scholarly journals Molecular Epidemiology, Risk Factors and Clinical Outcomes of Carbapenem- and Polymyxin-Resistant Gram-negative Bacterial Infections in Pregnant Women and Infants: A Systematic Review

Author(s):  
John Osei Sekyere ◽  
Melese Abate Reta

AbstractBackgroundCarbapenems and polymyxins are last-resort antibiotics used to treat multidrug-resistant bacterial infections. However, resistance is increasing, even in vulnerable groups such as pregnant women and infants, for whom therapeutic options are limited.MethodUsing a diversity of databases, the literature was searched for studies investigating carbapenem and polymyxin resistance in pregnant women and infants (< 5 years).ResultA final set of 73 manuscripts were used. In almost all countries, carbapenem/polymyxin-resistant Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii infect and/or colonizes neonates and pregnant women, causing periodic outbreaks with very high infant mortalities. Plasmid-borne blaNDM, blaKPC, blaOXA-48, blaIMP,blaVIM and blaGES-5 and ompK35/36 downregulation in clonal strains accelerate the horizontal and vertical transmission of carbapenem resistance in these pathogens. High prevalence of carbapenem/polymyxin resistance and carbapenemases were present in India, China, Pakistan, Thailand, Taiwan, Turkey, Egypt, Italy, USA, South Africa, Algeria, Ghana, and Madagascar. Factors such as antibiotic therapy, prolonged hospitalization, invasive procedures, mother/infant colonization, mechanical ventilation, low-birth weight and preterm state placed infants at high risk of carbapenem/polymyxin-resistant infections. Infant mortalities ranged from 0.2% to 36.8% in different countries.ConclusionUse of polymyxins to treat carbapenem-resistant infections is selecting for resistance to both agents, restricting therapeutic options for infected infants and pregnant women. However, appropriate infection control and antibiotic therapy can contain outbreaks and clear these infections. Antibiotic stewardship, periodic rectal and vaginal screening, and strict infection control practices in neonatal ICUs are necessary to forestall future outbreaks and deaths.HighlightsCarbapenems & polymyxins are last-resort antibiotics used for multidrug-resistant infectionsResistance to these two agents are reported in infants & pregnant womenK. pneumoniae, E. coli, and A. baumannii are the most common pathogensCarbapenem & polymyxin resistance cause outbreaks with high infant mortalitiesAppropriate treatment & infection control can outbreaks & save lives

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.


2015 ◽  
Vol 26 (2) ◽  
pp. 99-106 ◽  
Author(s):  
Caroline Walker

Procalcitonin is a promising biomarker for antibiotic therapy because its levels rise and fall quickly with bacterial infections. A multi-database literature search was reviewed with 3 primary prospective randomized control trials used in further analysis. The results indicated that a procalcitonin-guided antibiotic protocol reduces the number of days a patient has to take antibiotics while having no effect on mortality when compared with control groups. Short-term studies did not show a difference in the intensive care unit length of stay, infection relapse rate, super-infection rate, or multidrug-resistant bacteria rate between the procalcitonin-protocol and control group. Because procalcitonin-guided antibiotic therapy has been shown to reduce the duration of treatment with antibiotics in critically ill patients without worsening the mortality rate or other outcomes, the implementation of a procalcitonin-guided antibiotic therapy should be considered for patients with proven or highly suspected bacterial infections in the intensive care unit.


2015 ◽  
Vol 60 (1) ◽  
pp. 64-74 ◽  
Author(s):  
Daniela Minerdi ◽  
Ivan Zgrablic ◽  
Silvia Castrignanò ◽  
Gianluca Catucci ◽  
Claudio Medana ◽  
...  

ABSTRACTAntimicrobial resistance is a global issue currently resulting in the deaths of hundreds of thousands of people a year worldwide. Data present in the literature illustrate the emergence of many bacterial species that display resistance to known antibiotics;Acinetobacterspp. are a good example of this. We report here thatAcinetobacter radioresistenshas a Baeyer-Villiger monooxygenase (Ar-BVMO) with 100% amino acid sequence identity to the ethionamide monooxygenase of multidrug-resistant (MDR)Acinetobacter baumannii. Both enzymes are only distantly phylogenetically related to other canonical bacterial BVMO proteins. Ar-BVMO not only is capable of oxidizing two anticancer drugs metabolized by human FMO3, danusertib and tozasertib, but also can oxidize other synthetic drugs, such as imipenem. The latter is a member of the carbapenems, a clinically important antibiotic family used in the treatment of MDR bacterial infections. Susceptibility tests performed by the Kirby-Bauer disk diffusion method demonstrate that imipenem-sensitiveEscherichia coliBL21 cells overexpressing Ar-BVMO become resistant to this antibiotic. An agar disk diffusion assay proved that when imipenem reacts with Ar-BVMO, it loses its antibiotic property. Moreover, an NADPH consumption assay with the purified Ar-BVMO demonstrates that this antibiotic is indeed a substrate, and its product is identified by liquid chromatography-mass spectrometry to be a Baeyer-Villiger (BV) oxidation product of the carbonyl moiety of the β-lactam ring. This is the first report of an antibiotic-inactivating BVMO enzyme that, while mediating its usual BV oxidation, also operates by an unprecedented mechanism of carbapenem resistance.


2018 ◽  
Vol 143 (09) ◽  
pp. 625-633 ◽  
Author(s):  
Axel Hamprecht ◽  
Stephan Göttig

AbstractThe increase of multidrug-resistant Gram-negative bacilli (MRGN) is a great threat for both the health system and patients. Challenges of MRGN for physicians are limited therapeutic options, the need of infection control measures and the danger of outbreaks. In this article, the prevalence of MRGN, risk factors, the background and definitions of multidrug-resistant organisms are presented.


2021 ◽  
Vol 15 (9) ◽  
pp. 2280-2281
Author(s):  
Sonia Tahir ◽  
Saadia Chaudhary ◽  
Tahir Naeem

Aim: To figure out the antimicrobial sensitivity effect of multidrug resistant Pseudomonas aeruginosa obtained from several type of clinical specimens. Study setting: Department of Microbiology and Resource laboratory, University of Health Sciences Lahore. Methods: A sum total of 53 isolates of multi-resistant Pseudomonas aeruginosa were selected from Jinnah hospital Lahore during the period of 1st January 2016 to 2nd February 2017. Nutrient agar slants were used for the transportation of resistant strains. In accordance with the CLSI manuals re-confirmation and processing of the strains were accomplished. The sub culturing and incubation was done on culture media such as MacConkey and blood agar at room temperature for 1 day. Standard confirmation of isolates under went by the graded morphological, cultural and biochemical techniques. In order to achieve this, Gram staining, culture media such as blood, oxidase test, motility test were executed. Results: The resistance pattern of Pseudomonas aeruginosa against antibiotics was as follows: Meropenem 53(100%), 51(96%) to piperacillin–tazobactam, 49(92%) to ceftazidime, 43(81%) to amikacin, 41(77%) showed resistance to aztreonam, 48(91%) to quinolones as shown in figure. Almost all the Pseudomonas aeruginosa were resistant to aztreonam except for 23% (n=12 isolates). Colistin was predominant as the major strength of treatment for Pseudomonas aeruginosa with sensitivity of 48(91%). Keywords: Disk-diffusion, Carbapenem, McFarland.


mSystems ◽  
2020 ◽  
Vol 5 (3) ◽  
Author(s):  
John Osei Sekyere ◽  
Nontuthuko E. Maningi ◽  
Lesedi Modipane ◽  
Nontombi Marylucy Mbelle

ABSTRACT Extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae are critical-priority pathogens that cause substantial fatalities. With the emergence of mobile mcr genes mediating resistance to colistin in Enterobacteriaceae, clinicians are now left with few therapeutic options. Eleven clinical Enterobacteriaceae strains with resistance to cephems and/or colistin were genomically analyzed to determine their resistomes, mobilomes, and evolutionary relationships to global strains. The global phylogenomics of mcr genes and mcr-9.1-bearing genomes were further analyzed. Ten isolates were ESBL positive. The isolates were multidrug resistant and phylogenetically related to global clones but distant from local strains. Multiple resistance genes, including blaCTX-M-15 blaTEM-1, and mcr-9.1, were found in single isolates; ISEc9, IS19, and Tn3 transposons bracketed blaCTX-M-15 and blaTEM-1. Common plasmid types included IncF, IncH, and ColRNAI. mcr-9 was of close sequence identity to mcr-3, mcr-5, mcr-7, mcr-8, and mcr-10. Genomes bearing mcr-9.1 clustered into six main phyletic groups (A to F), with those of this study belonging to clade B. Enterobacter species and Salmonella species are the main hosts of mcr-9.1 globally, although diverse promiscuous plasmids disseminate mcr-9.1 across different bacterial species. Emergence of mcr-9.1 in ESBL-producing Enterobacteriaceae in South Africa is worrying, due to the restricted therapeutic options. Intensive One Health molecular surveillance might discover other mcr alleles and inform infection management and antibiotic choices. IMPORTANCE Colistin is currently the last-resort antibiotic for difficult-to-treat bacterial infections. However, colistin resistance genes that can move from bacteria to bacteria have emerged, threatening the safe treatment of many bacterial infections. One of these genes, mcr-9.1, has emerged in South Africa in bacteria that are multidrug resistant, further limiting treatment options for clinicians. In this work, we show that this new gene is disseminating worldwide through Enterobacter and Salmonella species through multiple plasmids. This worrying observation requires urgent action to prevent further escalation of this gene in South Africa and Africa.


2021 ◽  
Vol 9 (5) ◽  
pp. 1158-1164
Author(s):  
Sahibi Mohamed Elmehdi ◽  
◽  
Yafi Imane ◽  
Mahrouch El Mehdi ◽  
Elgueouatri Mehdi ◽  
...  

The nosocomial bacterial infection being one of the main causes of morbidity and mortality in burn patients, our work aimed on describing the nosocomial bacterial infections in order to establish the bacteriological profile to adapt the antibiotic therapy to our service. This is a retrospective study of 502 bacteriological samples taken from 65 patients hospitalized in the Resuscitation of burns of the plastic surgery department of the CHU Mohamed VI of Marrakech, over a period of 3 years, from January 1, 2016 to December 31, 2018. For this which is characteristic of bacterial infections, the infected sites were mainly the skin (50.1%) and blood (37.7%). The main germs were: Coagulase Negative Staphylococcus (32.1%), AcinetobacterBamannii (13.8%) Staphylococcus Aures (8.45%) AND Pseudomonas Aeruginosa (8.2%). Staphylococci were metabolic-resistant in 16.6% of cases Pseudomonas and Acinetobacter were multidrug resistant (60%). Establishing the bacterial ecology of the service, allowed us to set the right rules for prescribing antibiotic therapy, which was a function of the infected site, the type of germ, its sensitivity, the molecule used and the particular pharmacokinetics in the burn patient.


2020 ◽  
Vol 71 (Supplement_4) ◽  
pp. S372-S378
Author(s):  
Zhiyong Zong ◽  
Anhua Wu ◽  
Bijie Hu

Abstract More than 3 decades have passed since infection control was implemented nationwide in China in 1986. A comprehensive set of regulations and guidelines has been developed, and almost all hospitals have established infection control teams. However, compliance is variable and is usually suboptimal. The incidence of certain multidrug-resistant organisms (MDROs), including carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Klebsiella pneumoniae (CRKP), is increasing, and associated infections are mainly hospital-acquired in China. Carbapenem-resistant Pseudomonas aeruginosa has remained relatively stable, whereas methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterobacter faecium have been decreasing. The spread of CRAB and CRKP in China is largely mediated by dominant high-risk lineages, namely, clonal complex 92 for CRAB and sequence type 11 for CRKP. However, challenges owing to MDROs bring opportunities for rethinking, taking coordinated action, building capacity, changing behavior, and performing studies that reflect everyday situations in the Chinese healthcare system.


mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Sean Conlan ◽  
Anna F. Lau ◽  
Clay Deming ◽  
Christine D. Spalding ◽  
ShihQueen Lee-Lin ◽  
...  

ABSTRACT Antibiotics, which are used both to prevent and to treat infections, are a mainstay therapy for lifesaving procedures such as transplantation. For this reason, and many others, increased antibiotic resistance among human-associated pathogens, such as the carbapenem-resistant Enterobacteriaceae species, is of grave concern. In this study, we report on a hematopoietic stem cell transplant recipient in whom cultures detected the emergence of carbapenem resistance and spread across five strains of bacteria that persisted for over a year. Carbapenem resistance in Citrobacter freundii, Enterobacter cloacae, Klebsiella aerogenes, and Klebsiella pneumoniae was linked to a pair of plasmids, each carrying the Klebsiella pneumoniae carbapenemase gene (blaKPC). Surveillance cultures identified a carbapenem-susceptible strain of Citrobacter freundii that may have become resistant through horizontal gene transfer of these plasmids. Selection of a multidrug-resistant Klebsiella pneumoniae strain was also detected following combination antibiotic therapy. Here we report a plasmid carrying the blaKPC gene with broad host range that poses the additional threat of spreading to endogenous members of the human gut microbiome. IMPORTANCE Antibiotic-resistant bacteria are a serious threat to medically fragile patient populations. The spread of antibiotic resistance through plasmid-mediated mechanisms is of grave concern as it can lead to the conversion of endogenous patient-associated strains to difficult-to-treat pathogens.


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