scholarly journals Current Promising Antibiotics and Future Approaches in Combating Carbapenemase-Producing Enterobacteriaceae

Proceedings ◽  
2021 ◽  
Vol 66 (1) ◽  
pp. 25
Author(s):  
Corneliu Ovidiu Vrancianu ◽  
Elena Georgiana Dobre ◽  
Irina Gheorghe ◽  
Ilda Barbu ◽  
Roxana Elena Cristian ◽  
...  

Carbapenem-resistant (CR) Gram-negative bacilli, including Enterobacteriaceae and the non-fermenters, represent the most notorious pathogens due to the high incidence of morbidity and mortality, especially in immunocompromised patients in intensive care units. Carbapenem resistance is mainly associated with the production of carbapenemases, which are β-lactamases belonging to different Ambler classes (A, B, D) that can be encoded by both chromosomal and plasmid-mediated genes. These enzymes represent the most potent β-lactamases, hydrolyzing a wide variety of β-lactams, including carbapenems, cephalosporins, penicillin, and aztreonam. The major issues associated with carbapenemase production are both clinical, posing significant challenges in the treatment of healthcare-associated infections by compromising the activity of the last-resort antibiotics, and epidemiological, due to their dissemination across almost all geographic regions. An important advancement is a handful of newly launched antibiotics targeting some of the current most problematic Gram-negative pathogens, namely carbapenem-resistant Enterobacteriaceae (CRE). The most appropriate antimicrobial therapy to treat CRE infections is still controversial. Combination therapy is preferred over monotherapy due to its broad-spectrum coverage, synergic activity, and low probability of selecting resistance. In this mini-review, current and future promising antibiotics that are currently under investigation for winning the war against the emerging CRE are discussed.

Author(s):  
Sara Kotb ◽  
Meghan Lyman ◽  
Ghada Ismail ◽  
Mohammad Abd El Fattah ◽  
Samia A. Girgis ◽  
...  

Abstract Objective To describe the epidemiology of carbapenem-resistant Enterobacteriaceae (CRE) healthcare-associated infections (HAI) in Egyptian hospitals reporting to the national HAI surveillance system. Methods Design: Descriptive analysis of CRE HAIs and retrospective observational cohort study using national HAI surveillance data. Setting: Egyptian hospitals participating in the HAI surveillance system. The patient population included patients admitted to the intensive care unit (ICU) in participating hospitals. Enterobacteriaceae HAI cases were Klebsiella, Escherichia coli, and Enterobacter isolates from blood, urine, wound or respiratory specimen collected on or after day 3 of ICU admission. CRE HAI cases were those resistant to at least one carbapenem. For CRE HAI cases reported during 2011–2017, a hospital-level and patient-level analysis were conducted using only the first CRE isolate by pathogen and specimen type for each patient. For facility, microbiology, and clinical characteristics, frequencies and means were calculated among CRE HAI cases and compared with carbapenem-susceptible Enterobacteriaceae HAI cases through univariate and multivariate logistic regression using STATA 13. Results There were 1598 Enterobacteriaceae HAI cases, of which 871 (54.1%) were carbapenem resistant. The multivariate regression analysis demonstrated that carbapenem resistance was associated with specimen type, pathogen, location prior to admission, and length of ICU stay. Between 2011 and 2017, there was an increase in the proportion of Enterobacteriaceae HAI cases due to CRE (p-value = 0.003) and the incidence of CRE HAIs (p-value = 0.09). Conclusions This analysis demonstrated a high and increasing burden of CRE in Egyptian hospitals, highlighting the importance of enhancing infection prevention and control (IPC) programs and antimicrobial stewardship activities and guiding the implementation of targeted IPC measures to contain CRE in Egyptian ICU’s .


Author(s):  
Robert J. Clifford ◽  
Donna Newhart ◽  
Maryrose R. Laguio-Vila ◽  
Jennifer L. Gutowski ◽  
Melissa Z. Bronstein ◽  
...  

Abstract Objective: To quantitatively evaluate relationships between infection preventionists (IPs) staffing levels, nursing hours, and rates of 10 types of healthcare-associated infections (HAIs). Design and setting: An ambidirectional observation in a 528-bed teaching hospital. Patients: All inpatients from July 1, 2012, to February 1, 2021. Methods: Standardized US National Health Safety Network (NHSN) definitions were used for HAIs. Staffing levels were measured in full-time equivalents (FTE) for IPs and total monthly hours worked for nurses. A time-trend analysis using control charts, t tests, Poisson tests, and regression analysis was performed using Minitab and R computing programs on rates and standardized infection ratios (SIRs) of 10 types of HAIs. An additional analysis was performed on 3 stratifications: critically low (2–3 FTE), below recommended IP levels (4–6 FTE), and at recommended IP levels (7–8 FTE). Results: The observation covered 1.6 million patient days of surveillance. IP staffing levels fluctuated from ≤2 IP FTE (critically low) to 7–8 IP FTE (recommended levels). Periods of highest catheter-associated urinary tract infection SIRs, hospital-onset Clostridioides difficile and carbapenem-resistant Enterobacteriaceae infection rates, along with 4 of 5 types of surgical site SIRs coincided with the periods of lowest IP staffing levels and the absence of certified IPs and a healthcare epidemiologist. Central-line–associated bloodstream infections increased amid lower nursing levels despite the increased presence of an IP and a hospital epidemiologist. Conclusions: Of 10 HAIs, 8 had highest incidences during periods of lowest IP staffing and experience. Some HAI rates varied inversely with levels of IP staffing and experience and others appeared to be more influenced by nursing levels or other confounders.


Pathogens ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 667
Author(s):  
Claire Hayward ◽  
Kirstin E. Ross ◽  
Melissa H. Brown ◽  
Harriet Whiley

Healthcare-associated infections (HAIs) are one of the most common patient complications, affecting 7% of patients in developed countries each year. The rise of antimicrobial resistant (AMR) bacteria has been identified as one of the biggest global health challenges, resulting in an estimated 23,000 deaths in the US annually. Environmental reservoirs for AMR bacteria such as bed rails, light switches and doorknobs have been identified in the past and addressed with infection prevention guidelines. However, water and water-related devices are often overlooked as potential sources of HAI outbreaks. This systematic review examines the role of water and water-related devices in the transmission of AMR bacteria responsible for HAIs, discussing common waterborne devices, pathogens, and surveillance strategies. AMR strains of previously described waterborne pathogens including Pseudomonas aeruginosa, Mycobacterium spp., and Legionella spp. were commonly isolated. However, methicillin-resistant Staphylococcus aureus and carbapenem-resistant Enterobacteriaceae that are not typically associated with water were also isolated. Biofilms were identified as a hot spot for the dissemination of genes responsible for survival functions. A limitation identified was a lack of consistency between environmental screening scope, isolation methodology, and antimicrobial resistance characterization. Broad universal environmental surveillance guidelines must be developed and adopted to monitor AMR pathogens, allowing prediction of future threats before waterborne infection outbreaks occur.


2020 ◽  
Vol Volume 13 ◽  
pp. 3991-4002 ◽  
Author(s):  
Rabab R Makharita ◽  
Iman El-kholy ◽  
Helal F Hetta ◽  
Moahmed Abdelaziz ◽  
Fatma Hagagy ◽  
...  

Author(s):  
Viviane Maria de Carvalho Hessel Dias ◽  
Daniela Maria Waszak da Silva ◽  
Marion Burger ◽  
Alcides Augusto Souto de Oliveira ◽  
Patrícia de Jesus Capelo da Fonseca ◽  
...  

2013 ◽  
Vol 7 (2) ◽  
pp. 06-12
Author(s):  
Zahidul Hasan ◽  
Md. Kamrul Islam ◽  
Arifa Hossain

Recently non-fermenting Gram negative rods (NFGNR) are playing an important role in healthcare associated infections. This observational study in a tertiary care hospital of Dhaka city conducted during 01August 2007 to 30 June 2013 found that 34.8% isolated organisms from patients with healthcare associated infections were NFGNR. Majority (74.3 %) of these infections were occurring inside critical care areas. Pseudomonas and Acinetobacter together constituted 79.6% of the total NFGNR whereas Burkholderia cephacia complex (15.4%), Stenotrophomonas (4.3%) and Chryseobacterium species (0.7%) combined constituted remaining 20.4%. Out of total NFGNRs, Pseudomonas was responsible for highest number of catheter associated urinary tract infections (55.6%), ventilator associated pneumonia (46.3%), respiratory tract infection (65.8%) and surgical site infection (70.6%). Blood stream infection was predominantly caused by Burkholderia cephacia complex (33.5%) and Acinetobacter spp. (39.5%). Other than colistin most of the organisms were resistant to antibiotics commonly recommended for NFGNR.DOI: http://dx.doi.org/10.3329/bjmm.v7i2.19326 Bangladesh J Med Microbiol 2013; 07(02): 6-12


Author(s):  
Nisha Patidar ◽  
Nitya Vyas ◽  
Shanoo Sharma ◽  
Babita Sharma

Abstract Objective Carbapenems are last resort antibiotics for multidrug-resistant Enterobacteriaceae. However, resistance to carbapenem is increasing at an alarming rate worldwide leading to major therapeutic failures and increased mortality rate. Early and effective detection of carbapenemase producing carbapenem-resistant Enterobacteriaceae (CRE) is therefore key to control dissemination of carbapenem resistance in nosocomial as well as community-acquired infection. The aim of present study was to evaluate efficacy of Modified strip Carba NP (CNP) test against Modified Hodge test (MHT) for early detection of carbapenemase producing Enterobacteriaceae (CPE). Material and Methods Enterobacteriaceae isolated from various clinical samples were screened for carbapenem resistance. A total of 107 CRE were subjected to MHT and Modified strip CNP test for the detection of CPE. Statistical Analysis It was done on Statistical Package for the Social Sciences (SPSS) software, IBM India; version V26. Nonparametric test chi-square and Z-test were used to analyze the results within a 95% level of confidence. Results Out of 107 CRE, 94 (88%) were phenotypically confirmed as carbapenemase producer by Modified strip CNP test and 46 (43%) were confirmed by Modified Hodge Test (MHT). Thirty-eight (36%) isolates showed carbapenemase production by both MHT and CNP test, 56 isolates (52%) were CNP test positive but MHT negative, eight (7%) isolates were MHT positive but CNP test negative and five (5%) isolates were both MHT and CNP test negative. There is statistically significant difference in efficiency of Modified CNP test and MHT (p < 0.05). Conclusion Modified strip CNP test is simple and inexpensive test which is easy to perform and interpret and gives rapid results in less than 5 minutes. It has high degree of sensitivity and specificity. Modified strip CNP test shows significantly higher detection capacity for carbapenemase producers as compared with MHT.


Author(s):  
Hari P. Nepal ◽  
Rama Paudel

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.


2019 ◽  
Vol 2 (1) ◽  
pp. 8-14
Author(s):  
Beauty Novianty ◽  
Ella Amalia ◽  
Ziske Maritska ◽  
Yuwono Yuwono ◽  
Lusia Hayati

Background: Over the past decade, numbers of Carbapenemase Producing-Carbapenem Resistant Enterobacteriaceae (CP-CRE) has been increasing worldwide and it has been becoming a threat because of its resistance against carbapenem which is considered as the “last resort” antibiotic. Therapy options for its infection are still limited. Aminoglycoside serves as one of the most commonly used antibiotics, but the resistance against it has already been presented for a long time. Aminoglycoside Modifying Enzyme (AME) is the most important resistance mechanism against aminoglycoside. AAC(6’)-Ib enzyme is one of the most common AME produced by the gram-negative bacteria.Objectives: This study wished to identify the gene of this enzyme among CRE isolated from infected Indonesian patients in Dr. Mohammad Hoesin Hospital Palembang.Methods: Twenty-eight isolates collected from CRE-infected patients identified by Vitek 2 Compact (bioMerieux, USA) in dr. Mohammad Hoesin Hospital Palembang during September—November 2017. AAC(6’)-Ib gene was identified using PCR method, then visualize by electrophoresis. The result is then analyzed by comparing it with a susceptibility test.  Results: Out of 28 samples, AAC(6’)-Ib is identified in 22 (78.57%) samples. Samples with AAC(6’)-Ib showed to be less resistant to various antibiotics, significantly to amikacin (p=0.023).Conclusion: AAC(6’)-Ib gene is found in most of samples implying its frequent occurrence in Indonesian patients.


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