Carbapenem-resistant <em>Enterobacteriaceae</em> (CRE) and gram-negative bacterial  infections  in  south-west  Nigeria:  a  retrospective epidemiological surveillance study

Carbapenems are beta-lactam drugs that have broadest spectrum of activity. They are commonly used as the drugs of last resort to treat complicated bacterial infections. They bind to penicillin binding proteins (PBPs) and inhibit cell wall synthesis in bacteria. Important members that are in clinical use include doripenem, ertapenem, imipenem, and meropenem. Unlike other members, imipenem is hydrolyzed significantly by renal dehydropeptidase; therefore, it is administered together with an inhibitor of renal dehydropeptidase, cilastatin. Carbapenems are usually administered intravenously due to their low oral bioavailability. Most common side effects of these drugs include nausea, vomiting, diarrhea, skin rashes, and reactions at the infusion sites. Increasing resistance to these antibiotics is being reported throughout the world and is posing a threat to public health. Primary mechanisms of carbapenem resistance include expulsion of drug and inactivation of the drug by production of carbapenemases which may not only hydrolyze carbapenem, but also cephalosporin, penicillin, and aztreonam. Resistance especially among Gram negative bacteria is of much concern since there are only limited therapeutic options available for infections caused by carbapenem resistant Gram-negative bacterial pathogens. Commonly used drugs to treat such infections include polymyxins, fosfomycin and tigecycline.

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Treatment Options for Carbapenem-resistant Gram-negative Bacterial Infections

Clinical Infectious Diseases ◽

10.1093/cid/ciz830 ◽

2019 ◽

Vol 69 (Supplement_7) ◽

pp. S565-S575 ◽

Cited By ~ 36

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.

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Treatment of Multi-Drug Resistant Gram-Negative Bacterial Pathogenic Infections

Journal of Pure and Applied Microbiology ◽

10.22207/jpam.14.3.02 ◽

2020 ◽

Vol 14 (3) ◽

pp. 1639-1647

Author(s):

Wardah Mohammad Akram ◽

Godfred Antony Menezes ◽

Nida Abbas ◽

Wasim Ahmad ◽

Ahmed Mohamed Ahmed

Keyword(s):

Acinetobacter Baumannii ◽

Bacterial Infections ◽

Empirical Therapy ◽

Resistant Bacteria ◽

Drug Resistant ◽

Gram Negative ◽

Carbapenem Resistant ◽

Review Management ◽

Emergence Of Resistance ◽

Novel Therapeutic

The multidrug-resistant Gram-negative bacteria (MDR-GNB) infections in severely infected patients present numerous difficulties in terms of treatment failure where antibiotics cannot arrest such drug resistant bacteria. Based on the patient’s medical history and updated microbiological epidemiology data, an effective empirical treatment remains critical for optimal results to safeguard human health. The aim of this manuscript is to review management of MDR-Gram negative pathogenic bacterial infections. Quick diagnosis and narrow antimicrobial spectrum require rapid and timely diagnosis and effective laboratories in accordance with antimicrobial stewardship (AS) principles. Worldwide, there is an increased emergence of Carbapenem-resistant Enterobacteriaceae (CRE), Pseudomonas aeruginosa, and Acinetobacter baumannii. Recently, novel therapeutic options, such as meropenem/vaborbactam, ceftazidime/avibactam, ceftolozane/tazobactam, eravacycline and plazomicin became accessible to effectively counteract severe infections. Optimally using these delays the emergence of resistance to novel therapeutic agents. Further study is required, however, due to uncertainties in pharmacokinetic/pharmacodynamics optimization of dosages and therapeutic duration in severely ill patients. The novel agents should be verified for (i) action on carbapenem resistant Acinetobacter baumannii; (ii) action on CRE of β-lactam/β-lactamase inhibitors dependence on type of carbapenemase; (iii) emergence of resistance to novel antibacterials and dismiss selective pressure promoting development of resistance. Alternative treatments should be approached alike phage therapy or antibacterial peptides. The choice of empirical therapy is complicated by antibiotic resistance and can be combated by accurate antibiotic and their combinations usage, which is critical to patient survival. Noteworthy are local epidemiology, effective teamwork and antibiotic stewardship to guarantee that medications are utilized properly to counter the resistance.

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Etiology and Antimicrobial Resistance of Secondary Bacterial Infections in Patients Hospitalized With COVID-19 in Wuhan, China: A Retrospective Analysis

10.21203/rs.3.rs-47870/v1 ◽

2020 ◽

Author(s):

Jie Li ◽

Junwei Wang ◽

Yi Yang ◽

Peishan Cai ◽

Jingchao Cao ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Bacterial Infections ◽

Virus Disease ◽

Considerable Proportion ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Carbapenem Resistant ◽

Union Hospital ◽

Critical Patients ◽

Resistance Rates

Abstract Background: A considerable proportion of patients hospitalized with corona virus disease 2019 (COVID-19) have acquired secondary bacterial infections (SBIs). We report the etiology and antimicrobial resistance of bacteria to provide theoretical basis for appropriate infection therapy.Methods: In the retrospective study, we reviewed electronic medical records of all the patients hospitalized with COVID-19 in the Wuhan Union hospital from January 27 to March 17, 2020. According to the inclusion and exclusion criteria, patients who acquired SBIs were enrolled. Demographic, clinical course, etiology and antimicrobial resistance data of the SBIs were collected. Outcomes were also compared between patients who were classified as severe on admission and those who were classified as critical.Results: 6.8% (102/1495) of the patients with COVID-19 had acquired SBIs and almost half of them (50, 49.0%) died during hospitalization. Compared with the severe patients, the critical patients had a higher chance of SBIs. 159 strains of bacteria were isolated, 85.5% of which were Gram-negative bacteria. The top three bacteria of SBIs were A. baumannii (35.8%), K. pneumoniae (30.8%) and Staphylococcus (8.8%). The isolation rate of carbapenem-resistant A. baumannii and K. pneumoniae were 91.2% and 75.5%, respectively. Meticillin resistance was in 100% of Staphylococcus, and vancomycin resistance was not found. Conclusions: SBIs may occur in patients hospitalized with COVID-19 and lead to high mortality. The incidence of SBIs was associated with the grade on admission. Gram-negative bacteria, especially A. baumannii and K. pneumoniae, were the main bacteria and the resistance rates of the major isolated bacteria were generally high.

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Infections with Carbapenem-Resistant Gram-Negative Bacteria are a Serious Problem Among Critically Ill Children: A Single-Centre Retrospective Study

Pathogens ◽

10.3390/pathogens8020069 ◽

2019 ◽

Vol 8 (2) ◽

pp. 69 ◽

Cited By ~ 3

Author(s):

Fatih Aygun ◽

Fatma Deniz Aygun ◽

Fatih Varol ◽

Cansu Durak ◽

Haluk Çokuğraş ◽

...

Keyword(s):

Retrospective Study ◽

Critically Ill ◽

Bacterial Infections ◽

Invasive Mechanical Ventilation ◽

Critically Ill Children ◽

Resistant Bacteria ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Carbapenem Resistant ◽

Culture Positive

Children in paediatric intensive care units (PICUs) are vulnerable to infections because invasive devices are frequently used during their admission. We aimed to determine the prevalence, associated factors, and prognosis of infections in our PICU. This retrospective study evaluated culture results from 477 paediatric patients who were treated in the PICU between January 2014 and March 2019. Ninety patients (18.9%) had bacterial infections, with gram-negative bacteria being the predominant infectious agents. Culture-positive patients were younger than culture-negative patients, and age was related to mortality and various clinical factors. Culture-positive bacterial infections in the PICU were associated with increased use of invasive mechanical ventilation (odds ratio(OR); 2.254), red blood cell (RBC) transfusions (OR:2.624), and inotropic drugs (OR:2.262). Carbapenem resistance was found in approximately one-third of gram-negative bacteria, and was most common in tracheal aspirate specimens and cases involving Klebsiella spp. Total parenteral nutrition was a significant risk factor (OR:5.870). Positive blood culture results were associated with poorer patient survival than other culture results. These findings indicate that infections, especially those involving carbapenem-resistant bacteria, are an important issue when treating critically ill children.

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Cefiderocol for Extensively Drug-Resistant Gram-Negative Bacterial Infections: Real-world Experience From a Case Series and Review of the Literature

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa185 ◽

2020 ◽

Vol 7 (6) ◽

Cited By ~ 8

Author(s):

Sandra Zingg ◽

G Jacopo Nicoletti ◽

Sabine Kuster ◽

Milena Junker ◽

Andreas Widmer ◽

...

Keyword(s):

Bacterial Infections ◽

Case Reports ◽

Case Series ◽

Gram Negative Bacteria ◽

Drug Resistant ◽

Gram Negative ◽

Carbapenem Resistant ◽

Extensively Drug Resistant ◽

Health Care Associated Infections ◽

Tract Infections

Abstract Cefiderocol is a new siderophore cephalosporin with activity against carbapenem-resistant gram-negative bacteria. Data on its clinical efficacy are limited to complicated urinary tract infections. We present a series of 3 patients successfully treated with cefiderocol for complicated health care–associated infections and review published case reports.

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Clinical Experience with High-Dose Polymyxin B against Carbapenem-Resistant Gram-Negative Bacterial Infections—A Cohort Study

Antibiotics ◽

10.3390/antibiotics9080451 ◽

2020 ◽

Vol 9 (8) ◽

pp. 451

Author(s):

Yiying Cai ◽

Hui Leck ◽

Ray W. Tan ◽

Jocelyn Q. Teo ◽

Tze-Peng Lim ◽

...

Keyword(s):

Cohort Study ◽

Bacterial Infections ◽

Kidney Injury ◽

Polymyxin B ◽

Population Pharmacokinetic ◽

High Dose ◽

Pharmacokinetic Studies ◽

Gram Negative ◽

Carbapenem Resistant ◽

Median Daily Dose

Population pharmacokinetic studies have suggested that high polymyxin B (PMB) doses (≥30,000 IU/kg/day) can improve bacterial kill in carbapenem-resistant Gram-negative bacteria (CR-GNB). We aim to describe the efficacy and nephrotoxicity of patients with CR-GNB infections prescribed high-dose PMB. A single-centre cohort study was conducted from 2013 to 2016 on septic patients with CR-GNB infection and prescribed high-dose PMB (~30,000 IU/kg/day) for ≥72 h. Study outcomes included 30-day mortality and acute kidney injury (AKI) development. Factors associated with AKI were identified using multivariable regression. Forty-three patients with 58 CR-GNB received high-dose PMB; 57/58 (98.3%) CR-GNB were susceptible to PMB. The median daily dose and duration of high-dose PMB were 32,051 IU/kg/day (IQR, 29,340–34,884 IU/kg/day) and 14 days (IQR, 7–28 days), respectively. Thirty-day mortality was observed in 7 (16.3%) patients. AKI was observed in 25 (58.1%) patients with a median onset of 8 days (IQR, 6–13 days). Higher daily PMB dose (aOR,1.01; 95% CI, 1.00–1.02) and higher number of concurrent nephrotoxins (aOR, 2.14; 95% CI; 1.03–4.45) were independently associated with AKI. We observed that a sizable proportion developed AKI in CR-GNB patients described high-dose PMB; hence, the potential benefits must be weighed against increased AKI risk. Concurrent nephrotoxins should be avoided to reduce nephrotoxicity.

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Comparison of continuous versus intermittent intravenous infusion of colistimethate sodium (colistin) for treatment of carbapenem-resistant Gram-negative bacterial infections

10.26226/morressier.56d6be79d462b80296c97bf3 ◽

2016 ◽

Author(s):

Jennifer Curello

Keyword(s):

Intravenous Infusion ◽

Bacterial Infections ◽

Gram Negative ◽

Carbapenem Resistant ◽

Colistimethate Sodium

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The Search for a Practical Method for Colistin Susceptibility Testing: Have We Found It by Going Back to the Future?

Journal of Clinical Microbiology ◽

10.1128/jcm.01608-18 ◽

2018 ◽

Vol 57 (2) ◽

Cited By ~ 5

Author(s):

Michael J. Satlin

Keyword(s):

Escherichia Coli ◽

Bacterial Infections ◽

Clinical Microbiology ◽

Susceptibility Testing ◽

Practical Method ◽

Broth Microdilution ◽

Excellent Performance ◽

Gram Negative ◽

Content Type ◽

Carbapenem Resistant

ABSTRACTPolymyxins are relied upon for the treatment of carbapenem-resistant Gram-negative bacterial infections, but polymyxin resistance is increasing. Only broth microdilution is recommended for polymyxin susceptibility testing, but this method is impractical for most clinical microbiology laboratories. An article in this issue of theJournal of Clinical Microbiology(P. J. Simner, Y. Bergman, M. Trejo, A. A. Roberts, R. Marayan, T. Tekle, S. Campeau, A. Kazmi, D. Bell, S. Lewis, P. D. Tamma, R. Humphries, and J. A. Hindler, J Clin Microbiol 57:e01163-18, 2019,https://doi.org/10.1128/JCM.01163-18) found that colistin broth disk elution, a method that requires only colistin disks and broth, had excellent performance compared to broth microdilution for all strains exceptmcr-positiveEscherichia colistrains.

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