scholarly journals Infectious Diseases Society of America Guidance on the Treatment of AmpC β-lactamase-Producing Enterobacterales, Carbapenem-Resistant Acinetobacter baumannii, and Stenotrophomonas maltophilia Infections

2021 ◽  
Author(s):  
Pranita D Tamma ◽  
Samuel L Aitken ◽  
Robert A Bonomo ◽  
Amy J Mathers ◽  
David van Duin ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Acinetobacter Baumannii ◽  
Stenotrophomonas Maltophilia ◽  
The United States ◽  
Causative Organism ◽  
Published Data ◽  
Guidance Document ◽  
Duration Of Therapy ◽  
Carbapenem Resistant ◽  
Pediatric Populations

Abstract Background The Infectious Diseases Society of America (IDSA) is committed to providing up-to-date guidance on the treatment of antimicrobial-resistant infections. A previous guidance document focused on infections caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa). Here, guidance is provided for treating AmpC β-lactamase-producing Enterobacterales (AmpC-E), carbapenem-resistant Acinetobacter baumannii (CRAB), and Stenotrophomonas maltophilia infections. Methods A panel of six infectious diseases specialists with expertise in managing antimicrobial-resistant infections formulated questions about the treatment of AmpC-E, CRAB, and S. maltophilia infections. Answers are presented as suggestions and corresponding rationales. In contrast to guidance in the previous document, published data on optimal treatment of AmpC-E, CRAB, and S. maltophilia infections are limited. As such, guidance in this document is provided as “suggested approaches” based on clinical experience, expert opinion, and a review of the available literature. Because of differences in the epidemiology of resistance and availability of specific anti-infectives internationally, this document focuses on the treatment of infections in the United States. Results Preferred and alternative treatment suggestions are provided, assuming the causative organism has been identified and antibiotic susceptibility results are known. Approaches to empiric treatment, duration of therapy, and other management considerations are also discussed briefly. Suggestions apply for both adult and pediatric populations. Conclusions The field of antimicrobial resistance is highly dynamic. Consultation with an infectious diseases specialist is recommended for the treatment of antimicrobial-resistant infections. This document is current as of September 17, 2021 and will be updated annually. The most current versions of IDSA documents, including dates of publication, are available at www.idsociety.org/practice-guideline/amr-guidance-2.0/.

scholarly journals Infectious Diseases Society of America Guidance on the Treatment of Extended-Spectrum β-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa)

2020 ◽  
Author(s):  
Pranita D Tamma ◽  
Samuel L Aitken ◽  
Robert A Bonomo ◽  
Amy J Mathers ◽  
David van Duin ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Infectious Diseases ◽  
The United States ◽  
Treatment Recommendations ◽  
Causative Organism ◽  
Guidance Document ◽  
Current Version ◽  
Carbapenem Resistant ◽  
Extended Spectrum ◽  
Adults And Children

Abstract Background Antimicrobial-resistant infections are commonly encountered in US hospitals and result in significant morbidity and mortality. This guidance document provides recommendations for the treatment of infections caused by extended-spectrum β-lactamase–producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa). Methods A panel of 6 infectious diseases specialists with expertise in managing antimicrobial-resistant infections formulated common questions regarding the treatment of ESBL-E, CRE, and DTR-P. aeruginosa infections. Based on review of the published literature and clinical experience, the panel provide recommendations and associated rationale for each recommendation. Because of significant differences in the molecular epidemiology of resistance and the availability of specific anti-infective agents globally, this document focuses on treatment of antimicrobial-resistant infections in the United States. Results Approaches to empiric treatment selection, duration of therapy, and other management considerations are briefly discussed. The majority of guidance focuses on preferred and alternative treatment recommendations for antimicrobial-resistant infections, assuming that the causative organism has been identified and antibiotic susceptibility testing results are known. Treatment recommendations apply to both adults and children. Conclusions The field of antimicrobial resistance is dynamic and rapidly evolving, and the treatment of antimicrobial-resistant infections will continue to challenge clinicians. This guidance document is current as of 17 September 2020. Updates to this guidance document will occur periodically as new data emerge. Furthermore, the panel will expand recommendations to include other problematic gram-negative pathogens in future versions. The most current version of the guidance including the date of publication can be found at www.idsociety.org/practice-guideline/amr-guidance/.

scholarly journals Multicity Outbreak of Carbapenem-Resistant Acinetobacter baumannii Isolates Producing the Carbapenemase OXA-40

2006 ◽  
Vol 50 (9) ◽  
pp. 2941-2945 ◽  
Author(s):  
Karen Lolans ◽  
Thomas W. Rice ◽  
L. Silvia Munoz-Price ◽  
John P. Quinn
Keyword(s):  
Acinetobacter Baumannii ◽  
Carbapenem Resistance ◽  
The United States ◽  
Nucleotide Sequencing ◽  
Sequencing Analysis ◽  
Carbapenem Resistant ◽  
Extended Care ◽  
Care Facilities ◽  
High Level ◽  
First Time

ABSTRACT During 2005 we detected a multicity outbreak of infections or colonization due to high-level imipenem-resistant Acinetobacter baumannii (MIC, 64 μg/ml). One hundred isolates from diverse sources were obtained from seven acute-care hospitals and two extended-care facilities; 97% of the isolates belonged to one clone. Susceptibility testing of the first 42 isolates (January to April 2005) revealed broad resistance profiles. Half of the isolates were susceptible to ceftazidime, with many isolates susceptible only to colistin. The level of AmpC β-lactamase expression was stronger in isolates resistant to ceftazidime. PCR and subsequent nucleotide sequencing analysis identified bla OXA-40. The presence of an OXA-40 β-lactamase in these isolates correlated with the carbapenem resistance. By Southern blot analysis, a bla OXA-40-specific probe revealed that the gene was both plasmid and chromosomally located. This is the first time in the United States that such carbapenem resistance in A. baumannii has been attributable to a carbapenemase.

scholarly journals Antibiotic Susceptibility, Clonality, and Molecular Characterization of Carbapenem-Resistant Clinical Isolates of Acinetobacter baumannii from Washington DC

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Garima Bansal ◽  
Rachelle Allen-McFarlane ◽  
Broderick Eribo
Keyword(s):  
Acinetobacter Baumannii ◽  
Multiplex Pcr ◽  
Antibiotic Susceptibility ◽  
Carbapenem Resistance ◽  
The United States ◽  
Pcr Analysis ◽  
Washington Dc ◽  
Antibiotic Resistant ◽  
Group 4 ◽  
Carbapenem Resistant

The occurrence of carbapenem-resistant (CR) strains of Acinetobacter baumannii is reported to contribute to the severity of several nosocomial infections, especially in critically ill patients in intensive care units. The present study aims to determine the antibiotic susceptibility, clonality, and genetic mechanism of carbapenem resistance in twenty-eight Acinetobacter baumannii isolates from four hospitals in Washington DC. The antibiotic susceptibility of the isolates was determined by VITEK 2 analyses, while PCR was used to examine the presence of antibiotic-resistant genes and mobile genetic elements. Trilocus multiplex-PCR was used along with pulsed-field gel electrophoresis (PFGE) for strain typing and for accessing clonal relationships among the isolates. Antimicrobial susceptibility testing indicated that 46% of the isolates were carbapenem-resistant and possessed MDR and XDR phenotypes. PFGE clustered the 28 isolates into seven clonal (C1–C7) complexes based on >75% similarity cut-off. Thirty-six percent of the isolates belonged to international clone II, while 29% were assigned to Group 4 by trilocus multiplex-PCR. Although the blaOXA-51-like gene was found in all the isolates, only 36% were positive for the blaOXA-23-like gene. PCR analysis also found a metallo-β-lactamase (MBL) gene (blaVIM) in 71% of the isolates. Of the 13 CR isolates, 8 were PCR positive for both blaVIM and blaOXA-23-like genes, while 5 harbored only blaVIM gene. This study revealed the emergence of VIM carbapenemase-producing A. baumannii isolates, which has not been previously reported in the United States.

scholarly journals Activity of cefiderocol against high-risk clones of multidrug-resistant Enterobacterales, Acinetobacter baumannii, Pseudomonas aeruginosa and Stenotrophomonas maltophilia

2020 ◽  
Vol 75 (7) ◽  
pp. 1840-1849 ◽  
Author(s):  
Mercedes Delgado-Valverde ◽  
M del Carmen Conejo ◽  
Lara Serrano ◽  
Felipe Fernández-Cuenca ◽  
Álvaro Pascual
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acinetobacter Baumannii ◽  
Stenotrophomonas Maltophilia ◽  
Enterobacter Cloacae ◽  
Multidrug Resistant ◽  
In Vitro Activity ◽  
Carbapenem Resistant ◽  
Excellent Activity ◽  
In Vitro Antibacterial Activity

Abstract Background Cefiderocol is a novel siderophore cephalosporin, developed for activity against MDR Gram-negative bacilli (MDR-GNB). Objectives To assess the in vitro antibacterial activity of cefiderocol against a collection of MDR-GNB clinical isolates from hospitals in southern Spain. Methods Two hundred and thirty-one isolates of successful clones were tested: 125 Enterobacterales (121 ESBL- and/or carbapenemase-producing Klebsiella pneumoniae and 4 carbapenemase-producing Enterobacter cloacae), 80 Acinetobacter baumannii, 6 Pseudomonas aeruginosa and 20 Stenotrophomonas maltophilia. Ceftolozane/tazobactam, ceftazidime, ceftazidime/avibactam, cefepime, aztreonam, meropenem, amikacin, ciprofloxacin, colistin and tigecycline were used as comparators against Enterobacterales, P. aeruginosa and A. baumannii. Minocycline, levofloxacin and trimethoprim/sulfamethoxazole were studied against S. maltophilia instead of aztreonam, ciprofloxacin and cefepime. MICs were determined by broth microdilution according to CLSI guidelines. MIC determination was performed in CAMHB for all antimicrobials except cefiderocol, where iron-depleted CAMHB was used. Results Cefiderocol showed potent in vitro activity against the isolates analysed. MIC50 and MIC90 values were in the ranges 0.125–8 mg/L and 0.5–8 mg/L, respectively, and 98% of isolates were inhibited at ≤4 mg/L. Only five isolates showed cefiderocol MICs of >4 mg/L: three ST2/OXA-24/40-producing A. baumannii, one ST114/VIM-1-producing E. cloacae and one ST114/VIM-1 + OXA-48-producing E. cloacae. All KPC-3-producing K. pneumoniae were susceptible to cefiderocol, even those resistant to ceftazidime/avibactam. P. aeruginosa isolates showed cefiderocol MICs of <4 mg/L, including those resistant to ceftolozane/tazobactam. S. maltophilia isolates displayed cefiderocol MICs of <4 mg/L, including those resistant to levofloxacin and/or trimethoprim/sulfamethoxazole. Conclusions Cefiderocol showed excellent activity against MDR-GNB, including carbapenem-resistant isolates, and was the most active antimicrobial tested against this collection.

scholarly journals ARGONAUT-I: Activity of Cefiderocol (S-649266), a Siderophore Cephalosporin, against Gram-Negative Bacteria, Including Carbapenem-Resistant Nonfermenters and Enterobacteriaceae with Defined Extended-Spectrum β-Lactamases and Carbapenemases

2018 ◽  
Vol 63 (1) ◽  
Author(s):  
Michael R. Jacobs ◽  
Ayman M. Abdelhamed ◽  
Caryn E. Good ◽  
Daniel D. Rhoads ◽  
Kristine M. Hujer ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acinetobacter Baumannii ◽  
Stenotrophomonas Maltophilia ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Extended Spectrum ◽  
Mueller Hinton ◽  
Mueller Hinton Broth

ABSTRACT The activity of the siderophore cephalosporin cefiderocol is targeted against carbapenem-resistant Gram-negative bacteria. In this study, the activity of cefiderocol against characterized carbapenem-resistant Acinetobacter baumannii complex, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, and Enterobacteriaceae strains was determined by microdilution in iron-depleted Mueller-Hinton broth. The MIC90s against A. baumannii, S. maltophilia, and P. aeruginosa were 1, 0.25, and 0.5 mg/liter, respectively. Against Enterobacteriaceae, the MIC90 was 1 mg/liter for the group harboring OXA-48-like, 2 mg/liter for the group harboring KPC-3, and 8 mg/liter for the group harboring TEM/SHV ESBL, NDM, and KPC-2.

scholarly journals Activity of β-lactam/taniborbactam (VNRX-5133) combinations against carbapenem-resistant Gram-negative bacteria

2020 ◽  
Vol 76 (1) ◽  
pp. 160-170
Author(s):  
Shazad Mushtaq ◽  
Anna Vickers ◽  
Michel Doumith ◽  
Matthew J Ellington ◽  
Neil Woodford ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Stenotrophomonas Maltophilia ◽  
Clinical Development ◽  
Published Data ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Class A ◽  
Carbapenem Resistant ◽  
Elizabethkingia Meningoseptica

Abstract Background Boronates are of growing interest as β-lactamase inhibitors. The only marketed analogue, vaborbactam, principally targets KPC carbapenemases, but taniborbactam (VNRX-5133, Venatorx) has a broader spectrum. Methods MICs of cefepime and meropenem were determined combined with taniborbactam or avibactam for carbapenem-resistant UK isolates. β-Lactamase genes and porin alterations were sought by PCR or sequencing. Results Taniborbactam potentiated partner β-lactams against: (i) Enterobacterales with KPC, other class A, OXA-48-like, VIM and NDM (not IMP) carbapenemases; and (ii) Enterobacterales inferred to have combinations of ESBL or AmpC activity and impermeability. Potentiation of cefepime (the partner for clinical development) by taniborbactam was slightly weaker than by avibactam for Enterobacterales with KPC or OXA-48-like carbapenemases, but MICs of cefepime/taniborbactam were similar to those of ceftazidime/avibactam, and the spectrum was wider. MICs of cefepime/taniborbactam nonetheless remained >8 + 4 mg/L for 22%–32% of NDM-producing Enterobacterales. Correlates of raised cefepime/taniborbactam MICs among these NDM Enterobacterales were a cefepime MIC >128 mg/L, particular STs and, for Escherichia coli only: (i) the particular blaNDM variant (even though published data suggest all variants are inhibited similarly); (ii) inserts in PBP3; and (iii) raised aztreonam/avibactam MICs. Little or no potentiation of cefepime or meropenem was seen for Pseudomonas aeruginosa and Acinetobacter baumannii with MBLs, probably reflecting slower uptake or stronger efflux. Potentiation of cefepime was seen for Stenotrophomonas maltophilia and Elizabethkingia meningoseptica, which have both chromosomal ESBLs and MBLs. Conclusions Taniborbactam broadly reversed cefepime or meropenem non-susceptibility in Enterobacterales and, less reliably, in non-fermenters.

scholarly journals Tigecycline Versus Colistin in the Treatment of Carbapenem-resistant Acinetobacter baumannii Complex Osteomyelitis

2020 ◽  
Vol 5 (2) ◽  
pp. 60-66
Author(s):  
Priscila R. Oliveira ◽  
Vladimir C. Carvalho ◽  
Eduardo S. Saconi ◽  
Marcos C. Leonhardt ◽  
Kodi E. Kojima ◽  
...  
Keyword(s):  
Adverse Events ◽  
Acinetobacter Baumannii ◽  
Chronic Osteomyelitis ◽  
Tertiary Hospital ◽  
Antimicrobial Treatment ◽  
Duration Of Therapy ◽  
Carbapenem Resistant ◽  
Significant Difference ◽  
Acinetobacter Baumannii Complex

Abstract. Background: Acinetobacter baumannii complex is an increasingly important cause of osteomyelitis. It is considered a difficult to treat agent, due to increasing antimicrobial resistance and few available therapeutic options.Objective: To compare effectiveness and tolerability of tigecycline and colistin in patients with osteomyelitis caused by carbapenem-resistant A. baumannii complex (CRABC).Methods: This retrospective review included all patients admitted to a 150-bed tertiary hospital from 2007 to 2015 with microbiologically confirmed CRABC osteomyelitis for which they received tigecycline or colistin. Data on demographic and clinical characteristics, adverse events, and outcomes 12 months after the end of antimicrobial treatment were analysed and stratified according to the antimicrobial used.Results: 65 patients were included, 34 treated with colistin and 31 with tigecycline. There were significantly more men (P = 0.028) in the colistin group, and more smokers (P = 0.021) and greater occurrence of chronic osteomyelitis (P = 0.036) in the tigecycline treatment group. Median duration of therapy was 42.5 days for colistin and 42 days for tigecycline, with no significant difference. Overall incidence of adverse events was higher in the colistin group (P = 0.047). In particular, incidence of renal impairment was also higher in this group (P = 0.003). Nausea and vomiting were more frequent with tigecycline (P = 0.046). There were no significant differences between groups in relapse, amputation, or death.Conclusions: Tigecycline had a better safety profile than colistin in the treatment of osteomyelitis due to CRABC, with no significant difference in outcomes after 12 months of follow-up.

scholarly journals In Vitro Activity of KBP-7072, a Novel Third-Generation Tetracycline, against 531 Recent Geographically Diverse and Molecularly Characterized Acinetobacter baumannii Species Complex Isolates

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Michael D. Huband ◽  
Rodrigo E. Mendes ◽  
Michael A. Pfaller ◽  
Jill M. Lindley ◽  
Gregory J. Strand ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Species Complex ◽  
Phase 1 ◽  
The United States ◽  
Clinical Development ◽  
Asia Pacific ◽  
Third Generation ◽  
Content Type ◽  
Carbapenem Resistant

ABSTRACT KBP-7072 is a novel third-generation tetracycline (aminomethylcycline) antibacterial that overcomes common efflux and ribosomal protection resistance mechanisms that cause resistance in older-generation tetracyclines. KBP-7072 completed phase 1 clinical development studies for safety, tolerability, and pharmacokinetics (ClinicalTrials.gov identifier NCT02454361) and multiple ascending doses in healthy subjects (ClinicalTrials.gov identifier NCT02654626) in December 2015. Both oral and intravenous formulations of KBP-7072 are being developed. In this study, we evaluated the in vitro activities of KBP-7072 and comparator agents by CLSI document M07 (2018) broth microdilution against 531 recent geographically diverse and/or molecularly characterized Acinetobacter baumannii-A. calcoaceticus species complex (A. baumannii) isolates from the United States, Europe, Asia-Pacific (excluding China), and Latin America. A. baumannii isolates included carbapenem-resistant, colistin-resistant, tetracycline-resistant, and extended-spectrum-β-lactamase (ESBL)- and metallo-β-lactamase (MBL)-producing isolates. Overall, KBP-7072 (MIC50/90, 0.25/1 mg/liter) was comparable in activity to colistin (92.8%/92.8% susceptible [S] [CLSI/EUCAST]) against A. baumannii isolates, inhibiting 99.2% of isolates at ≤2 mg/liter and 97.6% of isolates at ≤1 mg/liter. KBP-7072 was equally active against A. baumannii isolates, including carbapenem-resistant, colistin-resistant, and tetracycline-resistant isolates, regardless of geographic location, and maintained activity against ESBL- and MBL-producing isolates. KBP-7072 outperformed comparator agents, including ceftazidime (40.3% S [CLSI]), gentamicin (48.2%/48.2% S [CLSI/EUCAST]), levofloxacin (39.5%/37.9% S [CLSI/EUCAST]), meropenem (42.0%/42.0% S [CLSI/EUCAST]), piperacillin-tazobactam (33.3% S [CLSI]), and all tetracycline-class comparator agents, which include doxycycline (67.3% S [CLSI]), minocycline (73.8% S [CLSI]), tetracycline (37.2% S [CLSI]), and tigecycline (79.5% inhibited by ≤2 mg/liter). The potent in vitro activity of KBP-7072 against recent geographically diverse, molecularly characterized, and drug-resistant A. baumannii isolates supports continued clinical development for the treatment of serious infections, including those caused by A. baumannii.

Cefiderocol as Rescue Therapy for Acinetobacter baumannii and Other Carbapenem-resistant Gram-negative Infections in Intensive Care Unit Patients

2020 ◽  
Author(s):  
Marco Falcone ◽  
Giusy Tiseo ◽  
Manuela Nicastro ◽  
Alessandro Leonildi ◽  
Alessandra Vecchione ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Stenotrophomonas Maltophilia ◽  
Inhibitory Concentration ◽  
Clinical Success ◽  
Rescue Therapy ◽  
Survival Rates ◽  
New Delhi ◽  
Ventilator Associated Pneumonia ◽  
Gram Negative ◽  
Carbapenem Resistant

Abstract Ten critically ill patients with either bacteremia or ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii, Stenotrophomonas maltophilia, or New Delhi metallo-β-lactamase–producing Klebsiella pneumoniae received cefiderocol. All strains had minimum inhibitory concentration ≤2 μg/mL. Thirty-day clinical success and survival rates were 70% and 90%, respectively. Two patients had a microbiological failure. Future prospective studies are warranted.

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