Antibiotics

Editorial

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5 pages, 188 KiB

Open AccessEditorial

Gram-Negative Bloodstream Infection: Implications of Antimicrobial Resistance on Clinical Outcomes and Therapy

by Majdi N. Al-Hasan

Antibiotics 2020, 9(12), 922; https://doi.org/10.3390/antibiotics9120922 - 18 Dec 2020

Cited by 4 | Viewed by 2627

Abstract

The age- and sex-adjusted incidence rate of Gram-negative bloodstream infection (GN-BSI) is 84 [...] Full article

(This article belongs to the Special Issue Gram-Negative Bloodstream Infections)

Research

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15 pages, 2371 KiB

Open AccessArticle

Iron Chelation in Murine Models of Systemic Inflammation Induced by Gram-Positive and Gram-Negative Toxins

by Danielle Fokam, Kayle Dickson, Kiyana Kamali, Bruce Holbein, Patricia Colp, Ashley Stueck, Juan Zhou and Christian Lehmann

Antibiotics 2020, 9(6), 283; https://doi.org/10.3390/antibiotics9060283 - 26 May 2020

Cited by 16 | Viewed by 3669

Abstract

Iron is an essential element for various physiological processes, but its levels must remain tightly regulated to avoid cellular damage. Similarly, iron plays a dual role in systemic inflammation, such as with sepsis. Leukocytes utilize iron to produce reactive oxygen species (ROS) to [...] Read more.

Iron is an essential element for various physiological processes, but its levels must remain tightly regulated to avoid cellular damage. Similarly, iron plays a dual role in systemic inflammation, such as with sepsis. Leukocytes utilize iron to produce reactive oxygen species (ROS) to kill bacteria, but pathologically increased iron-catalyzed ROS production in sepsis can lead to damage of host cells, multi-organ failure and death. Temporary reduction in bioavailable iron represents a potential therapeutic target in sepsis. This study investigates the effect of the novel iron chelator, DIBI, in murine models of systemic (hyper-)inflammation: C57BL/6 mice were challenged with toxins from Gram-positive (Staphylococcus aureus: lipoteichoic acid, peptidoglycan) and Gram-negative bacteria (Escherichia coli and Klebsiella pneumoniae: lipopolysaccharide). Intravital microscopy (IVM) was performed to assess immune cell activation and its impact on microvascular blood flow in vivo in the microcirculation of the gut. Plasma inflammatory mediators were measured via multiplex assay, and morphologic change in intestinal tissue was evaluated. DIBI treatment decreased leukocyte (hyper-)activation induced by Gram-positive and Gram-negative toxins. In some cases, it preserved capillary perfusion, reduced plasma inflammatory markers and attenuated tissue damage. These findings support the utility of DIBI as a novel treatment for systemic inflammation, e.g., sepsis. Full article

(This article belongs to the Special Issue Gram-Negative Bloodstream Infections)

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15 pages, 1750 KiB

Open AccessArticle

Molecular Typing, Characterization of Antimicrobial Resistance, Virulence Profiling and Analysis of Whole-Genome Sequence of Clinical Klebsiella pneumoniae Isolates

by Andrey Shelenkov, Yulia Mikhaylova, Yuri Yanushevich, Andrei Samoilov, Lyudmila Petrova, Valeria Fomina, Vitaly Gusarov, Mikhail Zamyatin, Dmitriy Shagin and Vasiliy Akimkin

Antibiotics 2020, 9(5), 261; https://doi.org/10.3390/antibiotics9050261 - 17 May 2020

Cited by 36 | Viewed by 5225

Abstract

Klebsiella pneumoniae is one of the most important pathogens concerned with multidrug resistance in healthcare-associated infections. The treating of infections caused by this bacterium is complicated due to the emergence and rapid spreading of carbapenem-resistant strains, which are associated with high mortality rates. [...] Read more.

Klebsiella pneumoniae is one of the most important pathogens concerned with multidrug resistance in healthcare-associated infections. The treating of infections caused by this bacterium is complicated due to the emergence and rapid spreading of carbapenem-resistant strains, which are associated with high mortality rates. Recently, several hypervirulent and carbapenemase-producing isolates were reported that make the situation even more complicated. In order to better understand the resistance and virulence mechanisms, and, in turn, to develop effective treatment strategies for the infections caused by multidrug-resistant K. pneumoniae, more comprehensive genomic and phenotypic data are required. Here, we present the first detailed molecular epidemiology report based on second and third generation (long-read) sequencing for the clinical isolates of K. pneumoniae in the Russian Federation. The data include three schemes of molecular typing, phenotypic and genotypic antibiotic resistance determination, as well as the virulence and plasmid profiling for 36 K. pneumoniae isolates. We have revealed 2 new multilocus sequence typing (MLST)-based sequence types, 32 multidrug-resistant (MDR) isolates and 5 colistin-resistant isolates in our samples. Three MDR isolates belonged to a very rare ST377 type. The whole genome sequences and additional data obtained will greatly facilitate further investigations in the field of antimicrobial resistance studies. Full article

(This article belongs to the Special Issue Gram-Negative Bloodstream Infections)

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13 pages, 559 KiB

Open AccessArticle

Multicenter, Observational Cohort Study Evaluating Third-Generation Cephalosporin Therapy for Bloodstream Infections Secondary to Enterobacter, Serratia, and Citrobacter Species

by Caroline Derrick, P. Brandon Bookstaver, Zhiqiang K. Lu, Christopher M. Bland, S. Travis King, Kayla R. Stover, Kathey Rumley, Shawn H. MacVane, Jenna Swindler, Scott Kincaid, Trisha Branan, David Cluck, Benjamin Britt, Kelly E. Pillinger, Bruce M. Jones, Virginia Fleming, V. Paul DiMondi, Sandy Estrada, Brad Crane, Brian Odle, Majdi N. Al-Hasan and Julie Ann Justo Show full author list Hide full author list

Antibiotics 2020, 9(5), 254; https://doi.org/10.3390/antibiotics9050254 - 14 May 2020

Cited by 16 | Viewed by 7235

Abstract

Objectives: There is debate on whether the use of third-generation cephalosporins (3GC) increases the risk of clinical failure in bloodstream infections (BSIs) caused by chromosomally-mediated AmpC-producing Enterobacterales (CAE). This study evaluates the impact of definitive 3GC therapy versus other antibiotics on clinical outcomes [...] Read more.

Objectives: There is debate on whether the use of third-generation cephalosporins (3GC) increases the risk of clinical failure in bloodstream infections (BSIs) caused by chromosomally-mediated AmpC-producing Enterobacterales (CAE). This study evaluates the impact of definitive 3GC therapy versus other antibiotics on clinical outcomes in BSIs due to Enterobacter, Serratia, or Citrobacter species. Methods: This multicenter, retrospective cohort study evaluated adult hospitalized patients with BSIs secondary to Enterobacter, Serratia, or Citrobacter species from 1 January 2006 to 1 September 2014. Definitive 3GC therapy was compared to definitive therapy with other non-3GC antibiotics. Multivariable Cox proportional hazards regression evaluated the impact of definitive 3GC on overall treatment failure (OTF) as a composite of in-hospital mortality, 30-day hospital readmission, or 90-day reinfection. Results: A total of 381 patients from 18 institutions in the southeastern United States were enrolled. Common sources of BSIs were the urinary tract and central venous catheters (78 (20.5%) patients each). Definitive 3GC therapy was utilized in 65 (17.1%) patients. OTF occurred in 22/65 patients (33.9%) in the definitive 3GC group vs. 94/316 (29.8%) in the non-3GC group (p = 0.51). Individual components of OTF were comparable between groups. Risk of OTF was comparable with definitive 3GC therapy vs. definitive non-3GC therapy (aHR 0.93, 95% CI 0.51–1.72) in multivariable Cox proportional hazards regression analysis. Conclusions: These outcomes suggest definitive 3GC therapy does not significantly alter the risk of poor clinical outcomes in the treatment of BSIs secondary to Enterobacter, Serratia, or Citrobacter species compared to other antimicrobial agents. Full article

(This article belongs to the Special Issue Gram-Negative Bloodstream Infections)

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8 pages, 1104 KiB

Open AccessArticle

Impact of Reappraisal of Fluoroquinolone Minimum Inhibitory Concentration Susceptibility Breakpoints in Gram-Negative Bloodstream Isolates

by Stephanie C. Shealy, Matthew M. Brigmon, Julie Ann Justo, P. Brandon Bookstaver, Joseph Kohn and Majdi N. Al-Hasan

Antibiotics 2020, 9(4), 189; https://doi.org/10.3390/antibiotics9040189 - 17 Apr 2020

Cited by 5 | Viewed by 4235

Abstract

The Clinical Laboratory Standards Institute lowered the fluoroquinolone minimum inhibitory concentration (MIC) susceptibility breakpoints for Enterobacteriaceae and glucose non-fermenting Gram-negative bacilli in January 2019. This retrospective cohort study describes the impact of this reappraisal on ciprofloxacin susceptibility overall and in patients with risk [...] Read more.

The Clinical Laboratory Standards Institute lowered the fluoroquinolone minimum inhibitory concentration (MIC) susceptibility breakpoints for Enterobacteriaceae and glucose non-fermenting Gram-negative bacilli in January 2019. This retrospective cohort study describes the impact of this reappraisal on ciprofloxacin susceptibility overall and in patients with risk factors for antimicrobial resistance. Gram-negative bloodstream isolates collected from hospitalized adults at Prisma Health-Midlands hospitals in South Carolina, USA, from January 2010 to December 2014 were included. Matched pairs mean difference (MD) with 95% confidence intervals (CI) were calculated to examine the change in ciprofloxacin susceptibility after MIC breakpoint reappraisal. Susceptibility of Enterobacteriaceae to ciprofloxacin declined by 5.2% (95% CI: −6.6, −3.8; p < 0.001) after reappraisal. The largest impact was demonstrated among Pseudomonas aeruginosa bloodstream isolates (MD −7.8, 95% CI: −14.6, −1.1; p = 0.02) despite more conservative revision in ciprofloxacin MIC breakpoints. Among antimicrobial resistance risk factors, fluoroquinolone exposure within the previous 90 days was associated with the largest change in ciprofloxacin susceptibility (MD −9.3, 95% CI: −16.1, −2.6; p = 0.007). Reappraisal of fluoroquinolone MIC breakpoints has a variable impact on the susceptibility of bloodstream isolates by microbiology and patient population. Healthcare systems should be vigilant to systematically adopt this updated recommendation in order to optimize antimicrobial therapy in patients with bloodstream and other serious infections. Full article

(This article belongs to the Special Issue Gram-Negative Bloodstream Infections)

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10 pages, 615 KiB

Open AccessArticle

Excess Length of Acute Inpatient Stay Attributable to Acquisition of Hospital-Onset Gram-Negative Bloodstream Infection with and without Antibiotic Resistance: A Multistate Model Analysis

by Hiroyuki Suzuki, Eli N Perencevich, Rajeshwari Nair, Daniel J Livorsi and Michihiko Goto

Antibiotics 2020, 9(2), 96; https://doi.org/10.3390/antibiotics9020096 - 23 Feb 2020

Cited by 11 | Viewed by 3539

Abstract

Excess length of stay (LOS) is an important outcome when assessing the burden of nosocomial infection, but it can be subject to survival bias. We aimed to estimate the change in LOS attributable to hospital-onset (HO) Escherichia coli/Klebsiella spp. bacteremia using [...] Read more.

Excess length of stay (LOS) is an important outcome when assessing the burden of nosocomial infection, but it can be subject to survival bias. We aimed to estimate the change in LOS attributable to hospital-onset (HO) Escherichia coli/Klebsiella spp. bacteremia using multistate models to circumvent survival bias. We analyzed a cohort of all patients with HO E. coli/Klebsiella spp. bacteremia and matched uninfected control patients within the U.S. Veterans Health Administration System in 2003–2013. A multistate model was used to estimate the change in LOS as an effect of the intermediate state (HO-bacteremia). We stratified analyses by susceptibilities to fluoroquinolones (fluoroquinolone susceptible (FQ-S)/fluoroquinolone resistant (FQ-R)) and extended-spectrum cephalosporins (ESC susceptible (ESC-S)/ESC resistant (ESC-R)). Among the 5964 patients with HO bacteremia analyzed, 957 (16.9%) and 1638 (28.9%) patients had organisms resistant to FQ and ESC, respectively. Any HO E.coli/Klebsiella bacteremia was associated with excess LOS, and both FQ-R and ESC-R were associated with a longer LOS than susceptible strains, but the additional burdens attributable to resistance were small compared to HO bacteremia itself (FQ-S: 12.13 days vs. FQ-R: 12.94 days, difference: 0.81 days (95% CI: 0.56–1.05), p < 0.001 and ESC-S: 11.57 days vs. ESC-R: 16.56 days, difference: 4.99 days (95% CI: 4.75–5.24), p < 0.001). Accurate measurements of excess attributable LOS associated with resistance can help support the business case for infection control interventions. Full article

(This article belongs to the Special Issue Gram-Negative Bloodstream Infections)

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11 pages, 892 KiB

Open AccessArticle

Definitive Cefazolin Treatment for Community-Onset Enterobacteriaceae Bacteremia Based on the Contemporary CLSI Breakpoint: Clinical Experience of a Medical Center in Southern Taiwan

by Ching-Chi Lee, Chung-Hsun Lee, Po-Lin Chen, Chih-Chia Hsieh, Hung-Jen Tang and Wen-Chien Ko

Antibiotics 2019, 8(4), 216; https://doi.org/10.3390/antibiotics8040216 - 10 Nov 2019

Cited by 5 | Viewed by 4741

Abstract

Cefazolin is traditionally active against Escherichia coli, Klebsiella species, and Proteus mirabilis (EKP) isolates. The Clinical and Laboratory Standards Institute (CLSI) has twice updated cefazolin susceptibility breakpoints for EKP since 2010, but its role in the definitive treatment of cefazolin-susceptible EKP bacteremia remains [...] Read more.

Cefazolin is traditionally active against Escherichia coli, Klebsiella species, and Proteus mirabilis (EKP) isolates. The Clinical and Laboratory Standards Institute (CLSI) has twice updated cefazolin susceptibility breakpoints for EKP since 2010, but its role in the definitive treatment of cefazolin-susceptible EKP bacteremia remains debated. To assess its efficacy as a definitive agent, the 8-year cohort study consisted of 941 adults with monomicrobial cefazolin-susceptible EKP bacteremia, based on the CLSI criteria issued in 2019, was retrospectively established in a medical center. Based on the definitive antimicrobial prescription, eligible patients were categorized into the cefazolin (399 patients, 42.4%) and broader-spectrum antibiotic (BSA) (542, 57.6%) groups. Initially, fewer proportions of patients with fatal comorbidities (the McCabe classification) and the critical illness (a Pitt bacteremia score ≥4) at the onset and day 3 of the bacteremia episode were found in the cefazolin group, compared to the BSA group. After propensity-score matching, no significant difference of patient proportions between the cefazolin (345 patients) and BSA (345) groups was observed, in terms of the elderly, types and severity of comorbidities, bacteremia severity at the onset and day 3, major bacteremia sources, and the 15-day and 30-day crude mortality. In early outcomes, lengths of time to defervescence, intravenous (IV) antimicrobial administration, and hospitalization were similar in the two matched groups; lower costs of IV antimicrobial administration were observed in the cefazolin group. Notably, for late outcomes, lower proportions of post-treatment infections caused by antimicrobial-resistant pathogens (ARPs) and post-treatment mortality rates were evidenced in the cefazolin group. Conclusively, cefazolin is definitively efficacious and cost-effective for adults with community-onset cefazolin-susceptible EKP bacteremia in this one-center study, compared to BSAs. However, a prospective multicenter study should be conducted for external validation with other communities. Full article

(This article belongs to the Special Issue Gram-Negative Bloodstream Infections)

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Review

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18 pages, 596 KiB

Open AccessReview

Treatment of Bloodstream Infections Due to Gram-Negative Bacteria with Difficult-to-Treat Resistance

by Matteo Bassetti, Antonio Vena, Chiara Sepulcri, Daniele Roberto Giacobbe and Maddalena Peghin

Antibiotics 2020, 9(9), 632; https://doi.org/10.3390/antibiotics9090632 - 22 Sep 2020

Cited by 50 | Viewed by 7400

Abstract

The rising incidence of bloodstream infections (BSI) due to Gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) has been recognized as a global emergency. The aim of this review is to provide a comprehensive assessment of the mechanisms of antibiotic resistance, epidemiology and treatment [...] Read more.

The rising incidence of bloodstream infections (BSI) due to Gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) has been recognized as a global emergency. The aim of this review is to provide a comprehensive assessment of the mechanisms of antibiotic resistance, epidemiology and treatment options for BSI caused by GNB with DTR, namely extended-spectrum Beta-lactamase-producing Enterobacteriales; carbapenem-resistant Enterobacteriales; DTR Pseudomonas aeruginosa; and DTR Acinetobacter baumannii. Full article

(This article belongs to the Special Issue Gram-Negative Bloodstream Infections)

9 pages, 226 KiB

Open AccessReview

Current Concepts in Community and Ventilator Associated Lower Respiratory Tract Infections in ICU Patients

by Ignacio Martin-Loeches

Antibiotics 2020, 9(7), 380; https://doi.org/10.3390/antibiotics9070380 - 5 Jul 2020

Cited by 6 | Viewed by 3349

Abstract

It is widely known that pneumonia (either community acquired or hospital acquired, as like ventilator associated pneumonia (VAP)), is the most frequent type of severe infection and continues to pose a significant burden on healthcare services worldwide. Despite new diagnostic developments, most pneumonia [...] Read more.

It is widely known that pneumonia (either community acquired or hospital acquired, as like ventilator associated pneumonia (VAP)), is the most frequent type of severe infection and continues to pose a significant burden on healthcare services worldwide. Despite new diagnostic developments, most pneumonia cases continue to be difficult to diagnose clinically, partly due to acquired antibiotic resistance and the lack of a ‘gold standard’ method of diagnosis. In other words, the lack of a rapid, accurate diagnostic test, as well as the uncertainty of the initial etiologic diagnosis and the risk stratification, results in empirical antibiotic treatments. There are significant changes in the aetiology of patients with ventilator associated lower respiratory tract infections (VA-LRTI), which are characterised by a higher incidence of multi drug resistant organisms. Evidence suggests that when patients with VA-LRTI develop organ failure, the associated mortality can be exceptionally high with frequent complications, including acute respiratory distress syndrome, acute kidney injury, and septic shock. Appropriate antibiotic treatments must consider that the present cardiovascular failure seen in patients has a different association with the patient’s mortality. Unlike patients with less severe clinical presentations, who have a higher chance of survival when the appropriate antibiotics are administered promptly, for patients with a severe subtype of the disease, the appropriateness of antibiotic treatment will impact the patient’s outcome to a lesser extent. The present review highlights certain factors detectable at the time of admission that could indicate patients who are at a high risk of bacteraemia and who, therefore, merit more intense therapy and stratified care. Full article

(This article belongs to the Special Issue Gram-Negative Bloodstream Infections)

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