Dose ◽  
Gram Negative

Introduction: Emergence of multidrug-resistant (MDR) gram-negative (GN) pathogens and lack of novel antibiotics have increased the use of colistin, despite unknown optimal dosing. This study aimed to evaluate the safety and efficacy of a colistin loading dose, high-dose (LDHD) maintenance regimen in patients with MDR-GN pneumonia. Methods: A retrospective cohort analysis was performed comparing critically ill patients with MDR-GN pneumonia pre- and postimplementation of a colistin LDHD guideline with a primary outcome of clinical cure. Safety was assessed using incidence of acute kidney injury (AKI) based on RIFLE (risk, injury, failure, loss, end-stage renal disease) criteria. Results: Seventy-two patients met the inclusion criteria (42 preimplementation and 30 postimplementation). Clinical cure was achieved in 23 (55%) patients in the preimplementation group and 20 (67%) patients in the postimplementation group ( P = .31). AKI occurred in 50% of the patients during the preimplementation period and 58% during the postimplementation period ( P = .59) with no difference in initiation rates of renal replacement therapy. Conclusion: The increased clinical cure rate after implementation of the colistin LDHD guideline did not reach statistical significance. The LDHD guideline, however, was not associated with an increased incidence of AKI, despite higher intravenous colistin doses. Opportunity exists to optimize colistin dosage while balancing toxicity, but larger studies are warranted.

scholarly journals 1598. Antimicrobial Activity of the Novel β-Lactam Enhancer Combination Cefepime–Zidebactam (WCK-5222) Tested Against Gram-Negative Bacteria Isolated in United States Medical Centers from Patients with Bloodstream Infections

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S583-S583
Author(s):  
Mariana Castanheira ◽  
Michael D Huband ◽  
Robert K Flamm ◽  
Helio S Sader
Keyword(s):  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
High Dose ◽  
Gram Negative ◽  
Highly Active ◽  
Microdilution Method ◽  
Medical Centers ◽  
Carbapenem Resistant ◽  
Broth Microdilution Method ◽  
Dual Mechanism

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.

scholarly journals 2192. Comparative Antimicrobial Susceptibility of Gram-Negative Bacteria Isolated from Patients with Bloodstream Infections and Pneumonia when Tested against Tazobactam Combinations

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S746-S746
Author(s):  
Cecilia G Carvalhaes ◽  
Rodrigo E Mendes ◽  
Robert K Flamm ◽  
Helio S Sader
Keyword(s):  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
Clinical Development ◽  
High Dose ◽  
Gram Negative ◽  
Medical Centers ◽  
Carbapenem Resistant ◽  
Study Support ◽  
Acinetobacter Spp ◽  
Extended Infusion

Abstract Background Cefepime–tazobactam (FEP-TAZ) is in clinical development at 2g/2g q8 hours administered over 90 minutes (high-dose extended infusion). We compared the susceptibility (S) of Gram-negative bacilli (GNB) from patients with bloodstream infections (BSI) and pneumonia (PN) against FEP-TAZ, piperacillin–tazobactam (PIP-TAZ), and ceftolozane–tazobactam (C-T). Methods In 2018, 3,389 GNB isolates (1/patient) were consecutively collected from patients with BSIs (1,349) and PN (2,040) in 40 United States (US) medical centers, and tested by reference broth microdilution methods for S against FEP-TAZ (TAZ at fixed 8 mg/L), PIP-TAZ, C-T, and comparators. The percentage of isolates inhibited at ≤8 mg/L (CLSI, cefepime high dose) and at ≤ 16 mg/L (pharmacokinetic/pharmacodynamic [PK/PD] S breakpoint based on extended infusion and high dosage) of FEP-TAZ were evaluated. Results FEP-TAZ (MIC50/90, 0.06/0.25 mg/L) was the most active TAZ combination against Enterobacterales (ENT) with a spectrum similar to that of meropenem (MEM; 99.3/97.2%S for BSI/PN), ceftazidime–avibactam (CAZ-AVI; 99.8/99.9%S), and amikacin (AMK; 99.3/98.3%S) and retained good activity against ceftriaxone-non-S (CRO-NS) and multidrug-resistant (MDR) ENT (table). Among the β-lactams (BLMs) tested, only FEP-TAZ (57.1/58.6% [BSI/PN] inhibited at ≤ 16 mg/L) and CAZ-AVI (71.4/96.6%S) were active against carbapenem-resistant ENT (CRE). CAZ-AVI (96.7/95.2%S for BSI/PN) and C-T (96.5/94.5%S) were the most active BLMs tested against P. aeruginosa (PSA), followed by FEP-TAZ (95.0/92.1% inhibited a ≤ 16 mg/L), FEP (89.3/78.2%S), and CAZ (85.1/79.0%S). FEP-TAZ (77.8/77.3% inhibited at ≤ 16 mg/L), C-T (81.2/82.9%S), and CAZ-AVI (77.8/84.5%S) retained activity against MEM-NS PSA. FEP-TAZ was the most active BLM against Acinetobacter spp. when the proposed PK/PD breakpoint was applied. Conclusion S rates were markedly lower among isolates from PN compared with BSI. FEP-TAZ was the most active TAZ combination tested against GNB isolated from patients with BSI and PN from US hospitals and exhibited greater spectrum than the carbapenems. The results of this study support further clinical development of high-dose extended-infusion FEP-TAZ for treatment of GNB infections. Disclosures All authors: No reported disclosures.

scholarly journals 388. Multidrug Resistant Gram Negative Organisms Prevalence in Hospitalized Patients in an Italian Tertiary Level Hospital During COVID-19 Pandemia: First Detection is More Frequent in Clinical Samples than in Surveillance Rectal Swabs with Respect to the Previous 14-Month Period

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S262-S263
Author(s):  
Monica Basso ◽  
Daniela Zago ◽  
Ettore De Canale ◽  
Maria Angela Biasolo ◽  
Elisa Franchin ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Infection Control ◽  
Multidrug Resistant ◽  
Control Measures ◽  
Clinical Samples ◽  
Published Data ◽  
Acinetobacter Baumanii ◽  
Gram Negative ◽  
Surgical Department ◽  
Rectal Swabs

Abstract Background In Italy the pandemic of COVID-19 infection has placed an enormous burden on health authorities: contact precautions are required to avoid viral transmission and people should be subjected to standard infection control procedures. This is crucial in a country experiencing a high number of confirmed cases of COVID-19 infection in Europe and where multidrug-resistant Gram-negative bacteria (MDR-GN) are endemic.The aim of this study was to compare the prevalence of MDR-GN in surveillance rectal swabs (SRS) and in clinical samples (CS) in the period March 1,2020-April, 24 2020 with respect to the previous 2-month period and to the previous year. Methods The first SRS and the first CS with a MDR-GN isolate detected from 01/01/2019 to 24/04/2020 were included. Analysis was made by comparing three different study periods in 2019 and 2020 (Jan-Dec 2019, Jan-Feb 2020, and Mar-Apr 2020), for medical department, surgical department and intensive care department. Results Overall, 612 MDR-GN organisms were identified (399 SRS and 213 CS): carbapenemase-producing Klebsiella pneumoniae and Acinetobacter baumanii (CPAB) were the most frequently detected (Figure 1). We observed an increased relative frequency of patients with MDR-GN detected in CS respect to those found in SRS (32.7% vs 44.5% vs 70.6%, p=0.0005): 5/12 CS detected in the last period were isolated from the respiratory tract (Figure 2). Nine patients with COVID-19 pneumonia had MDR-GN. All but two patients had a previous negative SRS performed 4 days before (median value) and the median interval between COVID-19 positivity and MDR-GN positivity was 7 days.The six patients with CPAB isolation were all hospitalized in the same ward, with partially overlapping hospital stays during the study period. In 5 of them, CPAB was detected in the respiratory tract (Figure 3). Conclusion The first detection of MDR-GN in CS and the nosocomial MDR-GN acquisition despite cohorting due to COVID-19 infection underline the need to reinforce infection control measures in a high prevalence country during COVID-19 pandemia. A correct antimicrobial policy urged because, according to published data, most patients with COVID-19 infection received antimicrobial therapy: furthermore MDR-GN infection could play a role in the negative outcome of these patients. Disclosures All Authors: No reported disclosures

HERE, THERE AND EVERYWHERE: A HOSPITAL-BASED STUDY ON NOSOCOMIALAND ENVIRONMENTAL NON-FERMENTERS

2021 ◽  
pp. 71-73
Author(s):  
Malabika Biswas ◽  
Bishal Gupta ◽  
Anindita Rakshit ◽  
Netai Pramanik ◽  
Banya Chakraborty ◽  
...  
Keyword(s):  
Antibiotic Susceptibility ◽  
Environmental Contaminants ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Hospital Environment ◽  
Acinetobacter Baumanii ◽  
Gram Negative ◽  
Cross Transmission ◽  
Hospital Acquired ◽  
Automated Methods

Aim: To assess the prevalence of non-fermenting gram negative bacilli(NFGNB) as nosocomial pathogens and environmental contaminants. Material and Methods: Nonfermenting gram negative bacilli were isolated from relevant patient samples and high-touch surfaces in the hospital environment. They were identied and their antibiotic susceptibility testing was done using conventional and automated methods. Result: The prevalence of nonfermenters as hospital acquired pathogens and as environmental contaminants was 25.8% and 16.3% respectively. All clinical isolates of Acinetobacter baumanii cplx and Pseudomonas aeruginosa were multidrug resistant. Cluster analysis of clinical isolates show similar antibiotic susceptibility prole indicating an ongoing cross-transmission in the hospital.

scholarly journals The GspLM inner membrane complex from the bacterial type II secretion system is a dimer of dimers and interacts with the system ATPase with high affinity

2020 ◽  
Author(s):  
Aleksandra Fulara ◽  
Ioanna Ramou ◽  
Savvas N. Savvides
Keyword(s):  
Multidrug Resistant ◽  
Secretion System ◽  
Klebsiella Pneumonia ◽  
Type Ii Secretion ◽  
Type Ii ◽  
Acinetobacter Baumanii ◽  
Inner Membrane ◽  
Gram Negative ◽  
High Affinity ◽  
Type Ii Secretion System

ABSTACTThe type II secretion system (T2SS) is a multiprotein machinery spanning the diderm of gram-negative bacteria. T2SS contributes to the virulence of numerous gram-negative pathogens, including the multidrug resistant species Pseudomonas aeruginosa, Acinetobacter baumanii, Klebsiella pneumonia and Vibrio cholerae. Even though the T2SS has been studied extensively over the past three decades, our understanding of the molecular basis of its biogenesis and of its overall structure still remains unclear. Here we show that the core component of the inner membrane platform, the GspLM membrane protein complex, can be isolated as a dimer of dimers. Importantly, the complex is able to bind the T2SS ATPase, GspE, with high affinity. Finally, we have developed single domain VHH camelid antibodies (nanobodies) against the GspLM complex and have identified a nanobody that effectively prevents the cytoplasmic domain of GspL, GspLcyto, from binding to GspE. Our findings suggest that the T2SS ATPase is permanently associated with the inner membrane platform and that the GspELM complex should be considered as a key subassembly for the biogenesis of the T2SS apparatus.

Successful use of once‐daily high‐dose darunavir and dolutegravir in multidrug‐resistant HIV

2019 ◽  
Vol 45 (2) ◽  
pp. 394-396 ◽  
Author(s):  
Patricia P. Fulco ◽  
Crystal R. Leibrand Kaczmar ◽  
Denese Gomes ◽  
Tima Smith
Keyword(s):  
Multidrug Resistant ◽  
High Dose ◽  
Once Daily

scholarly journals Ceftolozane–tazobactam for the treatment of osteomyelitis caused by multidrug-resistant pathogens: a case series

2019 ◽  
Vol 11 ◽  
pp. 204209861986208 ◽  
Author(s):  
Xing Tan ◽  
Ryan P. Moenster
Keyword(s):  
Case Reports ◽  
Case Series ◽  
Complicated Urinary Tract Infection ◽  
Multidrug Resistant ◽  
High Dose ◽  
Gram Negative ◽  
The Us ◽  
Attractive Option ◽  
Gram Negative Organisms

Ceftolozane–tazobactam (CT) is a recently approved novel cephalosporin and β-lactamase inhibitor combination agent with in vitro activity against various Gram-positive and Gram-negative pathogens, including several multidrug-resistant (MDR) Gram-negative organisms. CT is currently approved by the US Food and Drug Administration for the treatment of complicated intrabdominal infection and complicated urinary tract infection at a dose of 1.5 g intravenously every 8 h. This agent is an attractive option for MDR osteomyelitis (OM) treatment, but clinical data is limited to case reports and series. Here we report a series of five patients with MDR OM who were treated with CT. Pathogens involved in these infections were MDR Acinetobacter baumannii (two isolates) and MDR Pseudomonas aeruginosa (four isolates). Two patients were disease free 6 months after therapy was discontinued, one required an additional curative surgical procedure, and two (both on high-dose therapy) developed adverse reactions likely related to CT that necessitated early antibiotic discontinuation.

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