scholarly journals Environmental Prevalence of Carbapenem Resistance Enterobacteriaceae (CRE) in a Tropical Ecosystem in India: Human Health Perspectives and Future Directives

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 174 ◽  
Author(s):  
Sivalingam ◽  
Poté ◽  
Prabakar

In the past few decades, infectious diseases have become increasingly challenging to treat, which is explained by the growing number of antibiotic-resistant bacteria. Notably, carbapenem-resistant Enterobacteriaceae (CRE) infections at global level attribute a vast, dangerous clinical threat. In most cases, there are enormous difficulties for CRE infection except a few last resort toxic drugs such as tigecycline and colistin (polymyxin E). Due to this, CRE has now been categorized as one among the three most dangerous multidrug resistance (MDR) pathogens by the US Centres for Disease Control and Prevention (CDC). Considering this, the study of the frequency of CRE infections and the characterization of CRE is an important area of research in clinical settings. However, MDR bacteria are not only present in hospitals but are spreading more and more into the environment, thereby increasing the risk of infection with resistant bacteria outside the hospital. In this context, developing countries are a global concern where environmental regulations are often insufficient. It seems likely that overcrowding, poor sanitation, socioeconomic status, and limited infrastructures contribute to the rapid spread of MDR bacteria, becoming their reservoirs in the environment. Thus, in this review, we present the occurrence of CRE and their resistance determinants in different environmental compartments in India.

2020 ◽  
Vol 41 (S1) ◽  
pp. s356-s357
Author(s):  
Tomasz Kasperski ◽  
Biophage Pharma S.A. Kraków ◽  
Agnieszka Chmielarczyk ◽  
Monika Pomorska-Wesolowska ◽  
Dorota Romaniszyn ◽  
...  

Background:Acinetobacter spp are gram-negative bacteria that have emerged as a leading cause of hospital-associated infections, most often in the intensive care unit (ICU) setting. This is particularly important in Poland, where the prevalence of A. baumannii in various types of infections, including bloodstream infection (BSI), pneumonia, skin and soft-tissue infection (SSTI), and urinary tract infection (UTI) is higher than in neighboring countries. Recently, other Acinetobacter spp, including A. lwoffii or A. ursingii, have been found to be clinically relevant. In Poland, we have also observed a very rapid increase in antimicrobial resistance, significantly faster for A. baumannii than for other nosocomial pathogens. Methods: A study was conducted in 12 southern Polish hospitals, including 3 ICUs, from January 1 to December 31, 2018. Only adult hospitalized patients were included. Strains were identified using the MALDI-TOF method. Carbapenem resistance was determined using the minimum inhibitory concentration (MIC). Results: During the study, 194 strains belonging to the Acinetobacter genus were isolated. A. baumannii was the dominant species, 88.1% (n = 171), and 23 isolates (11.9%) were other Acinetobacter spp: A. ursingii (n = 5), A. lwofii (n = 4), A. haemolyticus (n = 4), A. junii (n = 3), A. radioresistens (n = 2), A. bereziniae (n = 2), and A. johnsonii (n = 2). Moreover, 15 Acinetobacter strains were collected from ICUs. The most Acinetobacter strains were isolated from SSTIs (n = 115) from non-ICU settings. Non–A. baumannii strains were also most frequently isolated from SSTIs; they constituted 11.3% of all Acinetobacter strains from this type of infection (n = 13). The total Acinetobacter prevalence was 2.6%, whereas the prevalence in the ICU setting was 7%. Acinetobacter prevalence in SSTIs was 10.4%. In pneumonia, Acinetobacter prevalence was 18.6% for ICUs (n = 13) and 2.7% for non-ICUs (n = 46). Strains from UTIs were isolated only with the non-ICU setting, and their prevalence was 0.7% (n = 14). More than half of the tested strains (52.1%) were resistant to carbapenems, but all non–A. baumannii strains were susceptible. The highest resistance to carbapenems was among strains from pneumonia cases in ICUs (58.3%) and resistance among all strains isolated from ICU was 50%. However, even higher resistance was noted among SSTI strains from non-ICUs (61.7%). Conclusions: Increasingly, more than A. baumannii, other species among Acinetobacter strains are isolated from patients hospitalized in Polish hospitals. To assess the significance of non–A. baumannii spp in clinical settings, precise species identification is needed. Therefore, the diagnostic methods used must be improved. Carbapenem-resistant A. baumannii infections are the biggest problem in pneumonia patients in ICUs and in SSTI patients in other hospital departments. Carbapenem resistance occurs in a very high percentage of A. baumannii strains; among non–A. baumannii strains it is not yet a therapeutic problem.Funding: NoneDisclosures: None


Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 495
Author(s):  
Masateru Nishiyama ◽  
Susan Praise ◽  
Keiichi Tsurumaki ◽  
Hiroaki Baba ◽  
Hajime Kanamori ◽  
...  

There is increasing attention toward factors that potentially contribute to antibiotic resistance (AR), as well as an interest in exploring the emergence and occurrence of antibiotic resistance bacteria (ARB). We monitored six ARBs that cause hospital outbreaks in wastewater influent to highlight the presence of these ARBs in the general population. We analyzed wastewater samples from a municipal wastewater treatment plant (MWWTP) and hospital wastewater (HW) for six species of ARB: Carbapenem-resistant Enterobacteria (CARBA), extended-spectrum β-lactamase producing Enterobacteria (ESBL), multidrug-resistant Acinetobacter (MDRA), multidrug-resistant Pseudomonas aeruginosa (MDRP), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococci (VRE). We registered a high percentage of ARBs in MWWTP samples (>66%) for all ARBs except for MDRP, indicating a high prevalence in the population. Percentages in HW samples were low (<78%), and no VRE was detected throughout the study. CARBA and ESBL were detected in all wastewater samples, whereas MDRA and MRSA had a high abundance. This result demonstrated the functionality of using raw wastewater at MWWTP to monitor the presence and extent of ARB in healthy populations. This kind of surveillance will contribute to strengthening the efforts toward reducing ARBs through the detection of ARBs to which the general population is exposed.


2019 ◽  
Vol 476 (5) ◽  
pp. 795-808 ◽  
Author(s):  
Jyoti Singh Tomar ◽  
Rama Krishna Peddinti ◽  
Ramakrishna V. Hosur

AbstractAntibiotic-resistant bacteria pose the greatest threat to human health. Among the list of such bacteria released by WHO, carbapenem-resistant Acinetobacter baumannii, for which almost no treatment exists, tops the list. A. baumannii is one of the most troublesome ESKAPE pathogens and mechanisms that have facilitated its rise as a successful pathogen are not well studied. Efforts in this direction have resulted in the identification of Hpa2-Ab, an uncharacterized histone acetyltransferase enzyme of GNAT superfamily. Here, we show that Hpa2-Ab confers resistance against aminoglycoside antibiotics using Escherichia coli DH5α strains in which Hpa2 gene is expressed. Resistivity for aminoglycoside antibiotics is demonstrated with the help of CLSI-2010 and KB tests. Isothermal titration calorimetry, MALDI and acetylation assays indicate that conferred resistance is an outcome of evolved antibiotic acetylation capacity in this. Hpa2 is known to acetylate nuclear molecules; however, here it is found to cross its boundary and participate in other functions. An array of biochemical and biophysical techniques were also used to study this protein, which demonstrates that Hpa2-Ab is intrinsically oligomeric in nature, exists primarily as a dimer and its interface is mainly stabilized by hydrophobic interactions. Our work demonstrates an evolved survival strategy by A. baumannii and provides insights into the mechanism that facilitates it to rise as a successful pathogen.


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.


Author(s):  
John Njeru

The epidemiology of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE) and their role in the development and spread of multidrug resistance (MDR) is not well characterized in sub-Saharan Africa (SSA). Carbapenems possess a broad spectrum of activity and are often reserved for the treatment of MDR infections in developed countries. However, the emergence of carbapenem resistance is increasingly being reported and therefore presents a significant public health threat. Although carbapenems are generally unavailable in African hospitals due to high cost, a small number of studies have reported the occurrence of carbapenem-resistant bacteria (CRB) in SSA. This, therefore, shows that carbapenem resistance (CR) is emerging in Africa. Thus, there is a critical need for deploying robust national and regional multidisciplinary, collaborative, and regulatory approaches aiming at elucidating the epidemiology of CR, its burden on the health care system, and strategies for compacting the development and spread of CR. This report hopes to highlight the epidemiology of carbapenem resistance and the main drivers of antibiotic resistance in SSA and proposes future strategies that can be used to combat the emergence of carbapenem resistance in the region


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Si Li ◽  
Xiaonv Duan ◽  
Yuan Peng ◽  
Yongyu Rui

Abstract Background Carbapenem resistance among Acinetobacter species has become a life-threatening problem. As a last resort in the treatment of gram-negative bacteria infection, resistance to colistin is also a serious problem. The aim of study was to analyze the mechanism of resistance and perform genotyping of carbapenem-resistant Acinetobacter from clinical infection and fecal survey samples in Southern China. Methods One hundred seventy and 74 carbapenem-resistant Acinetobacter were isolated from clinical infection samples and fecal survey samples, respectively. We detected the related genes, including carbapenemase genes (blaKPC, blaIMP, blaSPM, blaVIM, blaNDM, blaOXA-23-like, blaOXA-24/40-like, blaOXA-51-like, and blaOXA-58-like), colistin resistance-related genes (mcr-1, mcr-2, mcr-3, mcr-4, and mcr-5), a porin gene (carO), efflux pump genes (adeA, adeB, adeC, adeI, adeJ, and adeK), mobile genetic element genes (intI1, intI2, intI3, tnpU, tnp513, IS26, ISAba1, and ISAba125), and the integron variable region. Genotyping was analyzed by enterobacterial repetitive intergenic consensus (ERIC)-PCR and dendrogram cluster analysis. Results Among the 244 carbapenem-resistant Acinetobacter, the common carbapenemase-positive genes included the following: blaOXA-51-like, 183 (75.00%); blaOXA-23-like, 174 (71.30%); blaNDM-1, 57 (23.40%); and blaOXA-58-like, 30 (12.30%). The coexistence of mcr-1 and blaNDM-1 in five strains of A. junii was found for the first time. Eleven distinct carO gene variants were detected in 164 (67.20%) strains, and ten novel variants, which shared 92–99% identity with sequences in the Genbank database, were first reported. Efflux system genes were present in approximately 70% of the isolates; adeABC and adeIJK were observed in 76.23 and 72.13%, respectively. Class 1 integrons were detected in 180 (73.80%) strains and revealed that four gene cassette arrays contained 11 distinct genes. The genotyping by ERIC-PCR demonstrated a high genetic diversity of non-baumannii Acinetobacter, and greater than 90% similarity to A. baumannii. Conclusions The blaNDM-1 gene was identified in up to 77% of the carbapenem-resistant Acinetobacter isolated from fecal survey samples, indicating that the gut might be a reservoir of resistant opportunistic bacteria. Intestinal bacteria can be transmitted through the fecal-hand, which is a clinical threat, thus, the monitoring of carbapenem-resistant bacteria from inpatients’ feces should be improved, especially for patients who have been using antibiotics for a long time.


mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Jun-ichi Wachino ◽  
Wanchun Jin ◽  
Kouji Kimura ◽  
Hiromasa Kurosaki ◽  
Ayato Sato ◽  
...  

ABSTRACT Production of metallo-β-lactamases (MBLs), which hydrolyze carbapenems, is a cause of carbapenem resistance in Enterobacteriaceae. Development of effective inhibitors for MBLs is one approach to restore carbapenem efficacy in carbapenem-resistant Enterobacteriaceae (CRE). We report here that sulfamoyl heteroarylcarboxylic acids (SHCs) can competitively inhibit the globally spreading and clinically relevant MBLs (i.e., IMP-, NDM-, and VIM-type MBLs) at nanomolar to micromolar orders of magnitude. Addition of SHCs restored meropenem efficacy against 17/19 IMP-type and 7/14 NDM-type MBL-producing Enterobacteriaceae to satisfactory clinical levels. SHCs were also effective against IMP-type MBL-producing Acinetobacter spp. and engineered Escherichia coli strains overproducing individual minor MBLs (i.e., TMB-2, SPM-1, DIM-1, SIM-1, and KHM-1). However, SHCs were less effective against MBL-producing Pseudomonas aeruginosa. Combination therapy with meropenem and SHCs successfully cured mice infected with IMP-1-producing E. coli and dually NDM-1/VIM-1-producing Klebsiella pneumoniae clinical isolates. X-ray crystallographic analyses revealed the inhibition mode of SHCs against MBLs; the sulfamoyl group of SHCs coordinated to two zinc ions, and the carboxylate group coordinated to one zinc ion and bound to positively charged amino acids Lys224/Arg228 conserved in MBLs. Preclinical testing revealed that the SHCs showed low toxicity in cell lines and mice and high stability in human liver microsomes. Our results indicate that SHCs are promising lead compounds for inhibitors of MBLs to combat MBL-producing CRE. IMPORTANCE Carbapenem antibiotics are the last resort for control of severe infectious diseases, bloodstream infections, and pneumonia caused by Gram-negative bacteria, including Enterobacteriaceae. However, carbapenem-resistant Enterobacteriaceae (CRE) strains have spread globally and are a critical concern in clinical settings because CRE infections are recognized as a leading cause of increased mortality among hospitalized patients. Most CRE produce certain kinds of serine carbapenemases (e.g., KPC- and GES-type β-lactamases) or metallo-β-lactamases (MBLs), which can hydrolyze carbapenems. Although effective MBL inhibitors are expected to restore carbapenem efficacy against MBL-producing CRE, no MBL inhibitor is currently clinically available. Here, we synthesized 2,5-diethyl-1-methyl-4-sulfamoylpyrrole-3-carboxylic acid (SPC), which is a potent inhibitor of MBLs. SPC is a remarkable lead compound for clinically useful MBL inhibitors and can potentially provide a considerable benefit to patients receiving treatment for lethal infectious diseases caused by MBL-producing CRE.


2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Garima Bansal ◽  
Rachelle Allen-McFarlane ◽  
Broderick Eribo

The occurrence of carbapenem-resistant (CR) strains of Acinetobacter baumannii is reported to contribute to the severity of several nosocomial infections, especially in critically ill patients in intensive care units. The present study aims to determine the antibiotic susceptibility, clonality, and genetic mechanism of carbapenem resistance in twenty-eight Acinetobacter baumannii isolates from four hospitals in Washington DC. The antibiotic susceptibility of the isolates was determined by VITEK 2 analyses, while PCR was used to examine the presence of antibiotic-resistant genes and mobile genetic elements. Trilocus multiplex-PCR was used along with pulsed-field gel electrophoresis (PFGE) for strain typing and for accessing clonal relationships among the isolates. Antimicrobial susceptibility testing indicated that 46% of the isolates were carbapenem-resistant and possessed MDR and XDR phenotypes. PFGE clustered the 28 isolates into seven clonal (C1–C7) complexes based on >75% similarity cut-off. Thirty-six percent of the isolates belonged to international clone II, while 29% were assigned to Group 4 by trilocus multiplex-PCR. Although the blaOXA-51-like gene was found in all the isolates, only 36% were positive for the blaOXA-23-like gene. PCR analysis also found a metallo-β-lactamase (MBL) gene (blaVIM) in 71% of the isolates. Of the 13 CR isolates, 8 were PCR positive for both blaVIM and blaOXA-23-like genes, while 5 harbored only blaVIM gene. This study revealed the emergence of VIM carbapenemase-producing A. baumannii isolates, which has not been previously reported in the United States.


mSphere ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Masoumeh Douraghi ◽  
Johanna J. Kenyon ◽  
Parisa Aris ◽  
Mahla Asadian ◽  
Sedighe Ghourchian ◽  
...  

ABSTRACT The worldwide distribution of carbapenem-resistant Acinetobacter baumannii (CRAB) has become a global concern, particularly in countries where antibiotic prescription is not tightly regulated. However, knowledge of the genomic aspects of CRAB from many parts of the world is still limited. Here, 50 carbapenem-resistant A. baumannii isolates recovered at a single hospital in Tehran, Iran, during several outbreaks in 2012 and 2013 were found to be resistant to multiple antibiotics. They were examined using PCR mapping and multilocus sequence typing (MLST). All Iranian strains belonged to sequence type 328 in the Institut Pasteur MLST scheme (ST328IP), a single-locus variant of ST81IP, and all Iranian strains contained two carbapenem resistance genes, oxa23 and oxa24. The oxa23 gene is in the transposon Tn2006 in AbaR4, which interrupts the chromosomal comM gene. Phylogenetic analysis using whole-genome sequence (WGS) data for 9 isolates showed that they belonged to the same clade, designated the ST81/ST328 clade, within lineage 2 of global clone 1 (GC1). However, there were two groups that included either KL13 or KL18 at the K locus (KL) for capsular polysaccharide synthesis and either a tet39 or an aadB resistance gene, respectively. The genetic context of the resistance genes was determined, and the oxa24 (OXA-72 variant) and tet39 (tetracycline resistance) genes were each in a pdif module in different plasmids. The aadB gene cassette (which encodes gentamicin, kanamycin, and tobramycin resistance) was harbored by pRAY*, and the aphA6 gene (which encodes amikacin resistance) and sul2 gene (which encodes sulfamethoxazole resistance) were each harbored by a different plasmid. The sequences obtained here will underpin future studies of GC1 CRAB strains from the Middle East region. IMPORTANCE Carbapenem-resistant Acinetobacter baumannii strains are among the most critical antibiotic-resistant bacteria causing hospital-acquired infections and treatment failures. The global spread of two clones has been responsible for the bulk of the resistance, in particular, carbapenem resistance. However, there is a substantial gap in our knowledge of which clones and which specific lineages within each clone are circulating in many parts of the world, including Africa and the Middle East region. This is the first genomic analysis of carbapenem-resistant A. baumannii strains from Iran. All the isolates, from a single hospital, belonged to lineage 2 of global clone 1 (GC1) but fell into two groups distinguished by genes in the locus for capsule biosynthesis. The analysis suggests a potential origin of multiply antibiotic-resistant lineage 2 in the Middle East region and highlights the ongoing evolution of carbapenem-resistant GC1 A. baumannii strains. It will enhance future studies on the local and global GC1 population structure.


mBio ◽  
2018 ◽  
Vol 9 (3) ◽  
Author(s):  
Roberto Adamo ◽  
Immaculada Margarit

ABSTRACT Antibiotics and vaccines have greatly impacted human health in the last century by dramatically reducing the morbidity and mortality associated with infectious diseases. The recent challenge posed by the emergence of multidrug-resistant bacteria could possibly be addressed by novel immune prophylactic and therapeutic approaches. Among the newly threatening pathogens, Klebsiella pneumoniae is particularly worrisome in the nosocomial setting, and its surface polysaccharides are regarded as promising antigen candidates. The majority of Klebsiella carbapenem-resistant strains belong to the sequence type 158 (ST258) lineage, with two main clades expressing capsular polysaccharides CPS1 and CPS2. In a recent article, S. D. Kobayashi and colleagues (mBio 9:e00297-18, 2018, https://doi.org/10.1128/mBio.00297-18) show that CPS2-specific IgGs render ST258 clade 2 bacteria more sensitive to human serum and phagocytic killing. E. Diago-Navarro et al. (mBio 9:e00091-18, 2018, https://doi.org/10.1128/mBio.00091-18) generated two murine monoclonal antibodies recognizing distinct glycotopes of CPS2 that presented functional activity against multiple ST258 strains. These complementary studies represent a step toward the control of this dangerous pathogen.


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