Publications by authors named "Hosam M Zowawi"

25 Publications

  • Page 1 of 1

Clinical characteristics and outcomes of patients with heart failure admitted to the intensive care unit with coronavirus disease 2019 (COVID-19): A multicenter cohort study.

Am Heart J Plus 2021 Jul 19;7:100033. Epub 2021 Jul 19.

Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Department of Pharmaceutical Care Services, King Abdulaziz Medical City, Riyadh, Saudi Arabia.

Background: Patients with underlying heart failure (HF) in the setting of COVID-19 who require admission to the intensive care unit (ICU) might present with a unique set of challenges. This study aims to extensively describe the characteristics and outcomes of patients with HF who were admitted to ICU with COVID-19.

Methods: We conducted a multicenter retrospective analysis for all adult patients with HF and an objectively confirmed diagnosis of COVID-19 who were admitted to ICUs between March 1 and August 31, 2020, in Saudi Arabia.

Results: A total of 723 critically ill patients with COVID-19 were admitted into ICUs during the study period: 59 patients with HF and 664 patients with no HF before admission to ICU. Patients with HF had statistically significant more comorbidities, including diabetes mellitus, hypertension, dyslipidemia, atrial fibrillation, and acute coronary syndrome. Moreover, higher baseline severity scores (APACHE II & SOFA score) and nutritional risk (NUTRIC score) were observed in HF patients. Overall, patients with HF had more in-hospital and ICU deaths in comparison to patients without HF: (64.3% vs. 44.6%, -value <0.01) and (54.5% vs. 39%, P-value = 0.02), respectively. Patients with HF had a similar incidence of thrombosis, ICU length of stay, duration of mechanical ventilation, and hospital length of stay compared to patients with no HF.

Conclusion: In this study, patients with HF had more in-hospital and ICU deaths than patients with no HF. Thus, history of HF could be used to help direct case management during hospitalization and possibly dictate proactive COVID-19 care.
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http://dx.doi.org/10.1016/j.ahjo.2021.100033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288252PMC
July 2021

Nationwide Seroprevalence of SARS-CoV-2 in Saudi Arabia.

J Infect Public Health 2021 Jul 24;14(7):832-838. Epub 2021 Apr 24.

King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.

Background: Estimated seroprevalence of Coronavirus Infectious Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is a critical evidence for a better evaluation of the virus spread and monitoring the progress of COVID-19 pandemic in a population. In the Kingdom of Saudi Arabia (KSA), SARS-CoV-2 seroprevalence has been reported in specific regions, but an extensive nationwide study has not been reported. Here, we report a nationwide study to determine the prevalence of SARS-CoV-2 in the population of KSA during the pandemic, using serum samples from healthy blood donors, non-COVID patients and healthcare workers (HCWs) in six different regions of the kingdom, with addition samples from COVID-19 patients.

Methods: A total of 11,703 serum samples were collected from different regions of the KSA including; 5395 samples from residual healthy blood donors (D); 5877 samples from non-COVID patients collected through residual sera at clinical biochemistry labs from non-COVID patients (P); and 400 samples from consented HCWs. To determine the seroprevalence of SARS-CoV-2, all serum samples, in addition to positive control sera from RT-PCR confirmed COVID-19 patients, were subjected to in-house ELISA with a sample pooling strategy, which was further validated by testing individual samples that make up some of the pools, with a statistical estimation method to report seroprevalence estimates.

Results: Overall (combining D and P groups) seroprevalence estimate was around 11% in Saudi Arabia; and was 5.1% (Riyadh), 1.5% (Jazan), 18.4% (Qassim), 20.8% (Hail), 14.7% (ER; Alahsa), and 18.8% in Makkah. Makkah samples were only D group and had a rate of 24.4% and 12.8% in the cities of Makkah and Jeddah, respectively. The seroprevalence in Saudi Arabia across the sampled areas would be 12 times the reported COVID-19 infection rate. Among HCWs, 7.5% (4.95-10.16 CI 95%) had reactive antibodies to SARS-CoV-2 without reporting any previously confirmed infection. This was higher in HCWs with hypertension. The study also presents the demographics and prevalence of co-morbidities in HCWs and subset of non-COVID-19 population.

Interpretation: Our study estimates the overall national serological prevalence of COVID-19 in Saudi Arabia to be 11%, with an apparent disparity between regions. This indicates the prevalence of asymptomatic or mild unreported COVID-19 cases.
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http://dx.doi.org/10.1016/j.jiph.2021.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188888PMC
July 2021

Rapid detection of NDM and VIM carbapenemase encoding genes by recombinase polymerase amplification and lateral flow-based detection.

Eur J Clin Microbiol Infect Dis 2021 May 11. Epub 2021 May 11.

UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Royal Brisbane and Women's Hospital Campus, Brisbane, Australia.

Carbapenemase-producing organisms (CPOs) pose a serious clinical threat and rapid detection tools are essential to aid in patient management. We developed rapid and simple molecular tests to detect bla and bla carbapenemase genes using recombinase polymerase amplification (RPA) combined with a lateral flow detection. The tests could provide results in approximately 15 min when using DNA extracts, with limits of detection of 9.2 copies/μl for the bla assay and 7.5 copies/μl for bla assay, and successfully detected all isolates harbouring the carbapenemase encoding genes in a panel of 57 isolates. These RPA tests may be suitable for use in low-resource settings to tailor rapid implementation of infection control precautions and antibiotic stewardship.
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http://dx.doi.org/10.1007/s10096-021-04267-6DOI Listing
May 2021

Semi-mechanistic PK/PD modelling of meropenem and sulbactam combination against carbapenem-resistant strains of Acinetobacter baumannii.

Eur J Clin Microbiol Infect Dis 2021 Sep 22;40(9):1943-1952. Epub 2021 Apr 22.

Centre for Translational Anti-infective Pharmacodynamics, School of Pharmacy, Pharmacy Australia Centre of Excellence, University of Queensland, Level 4, 20 Cornwall Street, Woolloongabba, QLD, 4102, Australia.

Due to limited treatment options for carbapenem-resistant Acinetobacter baumannii (CR-AB) infections, antibiotic combinations are commonly used. In this study, we explored the potential efficacy of meropenem-sulbactam combination (MEM/SUL) against CR-AB. The checkerboard method was used to screen for synergistic activity of MEM/SUL against 50 clinical CR-AB isolates. Subsequently, time-kill studies against two CR-AB isolates were performed. Time-kill data were described using a semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model. Subsequently, Monte Carlo simulations were performed to estimate the probability of 2-log kill, 1-log kill or stasis at 24-h following combination therapy. The MEM/SUL demonstrated synergy against 28/50 isolates. No antagonism was observed. The MIC50 and MIC of MEM/SUL were decreased fourfold, compared to the monotherapy MIC. In the time-kill studies, the combination displayed synergistic killing against both isolates at the highest clinically achievable concentrations. At concentrations equal to the fractional inhibitory concentration, synergism was observed against one isolate. The PK/PD model adequately delineated the data and the interaction between meropenem and sulbactam. The effect of the combination was driven by sulbactam, with meropenem acting as a potentiator. The simulations of various dosing regimens revealed no activity for the monotherapies. At best, the MEM/SUL regimen of 2 g/4 g every 8 h demonstrated a probability of target attainment of 2-log kill at 24 h of 34%. The reduction in the MIC values and the achievement of a moderate PTA of a 2-log reduction in bacterial burden demonstrated that MEM/SUL may potentially be effective against some CR-AB infections.
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http://dx.doi.org/10.1007/s10096-021-04252-zDOI Listing
September 2021

Portable RT-PCR System: a Rapid and Scalable Diagnostic Tool for COVID-19 Testing.

J Clin Microbiol 2021 04 20;59(5). Epub 2021 Apr 20.

Liver Transplantation Unit, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

Combating the ongoing coronavirus disease 2019 (COVID-19) pandemic demands accurate, rapid, and point-of-care testing with fast results to triage cases for isolation and treatment. The current testing relies on reverse transcriptase PCR (RT-PCR), which is routinely performed in well-equipped laboratories by trained professionals at specific locations. However, during busy periods, high numbers of samples queued for testing can delay the test results, impacting efforts to reduce the infection risk. Besides, the absence of well-established laboratories at remote sites and low-resourced environments can contribute to a silent spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These reasons compel the need to accommodate point-of-care testing for COVID-19 that meets the ASSURED criteria (ffordable, ensitive, pecific, ser-friendly, apid and robust, quipment-free, and eliverable). This study assessed the agreement and accuracy of the portable Biomeme SARS-CoV-2 system against the gold standard tests. Nasopharyngeal and nasal swabs were used. Of the 192 samples tested using the Biomeme SARS-CoV-2 system, the results from 189 samples (98.4%) were in agreement with the reference standard-of-care RT-PCR testing for SARS-CoV-2. The portable system generated simultaneous results for nine samples in 80 min with high positive and negative percent agreements of 99.0% and 97.8%, respectively. We performed separate testing in a sealed glove box, offering complete biosafety containment. Thus, the Biomeme SARS-CoV-2 system can help decentralize COVID-19 testing and offer rapid test results for patients in remote and low-resourced settings.
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http://dx.doi.org/10.1128/JCM.03004-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091859PMC
April 2021

Near-Infrared Spectroscopy Evaluations for the Differentiation of Carbapenem-Resistant from Susceptible Enterobacteriaceae Strains.

Diagnostics (Basel) 2020 Sep 23;10(10). Epub 2020 Sep 23.

The University of Queensland Centre for Clinical Research, Faculty of Medicine, Brisbane 4029, Queensland, Australia.

Antimicrobial Resistance (AMR) caused by Carbapenem-Resistant Enterobacteriaceae (CRE) is a global threat. Accurate identification of these bacterial species with associated AMR is critical for their management. While highly accurate methods to detect CRE are available, they are costly, timely and require expert skills, making their application infeasible in low-resource settings. Here, we investigated the potential of Near-Infrared Spectroscopy (NIRS) for a range of applications: (i) the detection and differentiation of isolates of two pathogenic Enterobacteriaceae species, and , and (ii) the differentiation of carbapenem resistant and susceptible . NIRS has successfully differentiated between and isolates with a predictive accuracy of 89.04% (95% CI; 88.7-89.4%). isolates harbouring carbapenem-resistance determinants were differentiated from susceptible strains with an accuracy of 85% (95% CI; 84.2-86.1%). To our knowledge, this is the largest proof of concept demonstration for the utility and feasibility of NIRS to rapidly differentiate between and as well as carbapenem-resistant from susceptible strains.
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http://dx.doi.org/10.3390/diagnostics10100736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598181PMC
September 2020

First report of harboring in Saudi Arabia.

Antimicrob Resist Infect Control 2019 19;8:203. Epub 2019 Dec 19.

1Pathogen Genomics Laboratory, Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia.

Background: Nosocomial infections caused by multi-drug resistant are a global public health threat that ought to be promptly identified, reported, and addressed accurately. Many carbapenem-resistant -associated genes have been identified in Saudi Arabia but not the endemic carbapenemases (KPCs), which are encoded by genes. KPCs are known for their exceptional spreading potential.

Methods: We collected  = 286 multi-drug resistant (MDR) isolates as part of screening for resistant patterns from a tertiary hospital in Saudi Arabia between 2014 and 2018. Antimicrobial susceptibility testing was carried out using both VITEK II and the broth microdilution of all collected isolates. Detection of resistance-conferring genes was carried out using Illumina whole-genome shotgun sequencing and PacBio SMRT sequencing protocols.

Results: A Carbapenem-resistant (CRE) subsp. strain was identified as a novel ST-3510 carrying a carbapenemase encoding gene. The isolate, designated as NGKPC-421, was obtained from shotgun Whole Genome Sequencing (WGS) surveillance of 286 MDR . clinical isolates. The NGKPC-421 isolate was collected from a septic patient in late 2017 and was initially misidentified as . The sequencing and assembly of the NGKPC-421 genome resulted in the identification of a putative ~ 39.4 kb IncX6 plasmid harboring a gene, flanked by transposable elements (IS -IS).

Conclusion: This is the first identification of a KPC-2-producing CRE in the Gulf region. The impact on this finding is of major concern to the public health in Saudi Arabia, considering that it is the religious epicenter with a continuous mass influx of pilgrims from across the world. Our study strongly highlights the importance of implementing rapid sequencing-based technologies in clinical microbiology for precise taxonomic classification and monitoring of antimicrobial resistance patterns.
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http://dx.doi.org/10.1186/s13756-019-0653-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923860PMC
July 2020

Bacterial identification using a SCIEX 5800 TOF/TOF MALDI research instrument and an external database.

J Microbiol Methods 2019 09 7;164:105685. Epub 2019 Aug 7.

The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia.

In our current study we were identifying 26 bacterial isolates using a SCIEX 5800 TOF/TOF MALDI instrument and an external database. The results were compared with the results of a Vitek® MS system and in case of discrepancies at the species level 16s rRNA sequencing was performed for further verification.
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http://dx.doi.org/10.1016/j.mimet.2019.105685DOI Listing
September 2019

Skin colonization at peripheral intravenous catheter insertion sites increases the risk of catheter colonization and infection.

Am J Infect Control 2019 12 19;47(12):1484-1488. Epub 2019 Jul 19.

Alliance for Vascular Access Teaching and Research (AVATAR) Group, Griffith University, Brisbane, Australia; Menzies Health Institute Queensland, and School of Nursing and Midwifery, Griffith University, Brisbane, Australia; Royal Brisbane and Women's Hospital, Brisbane, Australia.

Background: Peripheral intravenous catheters (PIVCs) break the skin barrier, and preinsertion antiseptic disinfection and sterile dressings are used to reduce risk of catheter-related bloodstream infection (CRBSI). In this study, the impact of PIVC skin site colonization on tip colonization and the development of CRBSI was investigated.

Methods: A total of 137 patients' PIVC skin site swabs and paired PIVC tips were collected at catheter removal, cultured, and bacterial species and clonality were identified.

Results: Of 137 patients, 45 (33%) had colonized skin sites and/or PIVC tips. Of 16 patients with paired colonization of both the skin site and PIVC tips, 11 (69%) were colonized with the same bacterial species. Of these, 77% were clonally related, including 1 identical clone of Pseudomonas aeruginosa in a patient with systemic infection and the same organism identified in blood culture.

Conclusions: The results demonstrate that opportunistic pathogen colonization at the skin site poses a significant risk for PIVC colonization and CRBSI. Further research is needed to improve current preinsertion antiseptic disinfection of PIVC skin site and the sterile insertion procedure to potentially reduce PIVC colonization and infection risk.
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http://dx.doi.org/10.1016/j.ajic.2019.06.002DOI Listing
December 2019

Evaluation of the SpeeDx Carba (beta) multiplex real-time PCR assay for detection of NDM, KPC, OXA-48-like, IMP-4-like and VIM carbapenemase genes.

BMC Infect Dis 2019 Jul 2;19(1):571. Epub 2019 Jul 2.

The University of Queensland, UQ Centre for Clinical Research, Brisbane, Queensland, Australia.

Background: Carbapenemase-producing organisms (CPOs) have emerged as antibiotic-resistant bacteria of global concern. Here we assessed the performance of the Carba (beta) assay, a multiplex real-time PCR assay developed by SpeeDx for the detection of key carbapenemase-encoding genes: KPC, NDM, OXA-48-like, IMP-4-like, and VIM.

Methods: DNA extracts of 180 isolates were tested with the Carba (beta) assay, using previously validated in-house TaqMan probe assays for the relevant carbapenemase genes as the reference standard. The Carba (beta) assay was then directly used to screen 460 DNA extracts of faecal specimens, with positive results subjected to the aforementioned in-house assays plus Sanger sequencing.

Results: The Carba (beta) assay correctly identified the presence of the respective carbapenemase genes in 154 of 156 isolates and provided negative results for all 24 non-CPO isolates. Two isolates provided positive results for OXA-48-like carbapenemase by the Carba (beta) assay only. The Carba (beta) assay had sensitivities of 100% for all targets, and specificities of 100% for KPC, NDM, IMP-4-like, and VIM targets, and 98.5% for OXA-48-like targets. When applied directly to faecal specimens, eight samples were positive by the Carba (beta) assay, two of which were confirmed by in-house TaqMan probe PCR or DNA sequencing.

Conclusions: The Carba (beta) assay is highly sensitive and specific for detecting key carbapenemase genes in isolates. Further testing is required to assess this assay's suitability for direct screening of clinical specimens.
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http://dx.doi.org/10.1186/s12879-019-4176-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604329PMC
July 2019

Antimicrobial resistance: A round table discussion on the "One Health" concept from the Gulf Cooperation Council Countries. Part Two: A focus on Human Health.

J Infect Public Health 2018 Nov - Dec;11(6):778-783. Epub 2018 Oct 29.

Saudi Food and Drug Administration, Riyadh, Saudi Arabia.

The Gulf Cooperation Council Center for Infection Control (GCC-IC) has moved forward over the past several years on the antimicrobial resistance (AMR) agenda. Many of the GCC countries have now developed a national plan to combat AMR and have engaged the leadership of the involved sectors in the discussion on how to mitigate this threat. During the first meeting for the GCC-IC center on AMR, which took place early 2015, the roadmap for combating AMR was developed [1] and since then much more has been done. We present here the discussion that took place during the second GCC-IC center meeting on AMR where not only have the countries presented their progress, but we conducted 2 round table discussions inviting international and regional experts in the field to share their thoughts, progress and knowledge on this topic [2]. Within is the 2nd round table discussion at the 2017 GCC AMR meeting which took place in Riyadh, Saudi Arabia, April 2017. Where the 1st round table discussion during this meeting addressed the role of leadership in managing AMR [2].
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http://dx.doi.org/10.1016/j.jiph.2018.05.008DOI Listing
December 2018

Discovery of -Mediated Colistin Resistance in a Highly Virulent Escherichia coli Lineage.

mSphere 2018 10 10;3(5). Epub 2018 Oct 10.

School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia

Resistance to last-line polymyxins mediated by the plasmid-borne mobile colistin resistance gene () represents a new threat to global human health. Here we present the complete genome sequence of an -positive multidrug-resistant strain (MS8345). We show that MS8345 belongs to serotype O2:K1:H4, has a large 241,164-bp IncHI2 plasmid that carries 15 other antibiotic resistance genes (including the extended-spectrum β-lactamase ) and 3 putative multidrug efflux systems, and contains 14 chromosomally encoded antibiotic resistance genes. MS8345 also carries a large ColV-like virulence plasmid that has been associated with bacteremia. Whole-genome phylogeny revealed that MS8345 clusters within a discrete clade in the sequence type 95 (ST95) lineage, and MS8345 is very closely related to the highly virulent O45:K1:H4 clone associated with neonatal meningitis. Overall, the acquisition of a plasmid carrying resistance to colistin and multiple other antibiotics in this virulent lineage is concerning and might herald an era where the empirical treatment of ST95 infections becomes increasingly more difficult. ST95 is a globally disseminated clone frequently associated with bloodstream infections and neonatal meningitis. However, the ST95 lineage is defined by low levels of drug resistance amongst clinical isolates, which normally provides for uncomplicated treatment options. Here, we provide the first detailed genomic analysis of an ST95 isolate that has both high virulence potential and resistance to multiple antibiotics. Using the genome, we predicted its virulence and antibiotic resistance mechanisms, which include resistance to last-line antibiotics mediated by the plasmid-borne gene. Finding an ST95 isolate resistant to nearly all antibiotics that also has a high virulence potential is of major clinical importance and underscores the need to monitor new and emerging trends in antibiotic resistance development in this important global lineage.
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http://dx.doi.org/10.1128/mSphere.00486-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180223PMC
October 2018

Identification of carbapenem-resistant Pseudomonas aeruginosa in selected hospitals of the Gulf Cooperation Council States: dominance of high-risk clones in the region.

J Med Microbiol 2018 Jun 17;67(6):846-853. Epub 2018 Apr 17.

The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia.

Purpose: The molecular epidemiology and resistance mechanisms of carbapenem-resistant Pseudomonas aeruginosa (CRPA) were determined in hospitals in the countries of the Gulf Cooperation Council (GCC), namely, Saudi Arabia, the United Arab Emirates, Oman, Qatar, Bahrain and Kuwait.

Methodology: Isolates were screened for common carbapenem-resistance genes by PCR. Relatedness between isolates was assessed using previously described genotyping methods: an informative-single nucleotide polymorphism MassARRAY iPLEX assay (iPLEX20SNP) and the enterobacterial repetitive intergenic consensus (ERIC)-PCR assay, with selected isolates being subjected to multilocus sequence typing (MLST). Ninety-five non-repetitive isolates that were found to be resistant to carbapenems were subjected to further investigation.Results/Key findings. The most prevalent carbapenemase-encoding gene, blaVIM-type, was found in 37/95 (39 %) isolates, while only 1 isolate (from UAE) was found to have blaIMP-type. None of the CRPA were found to have blaNDM-type or blaKPC-type. We found a total of 14 sequence type (ST) clusters, with 4 of these clusters being observed in more than 1 country. Several clusters belonged to the previously recognized internationally disseminated high-risk clones ST357, ST235, ST111, ST233 and ST654. We also found the less predominant ST316, ST308 and ST823 clones, and novel MLST types (ST2010, ST2011, ST2012 and ST2013), in our collection.

Conclusion: Overall our data show that 'high-risk' CRPA clones are now detected in the region and highlight the need for strategies to limit further spread of such organisms, including enhanced surveillance, infection control precautions and further promotion of antibiotic stewardship programmes.
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http://dx.doi.org/10.1099/jmm.0.000730DOI Listing
June 2018

Whole genome analysis of cephalosporin-resistant Escherichia coli from bloodstream infections in Australia, New Zealand and Singapore: high prevalence of CMY-2 producers and ST131 carrying blaCTX-M-15 and blaCTX-M-27.

J Antimicrob Chemother 2018 03;73(3):634-642

University of Queensland, UQ Centre for Clinical Research, Royal Brisbane & Women's Hospital, Queensland, Australia.

Objectives: To characterize MDR Escherichia coli from bloodstream infections (BSIs) in Australia, New Zealand and Singapore.

Methods: We collected third-generation cephalosporin-resistant (3GC-R) E. coli from blood cultures in patients enrolled in a randomized controlled trial from February 2014 to August 2015. WGS was used to characterize antibiotic resistance genes, MLST, plasmids and phylogenetic relationships. Antibiotic susceptibility was determined using disc diffusion and Etest.

Results: A total of 70 3GC-R E. coli were included, of which the majority were ST131 (61.4%). BSI was most frequently from a urinary source (69.6%), community associated (62.9%) and in older patients (median age 71 years). The median Pitt score was 1 and ICU admission was infrequent (3.1%). ST131 possessed more acquired resistance genes than non-ST131 (P = 0.003). Clade C1/C2 ST131 predominated (30.2% and 53.5% of ST131, respectively) and these were all ciprofloxacin resistant. All clade A ST131 (n = 6) were community associated. The predominant ESBL types were blaCTX-M (80.0%) and were strongly associated with ST131 (95% carried blaCTX-M), with the majority blaCTX-M-15. Clade C1 was associated with blaCTX-M-14 and blaCTX-M-27, whereas blaCTX-M-15 predominated in clade C2. Plasmid-mediated AmpC genes (mainly blaCMY-2) were frequent (17.1%) but were more common in non-ST131 (P < 0.001) isolates from Singapore and Brisbane. Two strains carried both blaCMY-2 and blaCTX-M. The majority of plasmid replicon types were IncF.

Conclusions: In a prospective collection of 3GC-R E. coli causing BSI, community-associated Clade C1/C2 ST131 predominate in association with blaCTX-M ESBLs, although a significant proportion of non-ST131 strains carried blaCMY-2.
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http://dx.doi.org/10.1093/jac/dkx466DOI Listing
March 2018

Multihospital Occurrence of Pan-Resistant Klebsiella pneumoniae Sequence Type 147 with an IS-Directed Insertion in the Gene in the United Arab Emirates.

Antimicrob Agents Chemother 2017 07 27;61(7). Epub 2017 Jun 27.

Department of Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates

The emergence of pan-resistant strains is an increasing concern. In the present study, we describe a cluster of 9 pan-resistant sequence type 147 (ST147) isolates encountered in 4 patients over nearly 1 year in 3 hospitals of the United Arab Emirates (UAE). The isolates exhibited highly similar genotypes. All produced chromosomally encoded OXA-181, and the majority also produced the NDM-5 carbapenemase. As with the previously described single isolate from the UAE, MS6671, the was disrupted by a functional, IS-driven insertion causing resistance to carbapenems. The mutation was successfully complemented with an intact gene, indicating that it was responsible for colistin resistance. was located within a resistance island of an approximately 100-kb IncFII plasmid carrying , (A), , , , , , and resistance genes. Sequencing this plasmid (pABC143-NDM) revealed that its backbone was nearly identical to that of plasmid pMS6671E from which several resistance genes, including , had been deleted. More extensive similarities of the backbone and the resistance island were found between pABC143C-NDM and the -carrying IncFII plasmids of two ST147 isolates from South Korea, one of which was colistin resistant, and both also produced OXA-181. Notably, one of these strains was isolated from a patient transferred from the UAE. Our data show that this pan-resistant clone has an alarming capacity to maintain itself over an extended period of time and is even likely to be transmitted internationally.
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http://dx.doi.org/10.1128/AAC.00418-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487649PMC
July 2017

Detection of carbapenemase activity in Enterobacteriaceae using LC-MS/MS in comparison with the neo-rapid CARB kit using direct visual assessment and colorimetry.

J Microbiol Methods 2016 12 11;131:68-72. Epub 2016 Oct 11.

University of Queensland, UQ Centre for Clinical Research, Herston, QLD, Australia.

It has been described that the sensitivity of the Carba NP test may be low in the case of OXA-48-like carbapenamases and mass spectrometry based methods as well as a colorimetry based method have been described as alternatives. We evaluated 84 Enterobacteriaceae isolates including 31 OXA-48-like producing isolates and 13 isolates that produced either an imipenemase (IMP; n=8), New Delhi metallo-β-lactamase (NDM; n=3), or Klebsiella pneumoniae carbapenemase (KPC; n=2), as well as 40 carbapenemase negative Enterobacteriaceae isolates. We used the Neo-Rapid CARB kit, assessing the results with the unaided eye and compared it with a colorimetric approach. Furthermore, we incubated the isolates in growth media with meropenem and measured the remaining meropenem after one and 2h of incubation, respectively, using liquid chromatography tandem mass spectrometry (LC-MS/MS). Whilst all carbapenemase producing isolates with the exception of the OXA-244 producer tested positive for both the Neo-rapid CARB test using the unaided eye or colorimetry, and the 13 isolates producing either IMP, NDM or KPC hydrolysed the meropenem in the media almost completely after 2h of incubation, the 31 OXA-48-like producing isolates exhibited very variable hydrolytic activity when incubated in growth media with meropenem. In our study, the Neo-Rapid CARB test yielded a sensitivity of 98% for both the traditional and the colorimetric approach with a specificity of 95% and 100% respectively. Our results indicate that the Neo-Rapid CARB test may have use for the detection of OXA-48 type carbapenemases and that it may be particularly important to ensure bacterial lysis for the detection of these weaker hydrolysers.
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http://dx.doi.org/10.1016/j.mimet.2016.10.005DOI Listing
December 2016

Antimicrobial resistance in Saudi Arabia. An urgent call for an immediate action.

Authors:
Hosam M Zowawi

Saudi Med J 2016 Sep;37(9):935-40

From the College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia. E-mail.

Antimicrobial resistance (AMR) is increasingly being highlighted as an urgent public and animal health issue worldwide. This issue is well demonstrated in bacteria that are resistant to last-line antibiotics, suggesting a future with untreatable infections. International agencies have suggested combating strategies against AMR. Saudi Arabia has several challenges that can stimulate the emergence and spread of multidrug-resistant bacteria. Tackling these challenges need efforts from multiple sectors to successfully control the spread and emergence of AMR in the country. Actions should include active surveillance to monitor the emergence and spread of AMR. Infection prevention and control precautions should also be optimized to limit further spread. Raising awareness is essential to limit inappropriate antibiotics use, and the antibiotic stewardship programs in hospital settings, outpatients, and community pharmacies, should regulate the ongoing use of antimicrobials.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039611PMC
http://dx.doi.org/10.15537/smj.2016.9.16139DOI Listing
September 2016

Stepwise evolution of pandrug-resistance in Klebsiella pneumoniae.

Sci Rep 2015 Oct 19;5:15082. Epub 2015 Oct 19.

The University of Queensland, Centre for Clinical Research (UQCCR), Herston QLD 4029, Australia.

Carbapenem resistant Enterobacteriaceae (CRE) pose an urgent risk to global human health. CRE that are non-susceptible to all commercially available antibiotics threaten to return us to the pre-antibiotic era. Using Single Molecule Real Time (SMRT) sequencing we determined the complete genome of a pandrug-resistant Klebsiella pneumoniae isolate, representing the first complete genome sequence of CRE resistant to all commercially available antibiotics. The precise location of acquired antibiotic resistance elements, including mobile elements carrying genes for the OXA-181 carbapenemase, were defined. Intriguingly, we identified three chromosomal copies of an ISEcp1-bla(OXA-181) mobile element, one of which has disrupted the mgrB regulatory gene, accounting for resistance to colistin. Our findings provide the first description of pandrug-resistant CRE at the genomic level, and reveal the critical role of mobile resistance elements in accelerating the emergence of resistance to other last resort antibiotics.
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http://dx.doi.org/10.1038/srep15082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4609946PMC
October 2015

Genetic Contexts of blaNDM-1 in Patients Carrying Multiple NDM-Producing Strains.

Antimicrob Agents Chemother 2015 Dec 21;59(12):7405-10. Epub 2015 Sep 21.

The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia.

The carbapenem resistance determinant blaNDM-1 has been found in various Gram-negative bacteria and upon different plasmid replicon types (Inc). Here, we present four patients within two hospitals in Pakistan harboring between two and four NDM-1-producing Gram-negative bacilli of different species coresident in their stool samples. We characterize the blaNDM-1 genetic contexts of these 11 NDM-1-producing Gram-negative bacilli in addition to other antimicrobial resistance mechanisms, plasmid replicon profiles, and sequence types (STs) in order to understand the underlying acquisition mechanisms of carbapenem resistance within these bacteria. Two common plasmid types (IncN2 and IncA/C) were identified to carry blaNDM-1 among the six different bacterial species isolated from the four patients. Two of these strains were novel Citrobacter freundii ST 20 and ST 21. The same IncN2-type blaNDM-1 genetic context was found in all four patients and within four different species. The IncA/C-type blaNDM-1 genetic context was found in two different species and in two of the four patients. Combining genetic context characterization with other molecular epidemiology methods, we were able to establish the molecular epidemiological links between genetically unrelated bacterial species by linking their acquisition of an IncN2 or IncA/C plasmid carrying blaNDM-1 for carbapenem resistance. By combining plasmid characterization and in-depth genetic context assessment, this analysis highlights the importance of plasmids in antimicrobial resistance. It also provides a novel approach for investigating the underlying mechanisms of blaNDM-1-related spread between bacterial species and genera via plasmids.
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http://dx.doi.org/10.1128/AAC.01319-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4649221PMC
December 2015

The emerging threat of multidrug-resistant Gram-negative bacteria in urology.

Nat Rev Urol 2015 Oct 1;12(10):570-84. Epub 2015 Sep 1.

The University of Queensland, UQ Centre for Clinical Research, Building 71/918 Royal Brisbane Hospital, Herston, QLD 4006, Australia.

Antibiotic resistance in Gram-negative uropathogens is a major global concern. Worldwide, the prevalence of Enterobacteriaceae that produce extended-spectrum β-lactamase or carbapenemase enzymes continues to increase at alarming rates. Likewise, resistance to other antimicrobial agents including aminoglycosides, sulphonamides and fluoroquinolones is also escalating rapidly. Bacterial resistance has major implications for urological practice, particularly in relation to catheter-associated urinary tract infections (UTIs) and infectious complications following transrectal-ultrasonography-guided biopsy of the prostate or urological surgery. Although some new drugs with activity against Gram-negative bacteria with highly resistant phenotypes will become available in the near future, the existence of a single agent with activity against the great diversity of resistance is unlikely. Responding to the challenges of Gram-negative resistance will require a multifaceted approach including considered use of current antimicrobial agents, improved diagnostics (including the rapid detection of resistance) and surveillance, better adherence to basic measures of infection prevention, development of new antibiotics and research into non-antibiotic treatment and preventive strategies.
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http://dx.doi.org/10.1038/nrurol.2015.199DOI Listing
October 2015

PME-1-producing Pseudomonas aeruginosa in Qatar.

Antimicrob Agents Chemother 2015 13;59(6):3692-3. Epub 2015 Apr 13.

The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia.

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http://dx.doi.org/10.1128/AAC.00424-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4432198PMC
February 2016

Molecular epidemiology of carbapenem-resistant Acinetobacter baumannii isolates in the Gulf Cooperation Council States: dominance of OXA-23-type producers.

J Clin Microbiol 2015 Mar 7;53(3):896-903. Epub 2015 Jan 7.

The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia.

The molecular epidemiology and mechanisms of resistance of carbapenem-resistant Acinetobacter baumannii (CRAB) were determined in hospitals in the states of the Cooperation Council for the Arab States of the Gulf (Gulf Cooperation Council [GCC]), namely, Saudi Arabia, United Arab Emirates, Oman, Qatar, Bahrain, and Kuwait. Isolates were subjected to PCR-based detection of antibiotic resistance genes and repetitive sequence-based PCR (rep-PCR) assessments of clonality. Selected isolates were subjected to multilocus sequence typing (MLST). We investigated 117 isolates resistant to carbapenem antibiotics (either imipenem or meropenem). All isolates were positive for OXA-51. The most common carbapenemases were the OXA-23-type, found in 107 isolates, followed by OXA-40-type (OXA-24-type), found in 5 isolates; 3 isolates carried the ISAba1 element upstream of blaOXA-51-type. No OXA-58-type, NDM-type, VIM-type, or IMP-type producers were detected. Multiple clones were detected with 16 clusters of clonally related CRAB. Some clusters involved hospitals in different states. MLST analysis of 15 representative isolates from different clusters identified seven different sequence types (ST195, ST208, ST229, ST436, ST450, ST452, and ST499), as well as three novel STs. The vast majority (84%) of the isolates in this study were associated with health care exposure. Awareness of multidrug-resistant organisms in GCC states has important implications for optimizing infection control practices; establishing antimicrobial stewardship programs within hospital, community, and agricultural settings; and emphasizing the need for establishing regional active surveillance systems. This will help to control the spread of CRAB in the Middle East and in hospitals accommodating transferred patients from this region.
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http://dx.doi.org/10.1128/JCM.02784-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4390656PMC
March 2015

Molecular characterization of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae in the countries of the Gulf cooperation council: dominance of OXA-48 and NDM producers.

Antimicrob Agents Chemother 2014 Jun 17;58(6):3085-90. Epub 2014 Mar 17.

The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia.

The molecular epidemiology and mechanisms of resistance of carbapenem-resistant Enterobacteriaceae (CRE) were determined in hospitals in the countries of the Gulf Cooperation Council (GCC), namely, Saudi Arabia, United Arab Emirates, Oman, Qatar, Bahrain, and Kuwait. Isolates were subjected to PCR-based detection of antibiotic-resistant genes and repetitive sequence-based PCR (rep-PCR) assessments of clonality. Sixty-two isolates which screened positive for potential carbapenemase production were assessed, and 45 were found to produce carbapenemase. The most common carbapenemases were of the OXA-48 (35 isolates) and NDM (16 isolates) types; 6 isolates were found to coproduce the OXA-48 and NDM types. No KPC-type, VIM-type, or IMP-type producers were detected. Multiple clones were detected with seven clusters of clonally related Klebsiella pneumoniae. Awareness of CRE in GCC countries has important implications for controlling the spread of CRE in the Middle East and in hospitals accommodating patients transferred from the region.
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http://dx.doi.org/10.1128/AAC.02050-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068443PMC
June 2014

β-Lactamase production in key gram-negative pathogen isolates from the Arabian Peninsula.

Clin Microbiol Rev 2013 Jul;26(3):361-80

The University of Queensland, UQ Centre for Clinical Research, Herston, Queensland, Australia.

SUMMARY Infections due to Gram-negative bacilli (GNB) are a leading cause of morbidity and mortality worldwide. The extent of antibiotic resistance in GNB in countries of the Gulf Cooperation Council (GCC), namely, Saudi Arabia, United Arab Emirates, Kuwait, Qatar, Oman, and Bahrain, has not been previously reviewed. These countries share a high prevalence of extended-spectrum-β-lactamase (ESBL)- and carbapenemase-producing GNB, most of which are associated with nosocomial infections. Well-known and widespread β-lactamases genes (such as those for CTX-M-15, OXA-48, and NDM-1) have found their way into isolates from the GCC states. However, less common and unique enzymes have also been identified. These include PER-7, GES-11, and PME-1. Several potential risk factors unique to the GCC states may have contributed to the emergence and spread of β-lactamases, including the unnecessary use of antibiotics and the large population of migrant workers, particularly from the Indian subcontinent. It is clear that active surveillance of antimicrobial resistance in the GCC states is urgently needed to address regional interventions that can contain the antimicrobial resistance issue.
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http://dx.doi.org/10.1128/CMR.00096-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3719487PMC
July 2013
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