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Carbapenem Resistant Gram-Negative Pathogens—a Comprehensive Approach to Acinetobacter, Pseudomonas, Enterobacteriaceae,...
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Carbapenem Resistant Gram-Negative Pathogens—a Comprehensive Approach to Acinetobacter, Pseudomonas, Enterobacteriaceae, and Stenotrophomonas: A Global Healthcare Threat

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotic Therapy in Infectious Diseases".

Deadline for manuscript submissions: closed (15 July 2024) | Viewed by 10121

Special Issue Editors

Dr. Darren W. Wong

E-Mail Website
Guest Editor
Associate Professor of Medicine, Division of Infectious Diseases, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA
Interests: multi-drug resistant gram-negative pathogens; complicated orthopedic infections and limb salvage; C. difficile disease; antibiotic stewardship and the integration of molecular diagnostics
Dr. Paul F. Riska

E-Mail Website
Guest Editor
Associate Professor of Medicine, Division of Infectious Diseases, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA
Interests: Clostridium difficile; tuberculosis; molecular epidemiology; molecular mechanisms of antibiotic resistance; bacteriophage therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Carbapenem-resistant bacteria are recognized as a major global healthcare threat. The World Health Organization’s (WHO) published list of ‘priority pathogens’ highlights carbapenem-resistance in Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae as three critical priority level 1 threats. These pathogens, along with Stenotrophomonas maltophilia, are a challenge for physicians with respect to establishing a timely diagnosis and an even greater challenge in determining an optimal treatment strategy. This Special Issue seeks to provide a comprehensive framework in all aspects of epidemiology, the integration of antibiotic stewardship and rapid diagnostics, and therapeutic approaches for these carbapenem-resistant bacterial pathogens. Research focused on the efficacy and utilization of novel treatment strategies and the integration of newly available therapeutic agents are of particular interest.

Dr. Darren W. Wong
Dr. Paul F. Riska
Guest Editors

Manuscript Submission Information

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Keywords

  • carbapenem resistance
  • CRE
  • Acinetobacter baumannii
  • Pseudomonas aeruginosa
  • KPC

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Published Papers (6 papers)

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Research

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11 pages, 269 KiB  
Article
Identification and Clinical Characteristics of Community-Acquired Acinetobacter baumannii in Patients Hospitalized for Moderate or Severe COVID-19 in Peru
by Wilmer Silva-Caso, Giancarlo Pérez-Lazo, Miguel Angel Aguilar-Luis, Adriana Morales-Moreno, José Ballena-López, Fernando Soto-Febres, Johanna Martins-Luna, Luis J. Del Valle, Sungmin Kym, Deysi Aguilar-Luis, Dayana Denegri-Hinostroza and Juana del Valle-Mendoza
Antibiotics 2024, 13(3), 266; https://doi.org/10.3390/antibiotics13030266 - 16 Mar 2024
Viewed by 2094
Abstract
Acinetobacter baumannii has been described as a cause of serious community-acquired infections in tropical countries. Currently, its implications when simultaneously identified with other pathogens are not yet adequately understood. A descriptive study was conducted on hospitalized patients with a diagnosis of moderate/severe SARS-CoV-2-induced [...] Read more.
Acinetobacter baumannii has been described as a cause of serious community-acquired infections in tropical countries. Currently, its implications when simultaneously identified with other pathogens are not yet adequately understood. A descriptive study was conducted on hospitalized patients with a diagnosis of moderate/severe SARS-CoV-2-induced pneumonia confirmed via real-time RT-PCR. Patients aged > 18 years who were admitted to a specialized COVID-19 treatment center in Peru were selected for enrollment. A. baumannii was detected via the PCR amplification of the blaOXA-51 gene obtained from nasopharyngeal swabs within 48 h of hospitalization. A total of 295 patients with COVID-19 who met the study inclusion criteria were enrolled. A. baumannii was simultaneously identified in 40/295 (13.5%) of COVID-19-hospitalized patients. Demographic data and comorbidities were comparable in both Acinetobacter-positive and -negative subgroups. However, patients identified as being infected with Acinetobacter were more likely to have received outpatient antibiotics prior to hospitalization, had a higher requirement for high-flow nasal cannula and a higher subjective incidence of fatigue, and were more likely to develop Acinetobacter-induced pneumonia during hospitalization. Conclusions: The group in which SARS-CoV-2 and A. baumannii were simultaneously identified had a higher proportion of fatigue, a higher frequency of requiring a high-flow cannula, and a higher proportion of superinfection with the same microorganism during hospitalization. Full article
(This article belongs to the Special Issue Carbapenem Resistant Gram-Negative Pathogens—a Comprehensive Approach to Acinetobacter, Pseudomonas, Enterobacteriaceae, and Stenotrophomonas: A Global Healthcare Threat)
21 pages, 918 KiB  
Article
Molecular Analysis of Carbapenem and Aminoglycoside Resistance Genes in Carbapenem-Resistant Pseudomonas aeruginosa Clinical Strains: A Challenge for Tertiary Care Hospitals
by Aamir Jamal Gondal, Nakhshab Choudhry, Ammara Niaz and Nighat Yasmin
Antibiotics 2024, 13(2), 191; https://doi.org/10.3390/antibiotics13020191 - 16 Feb 2024
Cited by 2 | Viewed by 2244
Abstract
Carbapenem-resistant Pseudomonas aeruginosa (P. aeruginosa) strains have become a global threat due to their remarkable capability to survive and disseminate successfully by the acquisition of resistance genes. As a result, the treatment strategies have been severely compromised. Due to the insufficient [...] Read more.
Carbapenem-resistant Pseudomonas aeruginosa (P. aeruginosa) strains have become a global threat due to their remarkable capability to survive and disseminate successfully by the acquisition of resistance genes. As a result, the treatment strategies have been severely compromised. Due to the insufficient available data regarding P. aeruginosa resistance from Pakistan, we aimed to investigate the resistance mechanisms of 249 P. aeruginosa strains by antimicrobial susceptibility testing, polymerase chain reaction for the detection of carbapenemases, aminoglycoside resistance genes, extended-spectrum beta-lactamases (ESBLs), sequence typing and plasmid typing. Furthermore, we tested silver nanoparticles (AgNPs) to evaluate their in vitro sensitivity against antimicrobial-resistant P. aeruginosa strains. We observed higher resistance against antimicrobials in the general surgery ward, general medicine ward and wound samples. Phenotypic carbapenemase-producer strains comprised 80.7% (201/249) with 89.0% (179/201) demonstrating genes encoding carbapenemases: blaNDM-1 (32.96%), blaOXA48 (37.43%), blaIMP (7.26%), blaVIM (5.03%), blaKPC-2 (1.12%), blaNDM-1/blaOXA48 (13.97%), blaOXA-48/blaVIM (1.68%) and blaVIM/blaIMP (0.56%). Aminoglycoside-modifying enzyme genes and 16S rRNA methylase variants were detected in 43.8% (109/249) strains: aac(6′)-lb (12.8%), aac(3)-lla (12.0%), rmtB (21.1%), rmtC (11.0%), armA (12.8%), rmtD (4.6%), rmtF (6.4%), rmtB/aac(3)-lla (8.2%), rmtB/aac(6′)-lla (7.3%) and rmtB/armA (3.6%). In total, 43.0% (77/179) of the strains coharbored carbapenemases and aminoglycoside resistance genes with 83.1% resistant to at least 1 agent in 3 or more classes and 16.9% resistant to every class of antimicrobials tested. Thirteen sequence types (STs) were identified: ST235, ST277, ST234, ST170, ST381, ST175, ST1455, ST1963, ST313, ST207, ST664, ST357 and ST348. Plasmid replicon types IncFI, IncFII, IncA/C, IncL/M, IncN, IncX, IncR and IncFIIK and MOB types F11, F12, H121, P131 and P3 were detected. Meropenem/AgNPs and Amikacin/AgNPs showed enhanced antibacterial activity. We reported the coexistence of carbapenemases and aminoglycoside resistance genes among carbapenem-resistant P. aeruginosa with diverse clonal lineages from Pakistan. Furthermore, we highlighted AgNP’s potential role in handling future antimicrobial resistance concerns. Full article
(This article belongs to the Special Issue Carbapenem Resistant Gram-Negative Pathogens—a Comprehensive Approach to Acinetobacter, Pseudomonas, Enterobacteriaceae, and Stenotrophomonas: A Global Healthcare Threat)
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10 pages, 931 KiB  
Article
Poor Sensitivity of the MALDI Biotyper® MBT Subtyping Module for Detection of Klebsiella pneumoniae Carbapenemase (KPC) in Klebsiella Species
by Luz Cuello, Judith Alvarez Otero, Kerryl E. Greenwood-Quaintance, Liang Chen, Blake Hanson, Jinnethe Reyes, Lauren Komarow, Lizhao Ge, Zane D. Lancaster, Garrett G. Gordy, Audrey N. Schuetz and Robin Patel
Antibiotics 2023, 12(9), 1465; https://doi.org/10.3390/antibiotics12091465 - 20 Sep 2023
Cited by 1 | Viewed by 1822
Abstract
Rapid detection of Klebsiella pneumoniae carbapenemase (KPC) in the Klebsiella species is desirable. The MALDI Biotyper® MBT Subtyping Module (Bruker Daltonics) uses an algorithm that detects a peak at ~11,109 m/z corresponding to a protein encoded by the p019 gene to detect [...] Read more.
Rapid detection of Klebsiella pneumoniae carbapenemase (KPC) in the Klebsiella species is desirable. The MALDI Biotyper® MBT Subtyping Module (Bruker Daltonics) uses an algorithm that detects a peak at ~11,109 m/z corresponding to a protein encoded by the p019 gene to detect KPC simultaneously with organism identification by a matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI-ToF MS). Here, the subtyping module was evaluated using 795 clinical Klebsiella isolates, with whole genome sequences used to assess for blaKPC and p019. For the isolates identified as KPC positive by sequencing, the overall sensitivity of the MALDI-ToF MS subtyping module was 239/574 (42%) with 100% specificity. For the isolates harboring p019, the subtyping module showed a sensitivity of 97% (239/246) and a specificity of 100%. The subtyping module had poor sensitivity for the detection of blaKPC-positive Klebsiella isolates, albeit exhibiting excellent specificity. The poor sensitivity was a result of p019 being present in only 43% of the blaKPC-positive Klebsiella isolates. Full article
(This article belongs to the Special Issue Carbapenem Resistant Gram-Negative Pathogens—a Comprehensive Approach to Acinetobacter, Pseudomonas, Enterobacteriaceae, and Stenotrophomonas: A Global Healthcare Threat)
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12 pages, 1964 KiB  
Article
Predictors of Mortality in Patients with Infections Due to Carbapenem-Resistant Gram-Negative Bacteria
by Hector Orlando Rivera-Villegas, Bernardo Alfonso Martinez-Guerra, Rosalia Garcia-Couturier, Luis Fernando Xancal-Salvador, Veronica Esteban-Kenel, Ricardo Antonio Jaimes-Aquino, Miguel Mendoza-Rojas, Axel Cervantes-Sánchez, Steven Méndez-Ramos, Jorge Eduardo Alonso-Montoya, Diana Munguia-Ramos, Karla Maria Tamez-Torres, Carla Marina Roman-Montes, Sandra Rajme-Lopez, Areli Martínez-Gamboa, Miriam Bobadilla-del-Valle, Maria Fernanda Gonzalez-Lara, Jose Sifuentes-Osornio and Alfredo Ponce-de-Leon
Antibiotics 2023, 12(7), 1130; https://doi.org/10.3390/antibiotics12071130 - 29 Jun 2023
Cited by 3 | Viewed by 1780
Abstract
Introduction: Infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) are a significant cause of mortality and represent a serious challenge to health systems. The early identification of mortality predictors could guide appropriate treatment and follow-up. We aimed to identify the factors associated with 90-day [...] Read more.
Introduction: Infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) are a significant cause of mortality and represent a serious challenge to health systems. The early identification of mortality predictors could guide appropriate treatment and follow-up. We aimed to identify the factors associated with 90-day all-cause mortality in patients with CR-GNB infections. Methods: We conducted a cohort study from 1 January 2019 to 30 April 2022. The primary outcome was death from any cause during the first 90 days after the date of the first CR-GNB-positive culture. Secondary outcomes included infection relapse, invasive mechanical ventilation during follow-up, need for additional source control, acute kidney injury, Clostridioides difficile infection, and all-cause hospital admission after initial discharge. Bivariate and multivariate Cox-proportional hazards models were constructed to identify the factors independently associated with 90-day all-cause mortality. Results: A total of 225 patients with CR-GNB infections were included. Death occurred in 76 (34%) cases. The most-reported comorbidities were immunosuppression (43%), arterial hypertension (35%), and COVID-19 (25%). The median length of stay in survivors was 18 days (IQR 10–34). Mechanical ventilation and ICU admission after diagnosis occurred in 8% and 11% of cases, respectively. Both infection relapse and rehospitalisation occurred in 18% of cases. C. difficile infection was diagnosed in 4% of cases. Acute kidney injury was documented in 22% of patients. Mechanical ventilation after diagnosis, ICU admission after diagnosis, and acute kidney injury in the first ten days of appropriate treatment were more frequently reported among non-survivors. In the multivariate analysis, age (HR 1.19 (95%CI 1.00–1.83)), immunosuppression (HR 1.84 (95%CI 1.06–3.18)), and septic shock at diagnosis (HR 2.40 (95% 1.41–4.08)) had an independent association with death during the first 90 days after the CR-GNB infection diagnosis. Receiving antibiogram-guided appropriate treatment was independently associated with a lower risk of death (HR 0.25 (95%CI 0.14–0.46)). Conclusions: The presence of advanced age, immunosuppression, septic shock at diagnosis, and inappropriate treatment are associated with higher 90-day all-cause mortality in hospitalised patients with infections due to CR-GNB. Recognition of the risk factors for adverse outcomes could further assist in patient care and the design of interventional studies that address the severe and widespread problem that is carbapenem resistance. Full article
(This article belongs to the Special Issue Carbapenem Resistant Gram-Negative Pathogens—a Comprehensive Approach to Acinetobacter, Pseudomonas, Enterobacteriaceae, and Stenotrophomonas: A Global Healthcare Threat)
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Review

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15 pages, 793 KiB  
Review
Practical Application of Aztreonam-Avibactam as a Treatment Strategy for Ambler Class B Metallo-β-Lactamase Producing Enterobacteriaceae
by Darren W. Wong
Antibiotics 2024, 13(8), 766; https://doi.org/10.3390/antibiotics13080766 - 14 Aug 2024
Viewed by 1397
Abstract
Carbapenem-resistant Enterobacteriaceae infections are a considerable challenge for clinicians. In recent years, novel antibiotic options have resulted in a tremendous advance in medical therapy; however, current treatment options are primarily effective for resistance derived from serine-based carbapenemases. The Ambler class B metallo-β-lactamases (MBLs) [...] Read more.
Carbapenem-resistant Enterobacteriaceae infections are a considerable challenge for clinicians. In recent years, novel antibiotic options have resulted in a tremendous advance in medical therapy; however, current treatment options are primarily effective for resistance derived from serine-based carbapenemases. The Ambler class B metallo-β-lactamases (MBLs) remain a critical challenge with decidedly fewer effective options. One intriguing option for these MBL pathogens is the combination of ceftazidime-avibactam with aztreonam. While clinical experience with this regimen is limited, in vitro studies are promising, and limited case reports describe success with this regimen; however, significant challenges preclude widespread adoption of this novel treatment regimen. A systemic literature review was performed to offer recommendations based on current evidence for a practical strategy on how to best integrate the use of aztreonam with avibactam combination therapy. Full article
(This article belongs to the Special Issue Carbapenem Resistant Gram-Negative Pathogens—a Comprehensive Approach to Acinetobacter, Pseudomonas, Enterobacteriaceae, and Stenotrophomonas: A Global Healthcare Threat)
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Other

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12 pages, 747 KiB  
Systematic Review
Carbapenem-Resistant Enterobacteriaceae Bacteremia in Pediatric Patients in Latin America and the Caribbean: A Systematic Review and Meta-Analysis
by Silvina Ruvinsky, Carla Voto, Macarena Roel, Victoria Portillo, Gabriela Naranjo Zuñiga, Rolando Ulloa-Gutierrez, Daniel Comandé, Agustín Ciapponi, Gabriela Aboud, Martín Brizuela and Ariel Bardach
Antibiotics 2024, 13(12), 1117; https://doi.org/10.3390/antibiotics13121117 - 22 Nov 2024
Abstract
Background: Data on the health impact of carbapenem-resistant Enterobacteriaceae bloodstream infections (CRE-BSIs) in pediatric populations from Latin America and the Caribbean (LAC) are limited. This systematic review aims to examine the demographic, clinical, and microbiological aspects and resource utilization of this infection in [...] Read more.
Background: Data on the health impact of carbapenem-resistant Enterobacteriaceae bloodstream infections (CRE-BSIs) in pediatric populations from Latin America and the Caribbean (LAC) are limited. This systematic review aims to examine the demographic, clinical, and microbiological aspects and resource utilization of this infection in children from this region. Methods: This systematic review investigates the impact of CRE-BSIs in pediatric populations across LAC. Following the Cochrane methodology and PRISMA/MOOSE guidelines, we conducted an extensive search of different databases, including MEDLINE/PubMed, LILACS (SciELO), CENTRAL, CINAHL, Embase (Ovid), the Cochrane Library, and the World Health Organization (WHO) database, and relevant websites for published articles between January 2012 and September 2024. The review included studies on hospitalized patients under 19 years of age with CRE-BSIs. Results: Fourteen studies involving 189 patients were analyzed. Most cases were reported from Brazil, Argentina, Colombia, and Paraguay. The median age of the patients was 35 months. Key risk factors included immunocompromised status, invasive procedures, carbapenem use, and colonization. The infections were predominantly hospital-acquired, with Klebsiella pneumoniae and Serratia spp. being the most common pathogens. KPC and NDM were the primary resistance mechanisms. Most patients received combination antimicrobial therapy for a median of 17 days. An alarmingly high mortality rate at 34% was found. Conclusions: Our findings highlight that CRE-BSIs pose a significant threat to children with underlying conditions in LAC, leading to substantial morbidity and mortality. Implementing robust antimicrobial stewardship programs and effective infection control measures are crucial to curbing the spread of CRE-BSIs in the region. This review underscores the need for targeted interventions and further research to address this critical public health concern in pediatric populations across LAC. Full article
(This article belongs to the Special Issue Carbapenem Resistant Gram-Negative Pathogens—a Comprehensive Approach to Acinetobacter, Pseudomonas, Enterobacteriaceae, and Stenotrophomonas: A Global Healthcare Threat)
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