Infections Due to Acinetobacter baumannii in the ICU: Treatment Options

AbstractBacteria within the genus Acinetobacter (principally A. baumannii-calcoaceticus complex [ABC]) are gram-negative coccobacilli that may cause nosocomial infections in critically ill or debilitated patients (particularly ventilator-associated pneumonia and infections of the bloodstream, urinary tract, and wounds). Treatment of Acinetobacter infections is difficult, as Acinetobacter spp. are intrinsically resistant to multiple antimicrobial agents, and have a remarkable ability to acquire new resistance determinants via mechanisms that include plasmids, transposons, integrons, and resistance islands. Since the 1990s, global resistance to antimicrobials has escalated dramatically among ABC. Global spread of multidrug-resistant (MDR)-A. baumannii strains reflects dissemination of a few clones between hospitals, geographic regions, and continents; excessive use of antibiotics amplifies this spread. Many isolates are resistant to all antimicrobials except colistin (polymyxin E) and tigecycline, and some infections are untreatable with existing antimicrobial agents. Antimicrobial resistance poses a serious threat to treat or prevent infections due to ABC. Strategies to curtail environmental colonization with MDR-ABD will require aggressive infection control efforts and cohorting of infected patients. Thoughtful antibiotic strategies are essential to limit the spread of MDR-ABC. Optimal therapy will likely require combination antimicrobial therapy of existing antibiotics as well as development of novel antibiotic classes.

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Resistance to colistin in Klebsiella pneumoniae: a 4.0 strain?

Infectious Disease Reports ◽

10.4081/idr.2017.7104 ◽

2017 ◽

Vol 9 (2) ◽

Cited By ~ 13

Author(s):

Guido Granata ◽

Nicola Petrosillo

Keyword(s):

Infection Prevention ◽

Antimicrobial Agents ◽

Treatment Options ◽

Multidrug Resistant ◽

New Agents ◽

Gram Negative ◽

Beta Lactamases ◽

Carbapenem Resistant ◽

Chromosomal Genes ◽

Global Spread

The global rise of multidrug-resistant gram-negative bacteria represents an increasing threat to patient safety. From the first observation of a carbapenem-resistant gramnegative bacteria a global spread of extendedspectrum beta-lactamases and carbapenemases producing Klebsiella pneumoniae has been observed. Treatment options for multidrug-resistant K. pneumoniae are actually limited to combination therapy with some aminoglycosides, tigecycline and to older antimicrobial agents. Unfortunately, the prevalence of colistin-resistant and tigecycline- resistant K. pneumoniae is increasing globally. Infection due to colistin-resistant K. pneumoniae represents an independent risk factor for mortality. Resistance to colistin in K. pneumoniae may be multifactorial, as it is mediated by chromosomal genes or plasmids. The emergence of transmissible, plasmidmediated colistin resistance is an alarming finding. The absence of new agents effective against resistant Gram-negative pathogens means that enhanced surveillance, compliance with infection prevention procedures, and antimicrobial stewardship programs will be required to limit the spread of colistinresistant K. pneumoniae.

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Genomic Insights Into Last-Line Antimicrobial Resistance in Multidrug-Resistant Staphylococcus and Vancomycin-Resistant Enterococcus

Frontiers in Microbiology ◽

10.3389/fmicb.2021.637656 ◽

2021 ◽

Vol 12 ◽

Author(s):

Adrianna M. Turner ◽

Jean Y. H. Lee ◽

Claire L. Gorrie ◽

Benjamin P. Howden ◽

Glen P. Carter

Keyword(s):

Molecular Mechanisms ◽

Antimicrobial Agents ◽

Treatment Options ◽

Multidrug Resistant ◽

Vancomycin Resistant Enterococcus ◽

Human Pathogens ◽

Mechanisms Of Resistance ◽

Global Spread ◽

Vancomycin Resistant ◽

Emergence Of Resistance

Multidrug-resistant Staphylococcus and vancomycin-resistant Enterococcus (VRE) are important human pathogens that are resistant to most clinical antibiotics. Treatment options are limited and often require the use of ‘last-line’ antimicrobials such as linezolid, daptomycin, and in the case of Staphylococcus, also vancomycin. The emergence of resistance to these last-line antimicrobial agents is therefore of considerable clinical concern. This mini-review provides an overview of resistance to last-line antimicrobial agents in Staphylococcus and VRE, with a particular focus on how genomics has provided critical insights into the emergence of resistant clones, the molecular mechanisms of resistance, and the importance of mobile genetic elements in the global spread of resistance to linezolid.

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Resistance to nitrofurantoin is an indicator of extensive drug-resistant (XDR) Enterobacteriaceae

Journal of Medical Microbiology ◽

10.1099/jmm.0.001347 ◽

2021 ◽

Vol 70 (4) ◽

Author(s):

Balaram Khamari ◽

Prakash Kumar ◽

Bulagonda Eswarappa Pradeep

Keyword(s):

Antimicrobial Agents ◽

Efflux Pump ◽

Treatment Options ◽

Strong Association ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Resistant Bacteria ◽

Drug Resistant ◽

Content Type ◽

Link Type

Introduction. Nitrofurantoin is one of the preferred antibiotics in the treatment of uropathogenic multidrug-resistant (MDR) infections. However, resistance to nitrofurantoin in extensively drug-resistant (XDR) bacteria has severely limited the treatment options. Gap statement. Information related to co-resistance or collateral sensitivity (CS) with reference to nitrofurantoin resistant bacteria is limited. Aim. To study the potential of nitrofurantoin resistance as an indicator of the XDR phenotype in Enterobacteriaceae . Methods. One hundred (45 nitrofurantoin-resistant, 21 intermediately resistant and 34 nitrofurantoin-susceptible) Enterobacteriaceae were analysed in this study. Antibiotic susceptibility testing (AST) against nitrofurantoin and 17 other antimicrobial agents across eight different classes was performed by using the Vitek 2.0 system. The isolates were screened for the prevalence of acquired antimicrobial resistance (AMR) and efflux pump genes by PCR. Results. In total, 51 % of nitrofurantoin-resistant and 28 % of intermediately nitrofurantoin resistant isolates exhibited XDR characteristics, while only 3 % of nitrofurantoin-sensitive isolates were XDR (P=0.0001). Significant co-resistance was observed between nitrofurantoin and other tested antibiotics (β-lactam, cephalosporin, carbapenem, aminoglycoside and tetracycline). Further, the prevalence of AMR and efflux pump genes was higher in the nitrofurantoin-resistant strains compared to the susceptible isolates. A strong association was observed between nitrofurantoin resistance and the presence of bla PER-1, bla NDM-1, bla OXA-48, ant(2) and oqxA-oqxB genes. Tigecycline (84 %) and colistin (95 %) were the only antibiotics to which the majority of the isolates were susceptible. Conclusion. Nitrofurantoin resistance could be an indicator of the XDR phenotype among Enterobacteriaceae , harbouring multiple AMR and efflux pump genes. Tigecycline and colistin are the only antibiotics that could be used in the treatment of such XDR infections. A deeper understanding of the co-resistance mechanisms in XDR pathogens and prescription of AST-based appropriate combination therapy may help mitigate this problem.

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Acinetobacter species in laboratory mice: species survey and antimicrobial resistance

Laboratory Animals ◽

10.1177/0023677218818598 ◽

2018 ◽

Vol 53 (5) ◽

pp. 470-477

Author(s):

Laurentiu Benga ◽

Andrea T. Feßler ◽

W. Peter M. Benten ◽

Eva Engelhardt ◽

Karl Köhrer ◽

...

Keyword(s):

Antimicrobial Agents ◽

Inhibitory Concentration ◽

Rpob Gene ◽

Multidrug Resistant ◽

Laboratory Mice ◽

Hospital Epidemiology ◽

Acinetobacter Species ◽

Acinetobacter Spp ◽

Susceptibility Profiles ◽

Very High

The extra-hospital epidemiology of Acinetobacter infections is a subject of debate. In recent years, the prevalence of animal multidrug-resistant Acinetobacter infections has increased considerably. The goal of the present study was to specify Acinetobacter species isolated from laboratory mice and to test them for their antimicrobial susceptibility. During routine microbiological monitoring of laboratory mice, 12 Acinetobacter spp. were isolated. By means of 16S rRNA and rpoB gene sequencing, seven of the isolates were identified as Acinetobacter radioresistens, three isolates belonged to Acinetobacter genomospecies 14BJ, one isolate was classified as Acinetobacter pitii and one as Acinetobacter sp. ANC 4051. The distribution of the minimal inhibitory concentration (MIC) values was uniform for 21 of the 23 antimicrobial agents tested, whereas a broad MIC distribution was recorded for tulathromycin and streptomycin. The MIC values recorded were low for the majority of the antibiotics tested. Nevertheless, very high MIC values, which will probably render a therapeutic approach using these substances unsuccessful, were recorded for florfenicol, tiamulin, tilmicosin and cephalothin in most of the isolates. In conclusion, we document colonization of laboratory mice with different Acinetobacter species, displaying similar antibiotic susceptibility profiles, with possible implications in the Acinetobacter epidemiology as well as in the husbandry and experimentation of the colonized animals.

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Emerging Treatment Options for Infections by Multidrug-Resistant Gram-Positive Microorganisms

Microorganisms ◽

10.3390/microorganisms8020191 ◽

2020 ◽

Vol 8 (2) ◽

pp. 191 ◽

Cited By ~ 4

Author(s):

Despoina Koulenti ◽

Elena Xu ◽

Andrew Song ◽

Isaac Yin Sum Mok ◽

Drosos E. Karageorgopoulos ◽

...

Keyword(s):

Safety Profile ◽

Bacterial Infections ◽

Antimicrobial Agents ◽

Treatment Options ◽

Multidrug Resistant ◽

Current Treatment ◽

Multi Drug Resistance ◽

Gram Positive ◽

Treatment Regimens ◽

Gram Positive Bacteria

Antimicrobial agents are currently the mainstay of treatment for bacterial infections worldwide. However, due to the increased use of antimicrobials in both human and animal medicine, pathogens have now evolved to possess high levels of multi-drug resistance, leading to the persistence and spread of difficult-to-treat infections. Several current antibacterial agents active against Gram-positive bacteria will be rendered useless in the face of increasing resistance rates. There are several emerging antibiotics under development, some of which have been shown to be more effective with an improved safety profile than current treatment regimens against Gram-positive bacteria. We will extensively discuss these antibiotics under clinical development (phase I-III clinical trials) to combat Gram-positive bacteria, such as Staphylococcus aureus, Enterococcus faecium and Streptococcus pneumoniae. We will delve into the mechanism of actions, microbiological spectrum, and, where available, the pharmacokinetics, safety profile, and efficacy of these drugs, aiming to provide a comprehensive review to the involved stakeholders.

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Noninferior Antibiotics: When Is “Not Bad” “Good Enough”?

Open Forum Infectious Diseases ◽

10.1093/ofid/ofw110 ◽

2016 ◽

Vol 3 (3) ◽

Cited By ~ 5

Author(s):

Mark J. DiNubile

Keyword(s):

Nursing Home ◽

Clinical Practice ◽

Antimicrobial Agents ◽

Treatment Options ◽

Chronically Ill ◽

Multidrug Resistant ◽

Everyday Clinical Practice ◽

Novel Treatment ◽

Efficacious Treatment

Abstract Novel treatment options are urgently needed for patients with serious multidrug-resistant infections seen increasingly in routine everyday clinical practice, both in the hospital and nursing home as well as in the clinic and office setting. Unfortunately, the problem is no longer confined to chronically ill, repeatedly hospitalized patients. This essay explores the role of noninferiorly studies in addressing the pressing need for new antimicrobial agents to combat the emerging “superbugs”, calling attention to the nuances of interpreting their sometimes less-than-straightforward results. The overriding aim is not to find better antibiotics for routinely treatable infections but to identify safe and efficacious treatment options where none presently exist.

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Pathogenesis-Targeted Preventive Strategies for Multidrug Resistant Ventilator-Associated Pneumonia: A Narrative Review

Microorganisms ◽

10.3390/microorganisms8060821 ◽

2020 ◽

Vol 8 (6) ◽

pp. 821 ◽

Cited By ~ 1

Author(s):

Antonella Cotoia ◽

Savino Spadaro ◽

Guido Gambetti ◽

Despoina Koulenti ◽

Gilda Cinnella

Keyword(s):

Treatment Options ◽

Multidrug Resistant ◽

Convincing Evidence ◽

Narrative Review ◽

Ventilator Associated Pneumonia ◽

Effective Prevention ◽

Hospital Acquired Infection ◽

Effective Combination ◽

Oral Decontamination ◽

Hospital Acquired

Ventilator-associated pneumonia (VAP) is the most common hospital-acquired infection in the intensive care unit (ICU), accounting for relevant morbidity and mortality among critically ill patients, especially when caused by multidrug resistant (MDR) organisms. The rising problem of MDR etiologies, which has led to a reduction in treatment options, have increased clinician’s attention to the employment of effective prevention strategies. In this narrative review we summarized the evidence resulting from 27 original articles that were identified through a systematic database search of the last 15 years, focusing on several pathogenesis-targeted strategies which could help preventing MDR-VAP. Oral hygiene with Chlorhexidine (CHX), CHX body washing, selective oral decontamination (SOD) and/or digestive decontamination (SDD), multiple decontamination regimens, probiotics, subglottic secretions drainage (SSD), special cuff material and shape, silver-coated endotracheal tubes (ETTs), universal use of gloves and contact isolation, alcohol-based hand gel, vaporized hydrogen peroxide, and bundles of care have been addressed. The most convincing evidence came from interventions directly addressed against the key factors of MDR-VAP pathogenesis, especially when they are jointly implemented into bundles. Further research, however, is warranted to identify the most effective combination.

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A review on bacterial resistance to carbapenems: epidemiology, detection and treatment options

Future Science OA ◽

10.2144/fsoa-2019-0098 ◽

2020 ◽

Vol 6 (3) ◽

pp. FSO438 ◽

Cited By ~ 7

Author(s):

Ann A Elshamy ◽

Khaled M Aboshanab

Keyword(s):

Public Health ◽

Bacterial Resistance ◽

Antimicrobial Agents ◽

Treatment Options ◽

Carbapenem Resistance ◽

Multidrug Resistant ◽

Mechanisms Of Resistance ◽

Carbapenem Resistant ◽

Public Health Threat ◽

Carbapenem Resistant Enterobacteriaceae

Carbapenems are a class of antimicrobial agents reserved for infections caused by multidrug-resistant microorganisms. The emergence of carbapenem resistance has become a serious public health threat. This type of antimicrobial resistance is spreading at an alarming rate, resulting in major outbreaks and treatment failure of community-acquired and nosocomial infections caused by the clinically relevant carbapenem-producing Enterobacteriaceae or carbapenem-resistant Enterobacteriaceae. This review is focused on carbapenem resistance, including mechanisms of resistance, history and epidemiology, phenotypic and genotypic detection in the clinically relevant bacterial pathogens and the possible treatment options available.

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Multidrug-Resistant Acinetobacter baumannii Genetic Characterization and Spread in Lithuania in 2014, 2016, and 2018

Life ◽

10.3390/life11020151 ◽

2021 ◽

Vol 11 (2) ◽

pp. 151

Author(s):

Tatjana Kirtikliene ◽

Aistė Mierauskaitė ◽

Ilona Razmienė ◽

Nomeda Kuisiene

Keyword(s):

Acinetobacter Baumannii ◽

Resistance Genes ◽

Bacterial Infections ◽

Bacterial Resistance ◽

Antimicrobial Agents ◽

Variable Number Tandem Repeat ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Essential Information ◽

Acinetobacter Spp

Bacterial resistance to antimicrobial agents plays an important role in the treatment of bacterial infections in healthcare institutions. The spread of multidrug-resistant bacteria can occur during inter- and intra-hospital transmissions among patients and hospital personnel. For this reason, more studies must be conducted to understand how resistance occurs in bacteria and how it moves between hospitals by comparing data from different years and looking out for any patterns that might emerge. Multidrug-resistant (MDR) Acinetobacter spp. was studied at 14 healthcare institutions in Lithuania during 2014, 2016, and 2018 using samples from human bloodstream infections. In total, 194 isolates were collected and identified using MALDI-TOF and VITEK2 analyzers as Acinetobacter baumannii group bacteria. After that, the isolates were analyzed for the presence of different resistance genes (20 genes were analyzed) and characterized by using the Rep-PCR and MLVA (multiple-locus variable-number tandem repeat analysis) genotyping methods. The results of the study showed the relatedness of the different Acinetobacter spp. isolates and a possible circulation of resistance genes or profiles during the different years of the study. This study provides essential information, such as variability and diversity of resistance genes, genetic profiling, and clustering of isolates, to better understand the antimicrobial resistance patterns of Acinetobacter spp. These results can be used to strengthen the control of multidrug-resistant infections in healthcare institutions and to prevent potential outbreaks of this pathogen in the future.

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Case Commentary: Novel Therapy for Multidrug-Resistant Acinetobacter baumannii Infection

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01996-21 ◽

2021 ◽

Author(s):

Brianna M. Eales ◽

Vincent H. Tam

Keyword(s):

Multidrug Resistance ◽

Acinetobacter Baumannii ◽

Antimicrobial Agents ◽

Multidrug Resistant ◽

Pathogenic Bacterium ◽

Future Research ◽

Ventilator Associated Pneumonia ◽

Bacteriophage Therapy ◽

Novel Therapy ◽

Systemic Antibiotics

Acinetobacter baumannii is a pathogenic bacterium commonly associated with multidrug resistance. In this issue of Antimicrobial Agents and Chemotherapy , Rao et al. present a challenging case of ventilator-associated pneumonia in which bacteriophage therapy was used as a last resort treatment in combination with systemic antibiotics (S. Rao, M. Betancourt-Garcia, Y. O. Kare-Opaneye, B. E. Swiercezewski, et al., Antimicrob Agents Chemother, 2021, https://doi.org/10.1128/AAC.00824-21 ). The data are promising, and several key areas are highlighted for future research.

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