PHP20 - EUROPE-WIDE SPREAD OF CARBAPENEM-RESISTANT BACTERIA: EPIDEMIOLOGY AND DISEASE BURDEN

Antibiotic resistance is a public health threat of the utmost importance, especially when it comes to children: according to WHO data, infections caused by multidrug resistant bacteria produce 700,000 deaths across all ages, of which around 200,000 are newborns. This surging issue has multipronged roots that are specific to the pediatric age. For instance, the problematic overuse and misuse of antibiotics (for wrong diagnoses and indications, or at wrong dosage) is also fueled by the lack of pediatric-specific data and trials. The ever-evolving nature of this age group also poses another issue: the partly age-dependent changes of a developing system of cytochromes determine a rather diverse population in terms of biochemical characteristics and pharmacokinetics profiles, hard to easily codify in an age- or weight-dependent dosage. The pediatric population is also penalized by the contraindications of tetracyclines and fluoroquinolones, and by congenital malformations which often require repeated hospitalizations and pharmacological and surgical treatments from a very young age. Emerging threats for the pediatric age are MRSA, VRSA, ESBL-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae and the alarming colistin resistance. Urgent actions need to be taken in order to step back from a now likely post-antibiotic era, where simple infections might cause infant death once again.

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Prevalence of Antibiotic-Resistant Bacteria ESKAPE among Healthy People Estimated by Monitoring of Municipal Wastewater

Antibiotics ◽

10.3390/antibiotics10050495 ◽

2021 ◽

Vol 10 (5) ◽

pp. 495

Author(s):

Masateru Nishiyama ◽

Susan Praise ◽

Keiichi Tsurumaki ◽

Hiroaki Baba ◽

Hajime Kanamori ◽

...

Keyword(s):

Antibiotic Resistance ◽

General Population ◽

Municipal Wastewater ◽

Treatment Plant ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Municipal Wastewater Treatment ◽

Antibiotic Resistant ◽

Carbapenem Resistant ◽

Wastewater Samples

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.

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Neonates with Maternal Colonization of Carbapenemase-Producing, Carbapenem-Resistant Enterobacteriaceae: A Mini-Review and a Suggested Guide for Preventing Neonatal Infection

Children ◽

10.3390/children8050399 ◽

2021 ◽

Vol 8 (5) ◽

pp. 399

Author(s):

Judy Seesahai ◽

Paige Terrien Church ◽

Elizabeth Asztalos ◽

Melanee Eng-Chong ◽

Jo Arbus ◽

...

Keyword(s):

Neonatal Intensive Care ◽

Neonatal Infection ◽

Control Measures ◽

Resistant Bacteria ◽

Negative Consequences ◽

Duration Of Treatment ◽

Contact Precautions ◽

Carbapenem Resistant ◽

Carbapenem Resistant Enterobacteriaceae

Carbapenemase-producing, carbapenem-resistant Enterobacteriaceae (CP-CRE) are highly drug-resistant Gram-negative bacteria. They include New Delhi metallo-ß-lactamase (NDM)-producing carbapenemase (50.4% of all species in Ontario). Antibiotic challenges for resistant bacteria in neonates pose challenges of unknown dosing and side effects. We report two antenatally diagnosed CP-CRE colonization scenarios with the NDM 1 gene. The case involves extreme preterm twins who had worsening respiratory distress at birth requiring ventilator support, with the first twin also having cardiovascular instability. They were screened for CP-CRE, and a polymyxin antibiotic commenced. In the delivery room, neonatal intensive care unit (NICU) and the follow-up clinic, in collaboration with the interdisciplinary group, contact precautions and isolation procedures were instituted. None of the infants exhibited infection with CP-CRE. Consolidating knowledge with regard to CP-CRE and modifying human behavior associated with its spread can mitigate potential negative consequences. This relates to now and later, when travel and prolific human to human contact resumes, from endemic countries, after the current COVID-19 pandemic. Standardized efforts to curb the acquisition of this infection would be judicious given the challenges of treatment and continued emerging antibiotic resistance. Simple infection control measures involving contact precautions, staff education and parental cohorting can be useful and cost-effective in preventing transmission. Attention to NICU specific measures, including screening of at-risk mothers (invitro fertilization conception) and their probands, careful handling of breastmilk, judicious antibiotic choice and duration of treatment, is warranted. What does this study add? CP-CRE is a nosocomial infection with increasing incidence globally, and a serious threat to public health, making it likely that these cases will present with greater frequency to the NICU team. Only a few similar cases have been reported in the neonatal literature. Current published guidelines provide a framework for general hospital management. Still, they are not specific to the NICU experience and the need to manage the parents’ exposure and the infants. This article provides a holistic framework for managing confirmed or suspected cases of CP-CRE from the antenatal care through the NICU and into the follow-up clinic targeted at preventing or containing the spread of CP-CRE.

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Aminoglycoside antibiotic resistance conferred by Hpa2 of MDR Acinetobacter baumannii: an unusual adaptation of a common histone acetyltransferase

Biochemical Journal ◽

10.1042/bcj20180791 ◽

2019 ◽

Vol 476 (5) ◽

pp. 795-808 ◽

Cited By ~ 2

Author(s):

Jyoti Singh Tomar ◽

Rama Krishna Peddinti ◽

Ramakrishna V. Hosur

Keyword(s):

Acinetobacter Baumannii ◽

Histone Acetyltransferase ◽

Hydrophobic Interactions ◽

Aminoglycoside Antibiotic ◽

Aminoglycoside Antibiotics ◽

Titration Calorimetry ◽

Resistant Bacteria ◽

Antibiotic Resistant ◽

Carbapenem Resistant ◽

Eskape Pathogens

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.

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An overview of carbapenem, its resistance and therapeutic options for infections caused by carbapenem resistant bacteria

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20203635 ◽

2020 ◽

Vol 9 (9) ◽

pp. 1454

Author(s):

Hari P. Nepal ◽

Rama Paudel

Keyword(s):

Bacterial Infections ◽

Carbapenem Resistance ◽

Therapeutic Options ◽

Resistant Bacteria ◽

Gram Negative Bacteria ◽

Beta Lactam ◽

Gram Negative ◽

Penicillin Binding Proteins ◽

Carbapenem Resistant ◽

The World

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.

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Screening for carbapenem-resistant bacteria

The Lancet Infectious Diseases ◽

10.1016/s1473-3099(05)70223-1 ◽

2005 ◽

Vol 5 (10) ◽

pp. 597-598 ◽

Cited By ~ 4

Author(s):

James S Soothill ◽

Paul E Lock

Keyword(s):

Resistant Bacteria ◽

Carbapenem Resistant

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Emerging carbapenem resistance in ESKAPE organisms in sub-Saharan Africa and the way forward

German Journal of Microbiology - Special Issue: Existence Battle: Viruses vs. Creatures ◽

10.51585/gjm.2021.002 ◽

2021 ◽

Vol 1 (1) ◽

pp. 3-6

Author(s):

John Njeru

Keyword(s):

Public Health ◽

Carbapenem Resistance ◽

Developed Countries ◽

Sub Saharan Africa ◽

Resistant Bacteria ◽

Carbapenem Resistant ◽

Public Health Threat ◽

Enterobacter Species ◽

Significant Public Health ◽

Sub Saharan

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

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Molecular characteristics of carbapenem-resistant Acinetobacter spp. from clinical infection samples and fecal survey samples in Southern China

BMC Infectious Diseases ◽

10.1186/s12879-019-4423-3 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 5

Author(s):

Si Li ◽

Xiaonv Duan ◽

Yuan Peng ◽

Yongyu Rui

Keyword(s):

Efflux Pump ◽

Southern China ◽

Variable Region ◽

Carbapenem Resistance ◽

Resistant Bacteria ◽

Molecular Characteristics ◽

Clinical Infection ◽

High Genetic Diversity ◽

Carbapenem Resistant ◽

Opportunistic Bacteria

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.

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A public health concern: emergence of carbapenem-resistant Klebsiella pneumoniae in a public transportation environment

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkaa260 ◽

2020 ◽

Vol 75 (10) ◽

pp. 2769-2772

Author(s):

Tingting Cao ◽

Yuanyuan Liu ◽

Yiming Li ◽

Yang Wang ◽

Zhangqi Shen ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Public Transportation ◽

Genetic Relationships ◽

Brain Heart Infusion ◽

Health Concern ◽

Resistant Bacteria ◽

Carbapenem Resistant ◽

Broth Microdilution Method ◽

Carbapenem Resistant Enterobacteriaceae ◽

Beijing Subway

Abstract Objectives This study was designed to understand the prevalence of antibiotic-resistant bacteria in the Beijing subway environment and the potential transmission of carbapenem-resistant Enterobacteriaceae in a public transportation environment. Methods Carbapenem-resistant isolates were selected on brain heart infusion agar supplemented with meropenem (0.5 mg/L) and antimicrobial susceptibility testing was conducted using the broth microdilution method. WGS analyses were conducted for 11 Klebsiella pneumoniae isolates to identify resistance genes. The genetic relationships among the isolates were evaluated by MLST and PFGE. Results We identified 11 carbapenem-resistant K. pneumoniae isolates from the Beijing subway environment. WGS revealed three STs among the 11 isolates, with 9 isolates classified as ST726 and containing a blaNDM-5-carrying IncX3 plasmid. The genetic environment of blaNDM-5 was very similar to that observed in other blaNDM-5-containing clinical isolates. Conclusions The presence of carbapenem-resistant Enterobacteriaceae in a public transportation environment is concerning and indicates that regular antimicrobial resistance surveillance is urgent and necessary.

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