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1.
Front Public Health ; 11: 1244357, 2023.
Article in English | MEDLINE | ID: mdl-38074724

ABSTRACT

Introduction: Although pneumococcal conjugate vaccines (PCV) have been effective in reducing the burden of Streptococcus pneumoniae infections, there is a paucity of data on the relationship with antimicrobial resistance (AMR) trends in the Arabian Gulf region. This study was carried out to assess S. pneumoniae resistance trends in the United Arab Emirates (UAE) where PCV-13 vaccination was introduced in 2011. Methods: Retrospective analysis of S. pneumoniae demographic and microbiological data collected as part of the national AMR surveillance program from 2010 to 2021 was carried out. A survey of reporting sites and hand searching of annual reports of local health authorities was carried out to identify data on S. pneumoniae serotypes as this is not included in the AMR surveillance database. Results: From 2010 to 2021, 11,242 non-duplicate S. pneumoniae isolates were reported, increasing from 324 in 2010 to 1,115 in 2021. Factoring in annual increment in the number of surveillance sites, the number of isolates per site showed an upward trajectory from 2015 to 2018 and declined in 2020 with the onset of the pandemic. The majority of isolates (n/N = 5,751/11,242; 51.2%) were from respiratory tract specimens with 44.5% (n/N = 2,557/5,751) being nasal colonizers. Up to 11.9% (n/N = 1,337/11,242) were invasive pneumococcal disease (IPD) isolates obtained from sterile site specimens including blood (n = 1,262), cerebrospinal (n = 52), pleural (n = 19) and joint (n = 4) fluid; and were predominantly from pediatric patients. The downward trend for amoxicillin and for penicillin G at the non-meningitis and meningitis as well as oral penicillin breakpoints was statistically significant. In contrast, increasing trends of resistance were seen for levofloxacin, moxifloxacin, trimethoprim/sulfamethoxazole and erythromycin. IPD and non-IPD isolates showed similar demographic and AMR trends. None of the surveillance sites carried out S. pneumoniae serotyping and handsearching of annual reports did not yield this information. Conclusion: The increasing trend of pneumococcal disease and AMR with emergence of isolates with MDR phenotype despite is of concern. In the absence of S. pneumoniae serotyping the role of non-vaccine serotypes in driving this pattern remains unknown. There is an urgent need for serotype, genomic and AMR surveillance of S. pneumoniae isolates in the UAE.


Subject(s)
Pneumococcal Infections , Streptococcus pneumoniae , Child , Humans , Anti-Bacterial Agents/pharmacology , Retrospective Studies , United Arab Emirates/epidemiology , Drug Resistance, Bacterial , Pneumococcal Vaccines , Pneumococcal Infections/drug therapy , Pneumococcal Infections/epidemiology , Pneumococcal Infections/microbiology
2.
Front Public Health ; 11: 1244482, 2023.
Article in English | MEDLINE | ID: mdl-38145078

ABSTRACT

Background: Carbapenem-resistant Enterobacterales (CRE) are spreading in the United Arab Emirates (UAE) where their dissemination is facilitated by international travel, trade, and tourism. The objective of this study is to describe the longitudinal changes of CRE as reported by the national AMR surveillance system of the UAE. Methods: In this study, we retrospectively describe CRE isolated from 317 surveillance sites, including 87 hospitals and 230 centers/clinics from 2010 to 2021. The associated clinical, demographic, and microbiological characteristics are presented by relying on the UAE national AMR surveillance program. Data was analyzed using WHONET microbiology laboratory database software (http://www.whonet.org). Results: A total of 14,593 carbapenem resistant Enterobacterales were analyzed, of which 48.1% were carbapenem resistant Klebsiella pneumoniae (CRKp), 25.1% carbapenem resistant Escherichia coli (CREc), and 26.8% represented 72 other carbapenem resistant species. Carbapenem resistant strains were mostly associated with adults and isolated from urine samples (36.9% of CRKp and 66.6% of CREc) followed by respiratory samples (26.95% for CRKp) and soft tissue samples (19.5% for CRKp). Over the studied period carbapenem resistance rates remained high, especially in K. pneumoniae, and in 2021 were equivalent to 67.6% for imipenem, 76.2% for meropenem, and 91.6% for ertapenem. Nevertheless, there was a statistically significant decreasing trend for imipenem and meropenem resistance in Klebsiella species (p < 0.01) while the decrease in ertapenem resistance was non-significant. Concerning E. coli, there was a statistically significant decreasing trend for meropenem and imipenem resistance over the 12 years, while ertapenem resistance increased significantly with 83.8% of E. coli exhibiting ertapenem resistance in 2021. Resistance rates to ceftazidime and cefotaxime remained higher than 90% (in 2021) for CRKp and cefotaxime rates increased to 90.5% in 2021 for CREc. Starting 2014, resistance to colistin and tigecycline was observed in carbapenem resistant Enterobacterales. CRE were associated with a higher mortality (RR: 6.3), admission to ICU (RR 3.9), and increased length of stay (LOS; 10 excess inpatient days per CRE case). Conclusion: This study supports the need to monitor CRE in the UAE and draws attention to the significant increase of ertapenem resistance in E. coli. Future surveillance analysis should include a genetic description of carbapenem resistance to provide new strategies.


Subject(s)
Anti-Bacterial Agents , Escherichia coli , Humans , Adult , Anti-Bacterial Agents/pharmacology , Meropenem , Ertapenem , Retrospective Studies , Escherichia coli/genetics , United Arab Emirates/epidemiology , Carbapenems/pharmacology , Imipenem , Klebsiella pneumoniae/genetics , Cefotaxime
3.
Front Public Health ; 11: 1244351, 2023.
Article in English | MEDLINE | ID: mdl-38145065

ABSTRACT

Introduction: Methicillin resistant Staphylococcus aureus (MRSA) is a major contributor to the global burden of antimicrobial resistance (AMR). As MRSA continues to evolve, the need for continued surveillance to evaluate trends remains crucial. This study was carried out to assess MRSA trends in the United Arab Emirates (UAE) based on analysis of data from the national AMR surveillance program. Methods: We carried out a 12-year (2010-2021) retrospective analysis of MRSA demographic and microbiological data collected as part of the UAE national AMR surveillance program. Participating centers from across the country routinely submit AMR surveillance data collected by trained personnel to the National AMR Surveillance Committee, where data is analyzed using a unified WHONET platform. Data on non-duplicate isolates associated with clinical infections were obtained and included in the analysis. Results: A total of 29,414 non-duplicate MRSA isolates associated with clinical infections were reported between 2010 and 2021 (2010: n = 259; 2021: n = 4,996). MRSA represented 26.4% of all S. aureus (n = 111,623) isolates identified during the study period. In 2010, among the S. aureus isolates with reported oxacillin testing, 21.9% (n/N = 259/1,181) were identified as MRSA and this showed an increase to 33.5% (n/N = 4,996/14,925) in 2021. Although there was variation in the distribution of MRSA across the seven emirates of the country, most had an upward trend. Patient demographics reflected a male preponderance, with most being adults and from the outpatient setting. Isolates were mostly from skin and soft tissue infection specimens (72.5%; n/N = 21,335/29,414). Among the inpatients (N = 8,282), a total of 3,313 MRSA isolates were from specimens obtained ≤ 48 h after admission indicative of community acquired infection. Increasing resistance trends were observed for most antibiotics including ciprofloxacin, levofloxacin, moxifloxacin, erythromycin, gentamicin, trimethoprim-sulfamethoxazole, and quinupristin/dalfopristin. Low levels of resistance (0.0-0.8%) were sustained for linezolid except for 2015, 2016, and 2017 with 2.5, 2.6, and 2.9%, respectively. No confirmed vancomycin resistance was reported. Conclusion: The increasing trend of MRSA isolates associated with clinical infections in the hospital and community settings is a concern. Continued monitoring including incorporation of genomic surveillance and infection control measures are recommended to stem the dissemination.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Adult , Male , Humans , Methicillin-Resistant Staphylococcus aureus/genetics , Staphylococcus aureus/genetics , Retrospective Studies , United Arab Emirates/epidemiology , Staphylococcal Infections/epidemiology , Staphylococcal Infections/microbiology
4.
Front Public Health ; 11: 1245131, 2023.
Article in English | MEDLINE | ID: mdl-38239785

ABSTRACT

Introduction: Acinetobacter spp., in particular A. baumannii, are opportunistic pathogens linked to nosocomial pneumonia (particularly ventilator-associated pneumonia), central-line catheter-associated blood stream infections, meningitis, urinary tract infections, surgical-site infections, and other types of wound infections. A. baumannii is able to acquire or upregulate various resistance determinants, making it frequently multidrug-resistant, and contributing to increased mortality and morbidity. Data on the epidemiology, levels, and trends of antimicrobial resistance of Acinetobacter spp. in clinical settings is scarce in the Gulf Cooperation Council (GCC) and Middle East and North Africa (MENA) regions. Methods: A retrospective 12-year analysis of 17,564 non-duplicate diagnostic Acinetobacter spp. isolates from the United Arab Emirates (UAE) was conducted. Data was generated at 317 surveillance sites by routine patient care during 2010-2021, collected by trained personnel and reported by participating surveillance sites to the UAE National AMR Surveillance program. Data analysis was conducted with WHONET. Results: Species belonging to the A. calcoaceticus-baumannii complex were mostly reported (86.7%). They were most commonly isolated from urine (32.9%), sputum (29.0%), and soft tissue (25.1%). Resistance trends to antibiotics from different classes during the surveillance period showed a decreasing trend. Specifically, there was a significant decrease in resistance to imipenem, meropenem, and amikacin. Resistance was lowest among Acinetobacter species to both colistin and tigecycline. The percentages of multidrug-resistant (MDR) and possibly extensively drug-resistant (XDR) isolates was reduced by almost half between the beginning of the study in 2010 and its culmination in 2021. Carbapenem-resistant Acinetobacter spp. (CRAB) was associated with a higher mortality (RR: 5.7), a higher admission to ICU (RR 3.3), and an increased length of stay (LOS; 13 excess inpatient days per CRAB case), as compared to Carbapenem-susceptible Acinetobacter spp. Conclusion: Carbapenem-resistant Acinetobacter spp. are associated with poorer clinical outcomes, and higher associated costs, as compared to carbapenem-susceptible Acinetobacter spp. A decreasing trend of MDR Acinetobacter spp., as well as resistance to all antibiotic classes under surveillance was observed during 2010 to 2021. Further studies are needed to explore the reasons and underlying factors leading to this remarkable decrease of resistance over time.


Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Retrospective Studies , United Arab Emirates/epidemiology , Acinetobacter Infections/drug therapy , Acinetobacter Infections/epidemiology , Drug Resistance, Bacterial , Carbapenems
5.
F1000Res ; 12: 92, 2023.
Article in English | MEDLINE | ID: mdl-38915769

ABSTRACT

The ongoing spread of antimicrobial resistance has complicated the treatment of bacterial hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). Gram-negative pathogens, especially those with multidrug-resistant profiles, including Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Pseudomonas aeruginosa, and Acinetobacter spp., are important culprits in this type of infections. Understanding the determinants of resistance in pathogens causing pneumonia is ultimately stressing, especially in the shadows of the COVID-19 pandemic, when bacterial lung infections are considered a top priority that has become urgent to revise. Globally, the increasing prevalence of these pathogens in respiratory samples represents a significant infection challenge, with major limitations of treatment options and poor clinical outcomes. This review will focus on the epidemiology of HAP and VAP and will present the roles and the antimicrobial resistance patterns of implicated multidrug-resistant (MDR) Gram-negative pathogens like carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA), carbapenem-resistant Enterobacterales (CRE), as well as colistin-resistant Gram-negative pathogens and extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales. While emerging from the COVID-19 pandemic, perspectives and conclusions are drawn from findings of HAP and VAP caused by MDR Gram-negative bacteria in patients with COVID-19.

6.
Yale J Biol Med ; 95(4): 507-515, 2022 12.
Article in English | MEDLINE | ID: mdl-36568831

ABSTRACT

Worldwide, Pseudomonas aeruginosa remains a leading nosocomial pathogen that is difficult to treat and constitutes a challenging menace to healthcare systems. P. aeruginosa shows increased and alarming resistance to carbapenems, long acknowledged as last-resort antibiotics for treatment of resistant infections. Varied and recalcitrant pathways of resistance to carbapenems can simultaneously occur in P. aeruginosa, including the production of carbapenemases, broadest spectrum types of ß-lactamases that hydrolyze virtually almost all ß-lactams, including carbapenems. The organism can produce chromosomal, plasmid-encoded, and integron- or transposon-mediated carbapenemases from different molecular classes. These include Ambler class A (KPC and some types of GES enzymes), class B (different metallo-ß-lactamases such as IMP, VIM, and NDM), and class D (oxacillinases with carbapenem-hydrolyzing capacity like OXA-198) enzymes. Additionally, derepression of chromosomal AmpC cephalosporinases in P. aeruginosa contributes to carbapenem resistance in the presence of other concomitant mechanisms such as impermeability or efflux overexpression. Epidemiologic and molecular evidence of carbapenemases in P. aeruginosa has been long accumulating, and reports of their existence in different geographical areas of the world currently exist. Such reports are continuously being updated and reveal emerging varieties of carbapenemases and/or new genetic environments. This review summarizes carbapenemases of importance in P. aeruginosa, highlights their genetic profile, and presents current knowledge about their global epidemiology.


Subject(s)
Genetic Profile , Pseudomonas aeruginosa , Humans , Pseudomonas aeruginosa/genetics , beta-Lactamases/genetics , beta-Lactamases/metabolism , Anti-Bacterial Agents/pharmacology , Carbapenems/pharmacology , Carbapenems/metabolism , Microbial Sensitivity Tests
7.
Metabolites ; 12(11)2022 Nov 01.
Article in English | MEDLINE | ID: mdl-36355134

ABSTRACT

Peptide-hormones, including pancreatic peptide-YY(PYY), glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), insulin, and leptin function as satiety signals, while ghrelin promotes hunger. These hormones are also involved in glucose homeostasis and body-weight regulation. The aim of this cross-sectional analysis was to examine the association of these peptide-hormones with obesity-markers, insulin-resistance, and dyslipidemia (total-cholesterol (TC), low-density-lipoprotein-cholesterol (LDL-C), high-density-lipoprotein-cholesterol (HDL-C), triglyceride (TG)). Sixteen-obese (OB) adults and 21 normal-weight (NW) age-and gender-matched counterparts were recruited. OB-participants showed significantly higher levels of leptin, insulin, Homeostatic-Model Assessment of Insulin Resistance (HOMA-IR), and TG. NW participants had significantly higher levels of ghrelin. GLP-1 was positively correlated with insulin, HOMA-IR, and obesity-markers except percent body fat. Leptin was positively correlated with all markers (except glucose and dyslipidemia). PYY was positively correlated with BMI, insulin and HOMA-IR. Ghrelin was inversely correlated with all of the markers except glucose, TC, and LDL-C. In the regression analysis model, leptin was positively associated with obesity markers and insulin resistance. Our results indicate a significant difference in peptide hormones among OB and NW Lebanese individuals. Since there is controversial evidence regarding body-weight and peptide-hormones in the literature, this study highlights a step forward towards finding ethnic based strategies to treat obesity and its consequences.

8.
Front Cell Infect Microbiol ; 12: 823626, 2022.
Article in English | MEDLINE | ID: mdl-35372126

ABSTRACT

The serious challenge of antimicrobial resistance continues to threaten public health and lingers in the era of the coronavirus disease 2019 (COVID-19), declared pandemic by the World Health Organization. While the pandemic has triggered the importance of infection control practices and preventive measures such as physical distancing, hand hygiene, travel reduction and quarantine, the ongoing alarm of antimicrobial resistance seems to accompany the pandemic too. Antimicrobial resistance has been fostered during COVID-19, possibly due to high rate of empirical antibiotic utilization in COVID-19 patients, increased use of biocides, and the disruption of proper healthcare for other conditions. Specifically, carbapenemase-producing Gram-negative bacteria have shown to cause secondary bacterial infections in patients hospitalized for COVID-19. Clinical and microbiological evidence of such infections is accumulating in different parts of the world. With the resilient nature of carbapenemases, their association with mortality, and the limited treatment options available, concerns regarding this group of antibiotic-hydrolyzing enzymes during the pandemic are expected to upsurge. While the additional burden carbapenemases exert on healthcare is worrisome, it remains hidden or abandoned among the various health consequences of the pandemic. The purpose of this minireview is to shed a light on carbapenemase-associated infections during such unprecedented time of COVID-19. A focused insight shall be made into carbapenemases, their implications for COVID-19 patients, and the features and consequences of co-infection, with a review of available evidence from pertinent literature. The importance of increased surveillance for carbapenemase-producers and optimizing their management in relation to the pandemic, shall be addressed as well.


Subject(s)
COVID-19 , Bacterial Proteins , Humans , Pandemics , beta-Lactamases
10.
Membranes (Basel) ; 10(8)2020 Aug 08.
Article in English | MEDLINE | ID: mdl-32784516

ABSTRACT

Following their initial discovery in the 1940s, polymyxin antibiotics fell into disfavor due to their potential clinical toxicity, especially nephrotoxicity. However, the dry antibiotic development pipeline, together with the rising global prevalence of infections caused by multidrug-resistant (MDR) Gram-negative bacteria have both rejuvenated clinical interest in these polypeptide antibiotics. Parallel to the revival of their use, investigations into the mechanisms of action and resistance to polymyxins have intensified. With an initial known effect on biological membranes, research has uncovered the detailed molecular and chemical interactions that polymyxins have with Gram-negative outer membranes and lipopolysaccharide structure. In addition, genetic and epidemiological studies have revealed the basis of resistance to these agents. Nowadays, resistance to polymyxins in MDR Gram-negative pathogens is well elucidated, with chromosomal as well as plasmid-encoded, transferrable pathways. The aims of the current review are to highlight the important chemical, microbiological, and pharmacological properties of polymyxins, to discuss their mechanistic effects on bacterial membranes, and to revise the current knowledge about Gram-negative acquired resistance to these agents. Finally, recent research, directed towards new perspectives for improving these old agents utilized in the 21st century, to combat drug-resistant pathogens, is summarized.

11.
Nutrients ; 12(6)2020 Jun 09.
Article in English | MEDLINE | ID: mdl-32526930

ABSTRACT

The composition of human breast milk is affected by several factors, including genetics, geographic location and maternal nutrition. This study investigated the human milk oligosaccharides (HMOs) of breastfeeding mothers living in Dubai and their relations with the milk microbiota. A total of 30 breast milk samples were collected from healthy Emirati and UAE-expatriates at Latifa Hospital. HMO profiling was performed using UHPLC-MS. Microbiota profiles were determined by sequencing amplicons of the V3-V4 region of the 16S rRNA gene. HMO concentrations were significantly higher in Emirati, and dropped with the lactation period in both groups of mothers. The Le (a-b+)-secretor (Le+Se+) type was the most abundant in Dubai mothers (60%), followed by the Le(a-b-)-secretor (Le-Se+) type (23%). Bifidobacterium and Lactobacillus were considerably lower in Dubai-based mothers, while Pseudomonas and Delftia (Hydrogenophaga) were detected at a higher abundance compared to mothers from other countries. Atopobium was correlated with sialyl-lacto-N-tetraose c, Leptotrichia and Veillonella were correlated with 6'-sialyl-lactose, and Porphyromonas was correlated with lacto-N-hexaose. The study highlights the HMO profiles of breastfeeding mothers in Dubai and reveals few correlations with milk microbial composition. Targeted genomic analyses may help in determining whether these differences are due to genetic variations or to sociocultural and environmental factors.


Subject(s)
Microbiota/physiology , Milk, Human/chemistry , Milk, Human/microbiology , Oligosaccharides/analysis , Adult , Bacteria/classification , Bacteria/genetics , Breast Feeding , Female , Humans , Lactation/physiology , RNA, Ribosomal, 16S/genetics , United Arab Emirates
12.
Antibiotics (Basel) ; 9(4)2020 Apr 16.
Article in English | MEDLINE | ID: mdl-32316342

ABSTRACT

Carbapenemases are ß-lactamases belonging to different Ambler classes (A, B, D) and can be encoded by both chromosomal and plasmid-mediated genes. These enzymes represent the most potent ß-lactamases, which hydrolyze a broad variety of ß-lactams, including carbapenems, cephalosporins, penicillin, and aztreonam. The major issues associated with carbapenemase production are clinical due to compromising the activity of the last resort antibiotics used for treating serious infections, and epidemiological due to their dissemination into various bacteria across almost all geographic regions. Carbapenemase-producing Enterobacteriaceae have received more attention upon their first report in the early 1990s. Currently, there is increased awareness of the impact of nonfermenting bacteria, such as Acinetobacter baumannii and Pseudomonas aeruginosa, as well as other Gram-negative bacteria that are carbapenemase-producers. Outside the scope of clinical importance, carbapenemases are also detected in bacteria from environmental and zoonotic niches, which raises greater concerns over their prevalence, and the need for public health measures to control consequences of their propagation. The aims of the current review are to define and categorize the different families of carbapenemases, and to overview the main lines of their spread across different bacterial groups.

13.
Antibiotics (Basel) ; 9(3)2020 Mar 12.
Article in English | MEDLINE | ID: mdl-32178356

ABSTRACT

Being a multidrug-resistant and an invasive pathogen, Acinetobacter baumannii is one of the major causes of nosocomial infections in the current healthcare system. It has been recognized as an agent of pneumonia, septicemia, meningitis, urinary tract and wound infections, and is associated with high mortality. Pathogenesis in A. baumannii infections is an outcome of multiple virulence factors, including porins, capsules, and cell wall lipopolysaccharide, enzymes, biofilm production, motility, and iron-acquisition systems, among others. Such virulence factors help the organism to resist stressful environmental conditions and enable development of severe infections. Parallel to increased prevalence of infections caused by A. baumannii, challenging and diverse resistance mechanisms in this pathogen are well recognized, with major classes of antibiotics becoming minimally effective. Through a wide array of antibiotic-hydrolyzing enzymes, efflux pump changes, impermeability, and antibiotic target mutations, A. baumannii models a unique ability to maintain a multidrug-resistant phenotype, further complicating treatment. Understanding mechanisms behind diseases, virulence, and resistance acquisition are central to infectious disease knowledge about A. baumannii. The aims of this review are to highlight infections and disease-producing factors in A. baumannii and to touch base on mechanisms of resistance to various antibiotic classes.

15.
Int J Infect Dis ; 84: 143-150, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31204002

ABSTRACT

OBJECTIVES: Carbapenem resistance in Pseudomonas aeruginosa is growing and results from variable mechanisms. The objectives of the current study were to investigate mechanisms of carbapenem resistance and genetic relatedness of P. aeruginosa isolates recovered in Dubai hospitals. METHODS: From June 2015 through June 2016, carbapenem-nonsusceptible P. aeruginosa were collected from 4 hospitals in Dubai, and subjected to antimicrobial susceptibility testing, molecular investigation of carbapenemases by PCR-sequencing, analysis of outer membrane porin OprD2 and multidrug efflux channel MexAB-OprM levels by qPCR, and fingerprinting by ERIC-PCR. RESULTS: Out of 1969 P. aeruginosa isolated during the study period, 471 (23.9%) showed reduced carbapenem susceptibility. Of these, 37 were analyzed and 32% of them produced VIM-type metallo-ß-lactamases, including VIM-2, VIM-30, VIM-31, and VIM-42, while GES-5 and GES-9 co-existed with VIM in 5.4% of isolates. Outer membrane impermeability was observed in 73% of isolates and 75.6% displayed overproduced MexAB-OprM. ERIC-PCR revealed one large clone including most carbapenemase-producing isolates indicating clonal dissemination. CONCLUSION: This is the first study on carbapenem-nonsusceptible P. aeruginosa from Dubai, incriminating VIM production as well as outer membrane permeability and efflux systems as resistance mechanisms. Further studies on carbapenem-nonsusceptible P. aeruginosa in Dubai are warranted for containment of such health hazard.


Subject(s)
Bacterial Proteins/physiology , Carbapenems/pharmacology , Porins/physiology , Pseudomonas aeruginosa/drug effects , beta-Lactamases/physiology , Cell Membrane Permeability , Cross-Sectional Studies , Drug Resistance, Bacterial , Humans , Pseudomonas aeruginosa/enzymology
16.
BMC Microbiol ; 19(1): 54, 2019 03 08.
Article in English | MEDLINE | ID: mdl-30849936

ABSTRACT

BACKGROUND: Methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosa are becoming difficult to treat with antibiotics whereas Cationic Antimicrobial Peptides (CAMPs) represent promising alternatives. The effects of four CAMPs (LL-37: human cathelicidin, CAMA: cecropin(1-7)-melittin A(2-9) amide, magainin-II and nisin) were investigated against clinical and laboratory S. aureus (n = 10) and P. aeruginosa (n = 11) isolates either susceptible or resistant to antibiotics. Minimal Inhibitory Concentrations (MICs), Minimal Bactericidal Concentrations (MBCs), and bacterial survival rates (2 h post-treatment) were determined by microbroth dilution. The antipseudomonal effects of the antibiotics colistin or imipenem combined to LL-37 or CAMA were also studied. The toxicity of CAMPs used alone and in combination with antibiotics was evaluated on two human lung epithelial cell lines by determining the quantity of released cytoplasmic lactate dehydrogenase (LDH). Attempts to induce bacterial resistance to gentamicin, LL-37 or CAMA were also performed. RESULTS: The results revealed the rapid antibacterial effect of LL-37 and CAMA against both antibiotic susceptible and resistant strains with almost a total reduction in bacterial count 2 h post-treatment. Magainin-II and nisin were less active against tested strains. When antibiotics were combined with LL-37 or CAMA, MICs of colistin decreased up to eight-fold and MICs of imipenem decreased up to four-fold. Cytotoxicity assays revealed non-significant LDH-release suggesting no cell damage in all experiments. Induction of bacterial resistance to LL-37 was transient, tardive and much lower than that to gentamicin and induction of resistance to CAMA was not observed. CONCLUSION: This study showed the potent and rapid antibacterial activity of CAMPs on both laboratory and clinical isolates of S. aureus and P. aeruginosa either susceptible or resistant to antibiotics. Most importantly, CAMPs synergized the efficacy of antibiotics, had non toxic effects on human cells and were associated with transient and low levels of induced resistance.


Subject(s)
Antimicrobial Cationic Peptides/pharmacology , Drug Resistance, Multiple, Bacterial , Methicillin-Resistant Staphylococcus aureus/drug effects , Pseudomonas aeruginosa/drug effects , Anti-Bacterial Agents/pharmacology , Cell Line , Epithelial Cells/drug effects , Humans , L-Lactate Dehydrogenase/analysis , Lung/cytology , Methicillin/pharmacology , Microbial Sensitivity Tests , Nisin/pharmacology , Stem Cells , Cathelicidins
17.
Acta Paediatr ; 107(1): 40-47, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28921627

ABSTRACT

AIM: This Lebanese study tested the hypothesis that differences would exist in the gut microbiota of preterm infants with and without necrotising enterocolitis (NEC), as reported in Western countries. METHODS: This study compared 11 infants with NEC and 11 controls, all born at 27-35 weeks, in three neonatal intensive care units between January 2013 and March 2015. Faecal samples were collected at key time points, and microbiota was analysed by culture, quantitative PCR (qPCR) and temperature temporal gel electrophoresis (TTGE). RESULTS: The cultures revealed that all preterm infants were poorly colonised and harboured no more than seven species. Prior to NEC diagnosis, significant differences were observed by qPCR with a higher colonisation by staphylococci (p = 0.034) and lower colonisations by enterococci (p = 0.039) and lactobacilli (p = 0.048) in the NEC group compared to the healthy controls. Throughout the study, virtually all of the infants were colonised by Enterobacteriaceae at high levels. TTGE analysis revealed no particular clusterisation, showing high interindividual variability. CONCLUSION: The NEC infants were poorly colonised with no more than seven species, and the controls had a more diversified and balanced gut microbiota. Understanding NEC aetiology better could lead to more effective prophylactic interventions and a reduced incidence.


Subject(s)
Enterocolitis, Necrotizing/microbiology , Gastrointestinal Microbiome , Case-Control Studies , Feces/microbiology , Female , Humans , Infant, Newborn , Infant, Premature , Male
18.
Anaerobe ; 43: 4-14, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27833033

ABSTRACT

The establishment and development of the intestinal microbiota is known to be associated with profound short- and long-term effects on the health of full-term infants (FTI), but studies are just starting for preterm infants (PTI). The data also mostly come from western countries and little information is available for the Middle East. Here, we determined the composition and dynamics of the intestinal microbiota during the first month of life for PTI (n = 66) and FTI (n = 17) in Lebanon. Fecal samples were collected weekly and analyzed by quantitative PCR (q-PCR) and temporal temperature gradient gel electrophoresis (TTGE). We observed differences in the establishment and composition of the intestinal microbiota between the two groups. q-PCR showed that PTI were more highly colonized by Staphylococcus than FTI in the first three weeks of life; whereas FTI were more highly colonized by Clostridium clusters I and XI. At one month of life, PTI were mainly colonized by facultative anaerobes and a few strict anaerobes, such as Clostridium cluster I and Bifidobacterium. The type of feeding and antibiotic treatments significantly affected intestinal colonization. TTGE revealed low species diversity in both groups and high inter-individual variability in PTI. Our findings show that PTI had altered intestinal colonization with a higher occurrence of potential pathogens (Enterobacter, Clostridium sp) than FTI. This suggests the need for intervention strategies for PTI to modulate their intestinal microbiota and promote their health.


Subject(s)
Gastrointestinal Microbiome/physiology , Bifidobacterium/genetics , Bifidobacterium/growth & development , Bifidobacterium/isolation & purification , Clostridium/genetics , Clostridium/growth & development , Clostridium/isolation & purification , Denaturing Gradient Gel Electrophoresis , Feces/microbiology , Female , Humans , Infant , Infant, Newborn , Infant, Premature , Intestines/microbiology , Lebanon , Male , Polymerase Chain Reaction , Staphylococcus/genetics , Staphylococcus/growth & development , Staphylococcus/isolation & purification , Tertiary Care Centers
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