scholarly journals Shifting Gears: The Future of Polymyxin Antibiotics

Antibiotics ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 42 ◽  
Author(s):  
Lenhard ◽  
Bulman ◽  
Tsuji ◽  
Kaye
Keyword(s):  
Treatment Options ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Carbapenem Resistant ◽  
The Future ◽  
Important Addition ◽  
Future Strategy ◽  
Future Utility ◽  
A Current

The manuscripts contained in this special edition of Antibiotics represent a current review of the polymyxins as well as highlights from the 3rd International Polymyxin Conference, which was held in Madrid, Spain, April 25 to 26, 2018. The role of the polymyxin antibiotics has evolved over time based on the availability of alternative agents. After high rates of nephrotoxicity caused the drug class to fall out of favor, polymyxins were once against utilized in the 21st century to combat drug-resistant pathogens. However, the introduction of safer agents with activity against drug-resistant organisms has brought the future utility of polymyxins into question. The present review investigates the future niche of polymyxins by evaluating currently available and future treatment options for difficult-to-treat pathogens. The introduction of ceftazidime-avibactam, meropenem-vaborbactam and plazomicin are likely to decrease polymyxin utilization for infections caused by Enterobacteriaceae. Similarly, the availability of ceftolozane-tazobactam will reduce the use of polymyxins to counter multidrug-resistant Pseudomonas aeruginosa. In contrast, polymyxins will likely continue be an important option for combatting carbapenem-resistant Acinetobacter baumannii until better options become commercially available. Measuring polymyxin concentrations in patients and individualizing therapy may be a future strategy to optimize clinical outcomes while minimizing nephrotoxicity. Inhaled polymyxins will continue to be an adjunctive option for pulmonary infections but further clinical trials are needed to clarify the efficacy of inhaled polymyxins. Lastly, safer polymyxin analogs will potentially be an important addition to the antimicrobial armamentarium.

scholarly journals Antibiotic Susceptibility of NDM-Producing Enterobacterales Collected in the United States in 2017 and 2018

2020 ◽  
Vol 64 (9) ◽  
Author(s):  
Joseph D. Lutgring ◽  
Rocío Balbuena ◽  
Natashia Reese ◽  
Sarah E. Gilbert ◽  
Uzma Ansari ◽  
...  
Keyword(s):  
United States ◽  
Antibiotic Susceptibility ◽  
Treatment Options ◽  
The United States ◽  
Multidrug Resistant ◽  
New Delhi ◽  
Drug Resistant ◽  
Carbapenem Resistant ◽  
Extensively Drug Resistant

ABSTRACT The treatment of infections caused by carbapenem-resistant Enterobacterales, especially New Delhi metallo-β-lactamase (NDM)-producing bacteria, is challenging. Although less common in the United States than some other carbapenemase producers, NDM-producing bacteria are a public health threat due to the limited treatment options available. Here, we report on the antibiotic susceptibility of 275 contemporary NDM-producing Enterobacterales collected from 30 U.S. states through the Centers for Disease Control and Prevention’s Antibiotic Resistance Laboratory Network. The aims of the study were to determine the susceptibility of these isolates to 32 currently available antibiotics using reference broth microdilution and to explore the in vitro activity of 3 combination agents that are not yet available. Categorical interpretations were determined using Clinical and Laboratory Standards Institute (CLSI) interpretive criteria. For agents without CLSI criteria, Food and Drug Administration (FDA) interpretive criteria were used. The percentage of susceptible isolates did not exceed 90% for any of the FDA-approved antibiotics tested. The antibiotics with breakpoints that had the highest in vitro activity were tigecycline (86.5% susceptible), eravacycline (66.2% susceptible), and omadacycline (59.6% susceptible); 18.2% of isolates were susceptible to aztreonam. All NDM-producing isolates tested were multidrug resistant, and 116 isolates were extensively drug resistant (42.2%); 207 (75.3%) isolates displayed difficult-to-treat resistance. The difficulty in treating infections caused by NDM-producing Enterobacterales highlights the need for containment and prevention efforts to keep these infections from becoming more common.

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

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.

scholarly journals The Biology and Role of Interleukin-32 in Tuberculosis

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Wu Li ◽  
Wanyan Deng ◽  
Jianping Xie
Keyword(s):  
Multidrug Resistant ◽  
Drug Resistant ◽  
Host Molecule ◽  
Tuberculosis Control ◽  
Promising Alternative ◽  
Extensively Drug Resistant ◽  
Important Host ◽  
Resistant Strains ◽  
Drug Resistant Strains

Tuberculosis, caused by Mycobacterium tuberculosis, remains a leading cause of morbidity and mortality globally, with nearly 10.4 million new cases of incidence and over 1.7 million deaths annually. Drug-resistant M. tuberculosis strains, especially multidrug-resistant or extensively drug-resistant strains, have further intensified the problem associated with tuberculosis control. Host-directed therapy is a promising alternative for tuberculosis control. IL-32 is increasingly recognized as an important host molecule against tuberculosis. In this review, we highlight the proinflammatory properties of IL-32 and the mode of action of IL-32 in mycobacterial infections to inspire the development of novel immunity-based countermeasures and host-directed therapies against tuberculosis.

Detection of extensively drug-resistant and hypervirulent Klebsiella pneumoniae ST15, ST147, ST377 and ST442 in Iran

2021 ◽  
Author(s):  
Sara Davoudabadi ◽  
Hossein Goudarzi ◽  
Mehdi Goudarzi ◽  
Abdollah Ardebili ◽  
Ebrahim Faghihloo ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Pcr Amplification ◽  
Multidrug Resistant ◽  
Diffusion Method ◽  
Drug Resistant ◽  
Carbapenem Resistant ◽  
Extensively Drug Resistant ◽  
String Test ◽  
Pcr Method ◽  
Extensively Drug Resistance

Abstract In this study, we focused on the emergence of extensively drug-resistant (XDR), pandrug-resistant (PDR), and hypervirulent Klebsiella pneumoniae (hvKP) in Iran. During 2018 to 2020 a total of 52 K. pneumoniae isolates were collected from different clinical specimens. The hvKP isolates were identified by PCR amplification of virulence and capsular serotype-specific genes. Hypermucoviscous K. pneumoniae (hmKP) were identified by string test. Carbapenem-resistant hvKP (CR-hvKP), multidrug-resistant hvKP (MDR-hvKP), extensively drug-resistant hvKP (XDR-hvKP), and pandrug-resistant hvKP (PDR-hvKP) were determined by disc diffusion method, Carba-NP test and PCR method. XDR-hvKP isolates were typed by multilocus sequence typing (MLST). Among all K. pneumoniae isolates 14 (26.9%) were identified as hvKP and 78.6% (11/14) of them were hmKP however, none of the classic K. pneumoniae (cKP) isolates were hmKP. The predominant capsular serotype of hvKP was K2 (42.85%) followed by K1 (35.71%). The prevalence of MDR-hvKP, XDR-hvKP and PDR-hvKP isolates were 6 (42.9%), 5 (35.7%) and 1 (7.1%), respectively. ESBL production was found in 85.7% of hvKP isolates and most of them carried bla TEM gene (78.6%) and 6 isolates (42.9%) were CR-hvKP. Among hvKP isolates, 1 (7.1%), 2 (14.3%), 3 (21.4%), 8 (28.6%), and 11 (78.6%) carried bla NDM-6, bla OXA-48, bla CTX-M, bla SHV, and bla TEM genes, respectively. According to MLST analysis, 2, 1, 1, and 1 XDR-hvKP isolates belonged to ST15, ST377, ST442, and ST147, respectively. The occurrence of such isolates is deeply concerning due to the combination of hypervirulence and extensively drug-resistance or pandrug-resistance.

scholarly journals Synergistic Activity of Colistin-Containing Combinations against Colistin-ResistantEnterobacteriaceae

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Thea Brennan-Krohn ◽  
Alejandro Pironti ◽  
James E. Kirby
Keyword(s):  
Treatment Options ◽  
Multidrug Resistant ◽  
Synergistic Activity ◽  
Gram Negative ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Resistant Strains ◽  
Bacterial Outer Membrane ◽  
Time Kill ◽  
Synergistic Combinations

ABSTRACTResistance to colistin, a polypeptide drug used as an agent of last resort for the treatment of infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria, including carbapenem-resistantEnterobacteriaceae(CRE), severely limits treatment options and may even transform an XDR organism into one that is pan-resistant. We investigated the synergistic activity of colistin in combination with 19 antibiotics against a collection of 20 colistin-resistantEnterobacteriaceaeisolates, 15 of which were also CRE. All combinations were tested against all strains using an inkjet printer-assisted digital dispensing checkerboard array, and the activities of those that demonstrated synergy by this method were evaluated against a single isolate in a time-kill synergy study. Eighteen of 19 combinations demonstrated synergy against two or more isolates, and the 4 most highly synergistic combinations (colistin combined with linezolid, rifampin, azithromycin, and fusidic acid) were synergistic against ≥90% of strains. Sixteen of 18 combinations (88.9%) that were synergistic in the checkerboard array were also synergistic in a time-kill study. Our findings demonstrate that colistin in combination with a range of antibiotics, particularly protein and RNA synthesis inhibitors, exhibits synergy against colistin-resistant strains, suggesting that colistin may exert a subinhibitory permeabilizing effect on the Gram-negative bacterial outer membrane even in isolates that are resistant to it. These findings suggest that colistin combination therapy may have promise as a treatment approach for patients infected with colistin-resistant XDR Gram-negative pathogens.

scholarly journals Treatment Options for Carbapenem-resistant Gram-negative Bacterial Infections

2019 ◽  
Vol 69 (Supplement_7) ◽  
pp. S565-S575 ◽  
Author(s):  
Yohei Doi
Keyword(s):  
Bacterial Infections ◽  
Treatment Options ◽  
Clinical Development ◽  
Gram Negative Bacteria ◽  
First Line ◽  
Safe Alternative ◽  
New Agents ◽  
Gram Negative ◽  
Carbapenem Resistant

AbstractAntimicrobial resistance has become one of the greatest threats to public health, with rising resistance to carbapenems being a particular concern due to the lack of effective and safe alternative treatment options. Carbapenem-resistant gram-negative bacteria of clinical relevance include the Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, and more recently, Stenotrophomonas maltophilia. Colistin and tigecycline have been used as first-line agents for the treatment of infections caused by these pathogens; however, there are uncertainties regarding their efficacy even when used in combination with other agents. More recently, several new agents with activity against certain carbapenem-resistant pathogens have been approved for clinical use or are reaching late-stage clinical development. They include ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, plazomicin, eravacycline, and cefiderocol. In addition, fosfomycin has been redeveloped in a new intravenous formulation. Data regarding the clinical efficacy of these new agents specific to infections caused by carbapenem-resistant pathogens are slowly emerging and appear to generally favor newer agents over previous best available therapy. As more treatment options become widely available for carbapenem-resistant gram-negative infections, the role of antimicrobial stewardship will become crucial in ensuring appropriate and rationale use of these new agents.

scholarly journals Carbapenemase Genes and Multidrug Resistance of Acinetobacter Baumannii: A Cross Sectional Study of Patients with Pneumonia in Southern Vietnam

Antibiotics ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 148 ◽  
Author(s):  
Cuong Hoang Quoc ◽  
Thao Nguyen Thi Phuong ◽  
Hai Nguyen Duc ◽  
Trung Tran Le ◽  
Hang Tran Thi Thu ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Acinetobacter Baumannii ◽  
Demographic Data ◽  
Treatment Options ◽  
Bacterial Pathogen ◽  
Multidrug Resistant ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Carbapenem Resistant ◽  
Hospital Acquired

Background: Acinetobacter baumannii (Ab) is an opportunistic bacterial pathogen found in hospital-acquired infections including nosocomial pneumonia, especially multidrug-resistant Ab. This study aims to survey the drug resistance profiles of Ab isolated from patients in Thong Nhat Dong Nai General Hospital and assess the relationship between genotypes and antibiotic resistance; Methods: Ninety-seven Ab strains isolated from 340 lower respiratory tract specimens among pneumonia patients were used to screen the most common local carbapenemase genes. Antimicrobial susceptibility testing results and demographic data were collected and minimum inhibitory concentrations (MIC) of colistin were also determined; Results: Over 80% and 90% of Ab strains were determined as carbapenem-resistant and multidrug-resistant (MDR), respectively. Most of the strains carried carbapenemase genes, including blaOXA-51, blaOXA-23-like, blaOXA-58-like, and blaNDM-1, with proportions of 97 (100%), 76 (78.4%), 10 (10.3%), 6 (6.2%), respectively. Amongst these genes, blaOXA-23-like was the only gene which significantly influenced the resistance (p < 0.0001); and Conclusions: The severity of Ab antibiotic resistance is urgent and specifically related to carbapenemase encoding genes. Therefore, screening of MDR Ab and carbapenemase for better treatment options is necessary.

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

2016 ◽  
Vol 3 (3) ◽  
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.

scholarly journals Emergence of DIM-1 and KPC-1 Genes Associated Carbapenem-Resistant Pseudomonas Aeruginosa Isolates in Three Major Hospitals in Hanoi, Vietnam (2010-2015)

2021 ◽  
Author(s):  
Tran Hai Anh ◽  
Tran Huy Hoang ◽  
Vu Thi Ngoc Bich ◽  
Trinh Son Tung ◽  
Tran Dieu Linh ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Phylogenetic Tree Analysis ◽  
Antibiotic Resistant ◽  
Hospital Acquired Infection ◽  
Healthcare Settings ◽  
Carbapenem Resistant ◽  
Hospital Acquired

Abstract Background: Multidrug-resistant bacteria including carbapenem resistant Pseudomonas aeruginosa are recognised as an important cause of hospital-acquired infections worldwide. To determine the molecular characterisation and antibiotic resistant genes associated with carbapenem-resistant P. aeruginosa. Methods: we conducted whole-genome sequencing and phylogenetic analysis of 72 carbapenem-resistant P. aeruginosa isolated from hospital-acquired infection patients from 2010 to 2015 in three major hospitals in Hanoi, Vietnam. Results: We identified three variants of IMP genes, among which IMP-15 gene was the most frequent (n= 34) in comparison to IMP-26 (n= 2) and IMP-51 (n=12). We observed two isolates with imipenem MIC >128mg/L that co-harboured IMP-15 and DIM-1 genes and seven isolates (imipenem MIC> 128mg/L) with KPC-1 gene from the same hospital. MLST data showed that sequence types (ST) of 72 isolates were classified into 18 STs and phylogenetic tree analysis divided these isolates into nine groups. Conclusion: Our results provide evidence that not only IMP-26, but other variants of IMPs like IMP-15 and IMP-51 genes and several STs (ST235, ST244, ST277, ST310, ST773 and ST3151) have been disseminated in health care settings in Vietnam. Also, we report the first finding in Vietnam that two isolates belonging to ST1240 and ST3340 harboured two important carbapenemase genes (IMP-15 and, DIM-1) and seven isolates belonging to ST3151 of P. aeruginosa carried the KPC-1 gene, which could be a potential cause of seriously restricted available treatment options in healthcare settings.

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