scholarly journals Insights into the clinical management of carbapenem-resistant Gram-negative infections: An Italian retrospective clinical chart review

2020 ◽  
Vol 12 (2) ◽  
Author(s):  
Guido Granata ◽  
Davide Manissero ◽  
Maria Vittoria Oppia ◽  
Keiko Tone ◽  
Bin Cai ◽  
...  
Keyword(s):  
Chart Review ◽  
Respiratory Infections ◽  
Health Care Facilities ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Medical Chart Review ◽  
Duration Of Hospitalization ◽  
History Of ◽  
Tract Infections ◽  
Clinical Chart

There is a lack of consensus regarding management of infections with carbapenem- resistant Gram-negative (CR-GN) pathogens. This study comprised a medical chart review to assess patient management in a high CR prevalence setting. Data was collated retrospectively from medical records of patients hospitalized between November 1st, 2015 and October 31st, 2016. Of 29 patients, 66% had respiratory tract infections. Median duration of hospitalization was 28 days and ~50% of patients were admitted to the intensive care unit, with 77% remaining for >2 weeks. Median time to obtain respiratory culture results was 5 days. Isolation of patients with diagnosed CR-GN infection took ≥5 days in >50% of patients. A majority (76%) of patients received ≥1 antibiotic before providing a specimen for culture; a total of 17 antibiotic treatments were used. Overall, 72% of patients, and 68% of those with respiratory infections, were discharged alive; 38% were discharged without further antibiotics. The difficulties in achieving effective management in patients with CR-GN infections are largely due to complex co-morbidities, a history of prior antibiotic treatment, and multiple referrals across health care facilities.

scholarly journals Διερεύνηση νέων β-λακταμασών σε στελέχη gram-αρνητικών βακτηρίων στην κοινότητα

2011 ◽  
Author(s):  
Αγγελική Πούλου
Keyword(s):  
Urinary Tract ◽  
Urinary Tract Infections ◽  
Health Care Facilities ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Plasmid Analysis ◽  
Previous Hospitalization ◽  
Tract Infections ◽  
Community Onset

The aim of the study was to investigate the dissemination in the community of carbapenem-resistant gram-negative bacteria and the mechanisms of acquired resistance.Patients who were referred to the outpatient department of Serres General Hospital with community-onset infections due to carbapenem-resistant gram-negative bacteria during a 3 year period (2005-2008) were included in this study. The selected isolates were tested by determination of agar dilution MICs, phenotypic carbapenemase testing and molecular typing methods. PCR and sequencing analyses were employed for identification of bla genes and mapping of the integron carrying the metallo-β-lactamase (MBL) gene. The location of the MBL allele was investigated by mating experiments, plasmid analysis, and hybridization of the Southern-blotted plasmid extract with a blaVIM probe. The demographic and clinical characteristics of the outpatients were prospectively collected.During the study period 12 Proteus mirabilis, 97 Pseudomonas aeruginosa and 24 Klebsiella pneumoniae isolates with reduced susceptibility to imipenem and/or meropenem were recovered from urinary tract infections of 12, 45 and 12 outpatients, respectively. As many as 64 of the outpatients had a history of previous hospitalization or visit to the healthcare facilities in the preceding year while the remaining 5 outpatients with urinary tract infections due to P. aeruginosa carbapenem-resistant isolates had not been hospital admission in the preceding year.In 18 outpatients infected with P. aeruginosa and 6 outpatients infected with K. pneumoniae the carbapenem-resistant organisms caused recurrent community-onset infections, while in three outpatients P. aeruginosa isolates were also implicated in community-onset bacteremic episodes. Diabetes mellitus, prostatic hyperplasia and infection with an MBL-producing strain during a previous hospitalization were significantly associated with recurrent infections in the community setting.Recurrent infections were not detected among patients infected with MBL-producing P. mirabilis isolates. Among P. mirabilis isolates imipenem, meropenem and ertapenem MICs ranged from 32 to >128 mg/L, 1 to 8 mg/L and 0.5 to 4 mg/L, respectively. The isolates originated from the same clonal strain and harbored a blaVIM-1 gene in a common integron structure. Conjugation experiments, plasmid analysis and hybridization assays indicated the chromosomal location of blaVIM-1 gene. All 45 single-patient P. aeruginosa isolates harbored the blaVIM-2 MBL gene in a common class 1 integron structure. They belonged to one predominant pulsed-field gel electrophoresis type and three sporadically detected types; two of the sporadic clonal types were identified among outpatients without previous exposure to health care facilities, while the predominant clonal type was also identified to cause infections in hospitalized patient. The integron carrying the MBL gene was located on the bacterial chromosome.For the K. pneumoniae isolates imipenem, meropenem and ertapenem MICs ranged from 8 to 64mg/L, 4 to 32mg/L and 8 to 128mg/L, respectively. All studied isolates as well as those two recovered during previous hospitalization belonged to a single PFGE clone. They harbored a plasmid-mediated blaVIM-1 gene in an integron structure that has been previously described among clinical isolates from Greek hospitals.This is the first study to document the dissemination of MBL-producing P. mirabilis, P. aeruginosa and K. pneumoniae isolates in the community. Present clinical and molecular data provided evidence that MBL-producing strains could easily disseminated in the community from patients colonized during a previous hospitalization. Increased awareness and intensified infection control practices in the hospital as well as the community setting are the keys to curtailing the spread of these alarming carbapenem resistant pathogens.

scholarly journals Antimicrobial Activity of Ceftolozane–Tazobactam Tested against Contemporary (2012–2016) Enterobacteriaceae and Pseudomonas aeruginosa Isolates by US Census Division

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S371-S372
Author(s):  
Dee Shortridge ◽  
Leonard R Duncan ◽  
Michael A Pfaller ◽  
Robert K Flamm
Keyword(s):  
Pseudomonas Aeruginosa ◽  
The United States ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Tract Infections ◽  
Abdominal Infections ◽  
Us Census ◽  
Phenotype Screen ◽  
Lactamase Inhibitor ◽  
Research Grant

Abstract Background Ceftolozane-tazobactam (C-T) is a combination of a novel antipseudomonal cephalosporin and a well-described β-lactamase inhibitor. C-T was approved by the United States (US) Food and Drug Administration in 2014 for complicated urinary tract infections, including acute pyelonephritis and complicated intra-abdominal infections. C-T is currently in clinical trials for the treatment of nosocomial pneumonia. The Program to Assess Ceftolozane-Tazobactam Susceptibility (PACTS) monitors C-T resistance to gram-negative (GN) isolates worldwide. In this study, the activities of C-T and comparators vs. GN isolates from each of the 9 US Census divisions were compared. Methods A total of 18,856 Enterobacteriaceae (ENT) and 4,735 Pseudomonas aeruginosa (PSA) isolates were collected from 32 US hospitals in 2012–2016. Isolates were tested for susceptibility (S) to C-T and comparators by CLSI broth microdilution methodology in a central monitoring laboratory. Other antibiotics tested included amikacin (AMK), ceftazidime (CAZ), colistin (COL), meropenem (MER), and piperacillin-tazobactam (TZP). The following resistant phenotypes were analyzed for ENT: carbapenem resistant (CRE); extended-spectrum β-lactamase phenotype screen-positive (ESBL); and ESBL, nonCRE. or PSA, MER-nonsusceptible (NS), TZP-NS, and CAZ-NS isolates were analyzed. CLSI (2017) interpretive criteria were used. Results For all ENT, 94.2% were S to C-T, 91.5% were S to TZP, 98.0% were S to MER, and 98.8% were S to AMK; 1,697 (9.0%) were ESBL, nonCRE and 356 (1.9%) were CRE. For all PSA isolates, 97.4% were S to C-T, 99.3% were S to COL, 96.9% were S to AMK, and 81.2% were S to MER. The % C-T S for each division (DIV) are shown in the table. The % C-T S for ENT ranged from 98.1% (DIV 4) to 87.4% (DIV 2) and % C-T S for ESBL, nonCRE ranged from 93.8% in DIV 4 to 79.8% in DIV 7. For PSA, the % C-T S ranged from 99.6% in DIV 4 to 94.9% in DIV 9. Activity of C-T against PSA NS to MER, CAZ or TZP varied by division and was >80% for all except DIV 9. Conclusion Against PSA, only COL was more active than C-T. C-T demonstrated potent activity against PSA NS to other β-lactams. For ENT, overall activity was good. For both PSA and ENT, C-T varied by DIV. Disclosures D. Shortridge, Merck: Research Contractor, Research grant; L. R. Duncan, Merck: Research Contractor, Research grant; M. A. Pfaller, Merck: Research Contractor, Research grant; R. K. Flamm, Merck: Research Contractor, Research grant

scholarly journals Clinical management of cUTI, cIAI, and HABP/VABP attributable to carbapenem-resistant Gram-negative infections in Spain

2021 ◽  
Author(s):  
Ricard Ferrer ◽  
María Carmen Fariñas ◽  
Emilio Maseda ◽  
Miguel Salavert ◽  
German Bou ◽  
...  
Keyword(s):  
Clinical Management ◽  
Bacterial Pneumonia ◽  
Chart Review ◽  
Complicated Urinary Tract Infection ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
Post Discharge ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Healthcare Associated

Introduction. Carbapenem-resistant Gram-negative (CRGN) infections are a major public health problem in Spain, often implicated in complicated, healthcare-associated infections that require the use of potentially toxic antibacterial agents of last resort. The objective of this study was to assess the clinical management of complicated infections caused by CRGN bacteria in Spanish hospitals. Methods. The study included: 1) a survey assessing the GN infection and antibacterial susceptibility profile in five participating Spanish hospitals and 2) a non-interventional, retrospective single cohort chart review of 100 patients with complicated urinary tract infection (cUTI), complicated intra-abdominal infection (cIAI), or hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia (HABP/VABP) attributable to CRGN pathogens. Results. In the participating hospitals CRGN prevalence was 9.3% amongst complicated infections. In the retrospective cohort, 92% of infections were healthcare-associated, and Klebsiella pneumoniae and Pseudomonas aeruginosa were the most common pathogens. OXA was the most frequently detected carbapenemase type (71.4%). We found that carbapenems were frequently used to treat cUTI, cIAI, HABP/VABP caused by CRGN pathogens. Carbapenem use, particularly in combination with other agents, persisted after confirmation of carbapenem resistance. Clinical cure was 66.0%, mortality during hospitalization 35.0%, mortality at the time of chart review 62.0%, and 6-months-post-discharge readmission 47.7%. Conclusion. Our results reflect the high burden and unmet needs associated with the management of complicated infections attributable to CRGN pathogens in Spain and highlight the urgent need for enhanced clinical management of these difficult-to-treat infections.

Cefiderocol: A Siderophore Cephalosporin

2020 ◽  
Vol 54 (12) ◽  
pp. 1215-1231
Author(s):  
Rania M. El-Lababidi ◽  
John George Rizk
Keyword(s):  
Nosocomial Pneumonia ◽  
Data Extraction ◽  
Multidrug Resistant ◽  
Phase Iii ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Study Selection ◽  
Serious Infections ◽  
Wide Range ◽  
Tract Infections

Objective: This article reviews the available data on the chemistry, spectrum of activity, pharmacokinetic and pharmacodynamic properties, clinical efficacy, and potential place in therapy of cefiderocol. Data Sources: A literature search through PubMed, Google Scholar, and ClinicalTrials.gov was conducted (2009 to March 2020) using the search terms cefiderocol and S-649266. Abstracts presented at recent conferences, prescribing information, and information from the US Food and Drug Administration (FDA) and the manufacturer’s website were reviewed. Study Selection and Data Extraction: All relevant published articles, package inserts, and unpublished meeting abstracts on cefiderocol were reviewed. Data Synthesis: Cefiderocol is the first siderophore antibiotic to be approved by the FDA. It was shown to be active against a wide range of resistant Gram-negative pathogens, including multidrug-resistant (MDR) Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacteriaceae, and Stenotrophomonas maltophilia. Cefiderocol was studied in the treatment of adult patients with complicated urinary tract infections (cUTIs) and nosocomial pneumonia and was well tolerated. In a recently completed prospective study, higher mortality was observed with cefiderocol in the treatment of serious infections caused by carbapenem-resistant (CR) Gram-negative pathogens. Relevance to Patient Care and Clinical Practice: The approval of cefiderocol provides a new option in the treatment of cUTIs and potentially treatment of nosocomial pneumonia caused by resistant Gram-negative pathogens. Given the higher mortality observed with cefiderocol, its use in the treatment of CR Gram-negative infections should be carefully considered. Conclusion: Cefiderocol shows promising activity against MDR Gram-negative pathogens. Its use in the treatment of serious infections caused by CR Gram-negative bacteria needs further evaluation in phase III clinical studies.

scholarly journals In Vitro Activity of Cefiderocol Against a Broad Range of Clinically Important Gram-negative Bacteria

2019 ◽  
Vol 69 (Supplement_7) ◽  
pp. S544-S551 ◽  
Author(s):  
Yoshinori Yamano
Keyword(s):  
Efflux Pump ◽  
Bloodstream Infections ◽  
Resistance Mechanisms ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Highly Active ◽  
Carbapenem Resistant ◽  
Surveillance Programs ◽  
Tract Infections

AbstractCarbapenem-resistant gram-negative bacteria including Enterobacteriaceae as well as nonfermenters, such as Pseudomonas aeruginosa and Acinetobacter baumannii, have emerged as significant global clinical threats. Although new agents have recently been approved, none are active across the entire range of resistance mechanisms presented by carbapenem-resistant gram-negative bacteria. Cefiderocol, a novel siderophore cephalosporin, has been shown in large surveillance programs and independent in vitro studies to be highly active against all key gram-negative causative pathogens isolated from patients with hospital-acquired or ventilator-associated pneumonia, bloodstream infections, or complicated urinary tract infections. The improved structure, the novel mode of entry into bacteria, and its stability against carbapenemases enables cefiderocol to exhibit high potency against isolates that produce carbapenemases of all classes or are resistant due to porin channel mutations and/or efflux pump overexpression. Resistance to cefiderocol is uncommon and appears to be multifactorial.

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

2020 ◽  
Vol 7 (6) ◽  
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.

Cefiderocol: A new cephalosporin stratagem against multidrug resistant gram-negative bacteria

2021 ◽  
Author(s):  
Sharon Ong’uti ◽  
Mary Czech ◽  
Elizabeth Robilotti ◽  
Marisa Holubar
Keyword(s):  
Clinical Trials ◽  
Multidrug Resistant ◽  
Cell Entry ◽  
Phase Iii ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Phase Iii Clinical Trials ◽  
Carbapenem Resistant ◽  
Tract Infections

Abstract Cefiderocol is a novel injectable siderophore cephalosporin which hijacks the bacterial iron transport machinery to facilitate cell entry and achieve high periplasmic concentrations. It has broad in vitro activity against gram-negative bacteria, including multidrug resistant (MDR) organisms like carbapenem resistant Enterobacterales (CRE), carbapenem resistant Pseudomonas aeruginosa and Acinetobacter baumannii. It was approved by the Food and Drug Administration (FDA) for the treatment of complicated urinary tract infections and nosocomial pneumonia based on clinical trials demonstrating noninferiority to comparators. In this review, we summarize the available in vitro and clinical data, including recent evidence from 2 phase III clinical trials (APEKS-NP and CREDIBLE-CR), and discuss the place of cefiderocol in the clinician’s armamentarium against MDR gram-negative infections.

scholarly journals 165. Cefiderocol Treatment for Serious Infections Caused by Carbapenem-resistant Bacteria: Post-hoc Analysis of Outcomes by Pathogen in the CREDIBLE-CR Study

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S212-S212
Author(s):  
Yuko Matsunaga ◽  
Mari Ariyasu ◽  
Miki Takemura ◽  
Yoshinori Yamano ◽  
Kiichiro Toyoizumi ◽  
...  
Keyword(s):  
Clinical Cure ◽  
Carbapenem Resistance ◽  
Bloodstream Infections ◽  
Resistant Bacteria ◽  
Open Label ◽  
Gram Negative ◽  
Mitt Population ◽  
Carbapenem Resistant ◽  
Serious Infections ◽  
Tract Infections

Abstract Background The efficacy and safety of cefiderocol (CFDC), a novel siderophore cephalosporin, for the treatment of serious infections due to carbapenem-resistant (CR) Gram-negative pathogens was assessed in the CREDIBLE-CR study. The current analysis evaluated clinical and microbiological outcomes by baseline CR pathogen. Methods An open-label, prospective, randomised 2:1, Phase 3 study (CREDIBLE-CR; NCT02714595) was conducted in adult patients with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia, bloodstream infections or sepsis, and complicated urinary tract infections caused by CR Gram-negative pathogens. Patients received either intravenous (IV) CFDC 2g, q8h, 3-h infusion, or IV best available therapy (BAT: up to 3 drugs in combination), for 7–14 days (extendable to 21 days). Clinical and microbiological outcomes were assessed in the CR microbiological intent-to-treat (CR-MITT) population by CR pathogen, baseline MIC and by mechanism of carbapenem resistance at test of cure (TOC). Only summary statistics were collected. Results In the CR-MITT population (CFDC N=80; BAT N=38), Acinetobacter baumannii (46.3% and 44.7%), Klebsiella pneumoniae (33.8% and 31.5%), and Pseudomonas aeruginosa (15% and 26%) were the most frequent pathogens in CFDC and BAT arms, respectively. For all CR pathogens, clinical cure rates were achieved in 52.5% in the CFDC arm and 50.0% in the BAT arm at TOC; rates were similar between treatment arms by baseline CR pathogen (Table 1). Numerically higher clinical cure and microbiological outcomes were observed with CFDC for Enterobacterales (Table 1), especially against NDM-producing bacteria or those with porin-channel mutations (Table 1). CFDC MIC values ranged between ≤0.03 and 4 μg/mL, except for one pathogen (Table 2). Microbiological outcomes for CR A. baumannii, CR K. pneumoniae, and CR P. aeruginosa at TOC by baseline MICs of ≤4 μg/mL ranged between 0–40%, 0–100%, and 0–100%, respectively; at MIC ≤4 μg/mL, clinical and microbiological outcomes were equal (Table 2). Conclusion CFDC, via a novel mechanism of entry and its stability against β-lactamases, was effective against serious infections caused by CR pathogens with various resistance mechanisms or baseline MIC values. Disclosures Yuko Matsunaga, MD, Shionogi Inc. (Employee) Mari Ariyasu, BPharm, Shionogi & Co., Ltd. (Employee) Miki Takemura, MSc, Shionogi & Co., Ltd. (Employee) Yoshinori Yamano, PhD, Shionogi & Co., Ltd. (Employee) Kiichiro Toyoizumi, PhD, Shionogi & Co., Ltd. (Employee) Masahiro Kinoshita, MPharm, Shionogi & Co., Ltd. (Employee) Roger Echols, MD, Shionogi Inc. (Consultant) Tsutae Den Nagata, MD, Shionogi & Co., Ltd. (Employee)

scholarly journals Acute Respiratory Infection in Co-Infection Form of Bacteria and Virus, Human Bocavirus with Streptococcus pneumoniae: A Case Report

2020 ◽  
Vol 7 (3) ◽  
Author(s):  
Mehrdad Mohammadi
Keyword(s):  
Respiratory Infection ◽  
Respiratory Infections ◽  
Causative Organism ◽  
Human Bocavirus ◽  
Gastrointestinal Infections ◽  
Case Presentation ◽  
Microbiological Methods ◽  
Life Threatening ◽  
History Of ◽  
Tract Infections

Introduction: Human bocavirus (HBoV) belongs to the Parvoviridae family, which has been revealed to be associated with respiratory and gastrointestinal infections in children. There are many reports worldwide on respiratory infection or gastroenteritis caused by this virus. Case Presentation: In a twin case (a girl and a boy), we demonstrated that HBoV infection in combination with Streptococcus pneumonia as co-infection caused the death of a 14-month-old girl with a history of high fever and wheezing. A week later, her brother presented with almost the same symptoms, but only HBoV was found in a nasopharyngeal aspirate sample. Discussion: This case suggests that lower respiratory tract infections due to HBoV may cause severe and life-threatening diseases, resulting in death in combination with a bacterial infection, such as S. pneumonia. The study suggests replacing multiplex PCR as a fast and meticulous method instead of conventional and time-consuming microbiological methods for determining the causative organism for respiratory infections.

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