AHMED HAMOUDA - Academia.edu (original) (raw)

Papers by AHMED HAMOUDA

Reviews in Medical Microbiology, 2007

ABSTRACT The extended-spectrum β-lactamases have evolved owing to the extensive use of the oxyimi... more ABSTRACT The extended-spectrum β-lactamases have evolved owing to the extensive use of the oxyimino-cephalosporins, and have greatly reduced the treatment options for serious infections. Acinetobacter baumannii is becoming an increasingly important multiresistant nosocomial pathogen due to the carriage of class D OXA-type β-lactamases. The OXA-23-like, OXA-40-like and OXA-58-like β-lactamases confer carbapenem resistance and are increasingly being found in association with a diversity of mobile genetic elements. High prevalence of OXA-40-like enzymes on the Iberian Peninsula, OXA-58-like enzymes across Europe and very high prevalence of OXA-23-like enzymes in South America and Asia are of concern. The intrinsic OXA-51-like enzymes of A. baumannii may confer carbapenem resistance when overexpressed, and form a large enzyme family. Similar patterns are beginning to be seen for the OXA-type β-lactamases, which were previously seen in the emergence of the extended-spectrum β-lactamases, the continuation of which would pose a grave threat to the antibiotic era.

The Journal of antimicrobial chemotherapy, 2010

The detection in Acinetobacter genospecies 3 isolates of OXA-type carbapenemases, resulting in re... more The detection in Acinetobacter genospecies 3 isolates of OXA-type carbapenemases, resulting in reduced susceptibility to carbapenem antibiotics, is increasingly reported. We identified an Acinetobacter genospecies 3 isolate carrying the gene for OXA-58 and aimed to resolve the genetic environment surrounding the bla(OXA-58) gene.

International journal of antimicrobial agents, 2011

High prevalence of unrelated multidrug-resistant Acinetobacter baumannii isolates in Pakistani mi... more High prevalence of unrelated multidrug-resistant Acinetobacter baumannii isolates in Pakistani military hospitals Sir, Nosocomial infections with multidrug-resistant (MDR) Acinetobacter baumannii are an increasing problem worldwide, with the emergence of carbapenem resistance conferred by acquired OXAtype carbapenemases such as the OXA-23 and OXA-58 families of particular concern. Frequently both bla OXA-23 and bla OXA-58 are identified in association with insertion sequences (IS), responsible for the mobilisation and expression of resistance genes. The transposons Tn2006, comprising the bla OXA-23 gene bracketed by two ISAba1 elements, and Tn2008, comprising a single ISAba1 element upstream of the bla OXA-23 gene, have been found in multiple globally distributed locations and are likely partially responsible for the increasing prevalence of the bla OXA-23 gene [1]. Despite high levels of carbapenem resistance in Pakistan [2], molecular surveillance studies are scarce for the region. The aim of this study was to examine the antimicrobial resistance properties of A. baumannii isolates from Pakistan, with a particular focus on carbapenem resistance. Twenty clinical bacterial isolates obtained over 2 months from two military hospitals in Rawalpindi, Pakistan, were biochem

Clinical Microbiology and Infection, 2007

Journal of Antimicrobial Chemotherapy, 2011

To establish the molecular epidemiology and antimicrobial resistance pattern of extendedspectrum ... more To establish the molecular epidemiology and antimicrobial resistance pattern of extendedspectrum b-lactamase (ESBL)-producing Enterobacteriaceae harbouring bla CTX-M in Glasgow, Scotland. Methods: During a 12 week period, Enterobacteriaceae isolates obtained from urine samples were collected and susceptibility testing performed. Isolates were screened for the presence of bla CTX-M by multiplex PCR and selected Escherichia coli genes were subsequently sequenced. PFGE analysis was performed on selected E. coli isolates in order to identify clonal relationships. Results: There were 155 phenotypically confirmed non-duplicate Enterobacteriaceae isolates obtained from urine samples. bla CTX-M was identified in 131/155 (84.5%) of the ESBL-producing isolates, with CTX-M group 1 enzymes accounting for 103/131 (78.6%) of these. The remaining 24 isolates carried other bla CTX-M types, including CTX-M group 2, CTX-M group 9 and an unidentifiable combination designated CTX-M group G2/Gx. A sample of 46/97 (47.4%) CTX-M-positive E. coli isolates was chosen for PFGE and demographic information regarding the source of the isolates was collated. Eight E. coli clusters were identified by PFGE; however, they did not achieve the 85% cutoff to demonstrate clonality. Nitrofurantoin resistance was significantly greater in the E. coli isolates expressing a non-CTX-M group 1 ESBL when compared with the E. coli isolates expressing a CTX-M group 1 ESBL. Conclusions: As seen in other British studies, bla CTX-M has become the predominant ESBL type in Glasgow, Scotland. The PFGE results show that four different CTX-M groups appear to be circulating in the community and within all four hospitals in the locality. There is little correlation between strain genotype and CTX-M group, thus it is unlikely that cross-infection alone is the driver. It is possible that plasmid migration of CTX-M genes within the E. coli population is occurring.

Background: The aim of this study was to determine if ertapenem (ERT) has the potency to induce c... more Background: The aim of this study was to determine if ertapenem (ERT) has the potency to induce carbapenem resistance in gram-negative bacteria, especially non-fermenters, in hospitals. Methods: Matched gram-negative bacterial isolates, responsible for hospital-acquired infections in 2007, were collected from the Freeman Hospital, Newcastle, (FHN) from wards where ERT was given and the Edinburgh Royal Infirmary (ERI) where meropenem (MERO) was the only carbapenem used. MICs of the carbapenems were determined by the agar dilution method following the CLSI guidelines. Single-step challenge experiments were performed with ERT and MERO; viable titres and antibiotic resistance levels (population analysis) for each strain were determined by plating diluted cultures onto IST agar plates containing concentrations of ERT and MERO at 1/4, 1/2, 1, 2, and 4x MIC. Surviving colonies were counted after overnight incubation at 37°C. A colony was purified, subcultured onto antibiotic-free media and...

Background: The degree of genetic flux within Acinetobacter baumannii may cause problems for geno... more Background: The degree of genetic flux within Acinetobacter baumannii may cause problems for genome-wide typing techniques. This study aimed to compare pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) schemes, and to evaluate the intrinsic blaOXA-51-like gene as a typing scheme candidate. Methods: A collection of 28 epidemiologically unrelated A. baumannii isolates were analysed by PFGE with restriction endonuclease Apa1, and results analysed using BioNumerics version 4 software. The gltA, rpoD, gdhB, gyrB, recA, cpn60, gpi and blaOXA-51-like genes were amplified and sequenced. Sequences were analysed using Multalin software, and isolates assigned to sequence types. Analysis of MLST profiles, blaOXA-51-like genes, and selection pressures on the MLST loci and blaOXA-51-like genes were carried out using START2 and Minitab15 software. Results: Twenty-three novel alleles for the MLST loci and 13 novel sequence types were identified. Isolates containing the ...

Journal of Medical Microbiology, 2011

Journal of Chemotherapy, 2008

ABSTRACT Resistance to fluoroquinolones is rising worldwidein multidrug resistant (MDR) Enterobac... more ABSTRACT Resistance to fluoroquinolones is rising worldwidein multidrug resistant (MDR) Enterobacteriacae 1. It is usually caused by mutations in the chromosomal genes coding for type II topoisomerases 2 and by changes in the expression of efflux pumps and porins 3. In addition, qnr genes responsible for plasmid-mediated quinolone resistance have been found in clinical isolates of Enterobacteriaceae 4. Recently, two new mechanisms of transferable quinolone resistance were reported, the cr variant of aac(6`)-Ib, which encodes an aminoglycoside acetyltransferase that confers reduced susceptibility to ciprofloxacin 5, and QepA as a plasmid-mediated efflux pump 6. In Scotland ESBLs are more prevalent among Klebsiella than other genera and more prevalent among K. pneumoniae than K. oxytoca.

Journal of Antimicrobial Chemotherapy, 2004

for non-nucleoside reverse transcriptase inhibitor resistance due to the low genetic barrier to r... more for non-nucleoside reverse transcriptase inhibitor resistance due to the low genetic barrier to resistance and relatively preserved fitness of non-nucleoside reverse transcriptase inhibitor-resistant virus. 9 While the relationship between adherence and resistance may be complex, we want to be completely clear that we are not suggesting that good adherence is bad. Even with early HAART, every 10% improvement in adherence was associated with a 20% decrease in the risk of progression to AIDS and death. 10,11 Disease progression was slowed or halted in many highly adherent individuals who developed resistance on early HAART. Individuals who took too little of their medication to create drug resistance, in contrast, suffered the natural history of untreated HIV infection. Because of the unfortunate manner in which partially suppressive HAART became available in many western countries, we now have large populations of maximally adherent patients with highly resistant HIV. The goal now is to define optimal strategies for such patients while working to prevent this from happening in the future.

Journal of clinical microbiology, 2010

This study used a diverse collection of epidemiologically unrelated Acinetobacter baumannii isola... more This study used a diverse collection of epidemiologically unrelated Acinetobacter baumannii isolates to compare the robustness of a multilocus sequence typing (MLST) scheme, based on conserved regions of seven housekeeping genes, gltA, gdhB, recA, cpn60, rpoD, gyrB, and gpi, with that of sequence-based typing of bla(OXA-51-like) genes (SBT-bla(OXA-51-like) genes). The data obtained by analysis of MLST and SBT-bla(OXA-51-like) genes were compared to the data generated by pulsed-field gel electrophoresis (PFGE). The topologies of the phylogenetic trees generated for the gyrB and gpi genes showed evidence of recombination and were inconsistent with those of the trees generated for the other five genes. MLST identified 24 sequence types (STs), of which 19 were novel, and 5 novel alleles. Clonality was demonstrated by eBURST analysis and standardized index of association values of >1 (P < 0.001). MLST data revealed that all isolates harboring the major bla(OXA-51-like) alleles OXA-...

Acinetobacter spp, particularly A. baumannii, are implicated in a wide spectrum of nosocomial inf... more Acinetobacter spp, particularly A. baumannii, are implicated in a wide spectrum of nosocomial infections, including bacteraemia, secondary meningitis, and urinary tract infections, but their most important role seems to be as agents of nosocomial pneumonia. Until 1988, the new fluorinated quinolones showed very good activity against Acinetobacter strains. However, reports of a high prevalence of fluoroquinolone resistance among Acinetobacter isolates have appeared. Therefore, understanding the mechanisms by which this phenomenon occurs in this pathogen is important. The two target proteins of the quinolones are the DNA gyrase (topoisomerase II) and topoisomerase IV. Studies with clinical isolates of A. baumannii have shown that mutations in the gyrA and parC genes were likely to be the major mechanisms of resistance. However, alteration in drug permeability or drug efflux could also contribute to quinolone resistance in A. baumannii. Initially, the purpose of this thesis is to compa...

Journal of Chemotherapy, 2012

Journal of Chemotherapy, 2008

VRE) 9 , extended-spectrum beta-lactamases (ESBL) Klebsiella pneumoniae and Enterobacter spp 10,1... more VRE) 9 , extended-spectrum beta-lactamases (ESBL) Klebsiella pneumoniae and Enterobacter spp 10,11 , multidrug-resistant (MDR) Pseudomonas aeruginosa 12 and MDR Acinetobacter baumannii 13. Infections caused by resistant non-fermenting bacteria, mainly, P. aeruginosa and A. baumannii, are difficult to treat because resistance to carbapenems, which in many cases represent the final treatment option, has been increasing worldwide 14,15. The aim of the present work was to investigate possible indications of epidemiological relationships be

Reviews in Medical Microbiology, 2007

ABSTRACT The extended-spectrum β-lactamases have evolved owing to the extensive use of the oxyimi... more ABSTRACT The extended-spectrum β-lactamases have evolved owing to the extensive use of the oxyimino-cephalosporins, and have greatly reduced the treatment options for serious infections. Acinetobacter baumannii is becoming an increasingly important multiresistant nosocomial pathogen due to the carriage of class D OXA-type β-lactamases. The OXA-23-like, OXA-40-like and OXA-58-like β-lactamases confer carbapenem resistance and are increasingly being found in association with a diversity of mobile genetic elements. High prevalence of OXA-40-like enzymes on the Iberian Peninsula, OXA-58-like enzymes across Europe and very high prevalence of OXA-23-like enzymes in South America and Asia are of concern. The intrinsic OXA-51-like enzymes of A. baumannii may confer carbapenem resistance when overexpressed, and form a large enzyme family. Similar patterns are beginning to be seen for the OXA-type β-lactamases, which were previously seen in the emergence of the extended-spectrum β-lactamases, the continuation of which would pose a grave threat to the antibiotic era.

The Journal of antimicrobial chemotherapy, 2010

The detection in Acinetobacter genospecies 3 isolates of OXA-type carbapenemases, resulting in re... more The detection in Acinetobacter genospecies 3 isolates of OXA-type carbapenemases, resulting in reduced susceptibility to carbapenem antibiotics, is increasingly reported. We identified an Acinetobacter genospecies 3 isolate carrying the gene for OXA-58 and aimed to resolve the genetic environment surrounding the bla(OXA-58) gene.

International journal of antimicrobial agents, 2011

High prevalence of unrelated multidrug-resistant Acinetobacter baumannii isolates in Pakistani mi... more High prevalence of unrelated multidrug-resistant Acinetobacter baumannii isolates in Pakistani military hospitals Sir, Nosocomial infections with multidrug-resistant (MDR) Acinetobacter baumannii are an increasing problem worldwide, with the emergence of carbapenem resistance conferred by acquired OXAtype carbapenemases such as the OXA-23 and OXA-58 families of particular concern. Frequently both bla OXA-23 and bla OXA-58 are identified in association with insertion sequences (IS), responsible for the mobilisation and expression of resistance genes. The transposons Tn2006, comprising the bla OXA-23 gene bracketed by two ISAba1 elements, and Tn2008, comprising a single ISAba1 element upstream of the bla OXA-23 gene, have been found in multiple globally distributed locations and are likely partially responsible for the increasing prevalence of the bla OXA-23 gene [1]. Despite high levels of carbapenem resistance in Pakistan [2], molecular surveillance studies are scarce for the region. The aim of this study was to examine the antimicrobial resistance properties of A. baumannii isolates from Pakistan, with a particular focus on carbapenem resistance. Twenty clinical bacterial isolates obtained over 2 months from two military hospitals in Rawalpindi, Pakistan, were biochem

Clinical Microbiology and Infection, 2007

Journal of Antimicrobial Chemotherapy, 2011

To establish the molecular epidemiology and antimicrobial resistance pattern of extendedspectrum ... more To establish the molecular epidemiology and antimicrobial resistance pattern of extendedspectrum b-lactamase (ESBL)-producing Enterobacteriaceae harbouring bla CTX-M in Glasgow, Scotland. Methods: During a 12 week period, Enterobacteriaceae isolates obtained from urine samples were collected and susceptibility testing performed. Isolates were screened for the presence of bla CTX-M by multiplex PCR and selected Escherichia coli genes were subsequently sequenced. PFGE analysis was performed on selected E. coli isolates in order to identify clonal relationships. Results: There were 155 phenotypically confirmed non-duplicate Enterobacteriaceae isolates obtained from urine samples. bla CTX-M was identified in 131/155 (84.5%) of the ESBL-producing isolates, with CTX-M group 1 enzymes accounting for 103/131 (78.6%) of these. The remaining 24 isolates carried other bla CTX-M types, including CTX-M group 2, CTX-M group 9 and an unidentifiable combination designated CTX-M group G2/Gx. A sample of 46/97 (47.4%) CTX-M-positive E. coli isolates was chosen for PFGE and demographic information regarding the source of the isolates was collated. Eight E. coli clusters were identified by PFGE; however, they did not achieve the 85% cutoff to demonstrate clonality. Nitrofurantoin resistance was significantly greater in the E. coli isolates expressing a non-CTX-M group 1 ESBL when compared with the E. coli isolates expressing a CTX-M group 1 ESBL. Conclusions: As seen in other British studies, bla CTX-M has become the predominant ESBL type in Glasgow, Scotland. The PFGE results show that four different CTX-M groups appear to be circulating in the community and within all four hospitals in the locality. There is little correlation between strain genotype and CTX-M group, thus it is unlikely that cross-infection alone is the driver. It is possible that plasmid migration of CTX-M genes within the E. coli population is occurring.

Background: The aim of this study was to determine if ertapenem (ERT) has the potency to induce c... more Background: The aim of this study was to determine if ertapenem (ERT) has the potency to induce carbapenem resistance in gram-negative bacteria, especially non-fermenters, in hospitals. Methods: Matched gram-negative bacterial isolates, responsible for hospital-acquired infections in 2007, were collected from the Freeman Hospital, Newcastle, (FHN) from wards where ERT was given and the Edinburgh Royal Infirmary (ERI) where meropenem (MERO) was the only carbapenem used. MICs of the carbapenems were determined by the agar dilution method following the CLSI guidelines. Single-step challenge experiments were performed with ERT and MERO; viable titres and antibiotic resistance levels (population analysis) for each strain were determined by plating diluted cultures onto IST agar plates containing concentrations of ERT and MERO at 1/4, 1/2, 1, 2, and 4x MIC. Surviving colonies were counted after overnight incubation at 37°C. A colony was purified, subcultured onto antibiotic-free media and...

Background: The degree of genetic flux within Acinetobacter baumannii may cause problems for geno... more Background: The degree of genetic flux within Acinetobacter baumannii may cause problems for genome-wide typing techniques. This study aimed to compare pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) schemes, and to evaluate the intrinsic blaOXA-51-like gene as a typing scheme candidate. Methods: A collection of 28 epidemiologically unrelated A. baumannii isolates were analysed by PFGE with restriction endonuclease Apa1, and results analysed using BioNumerics version 4 software. The gltA, rpoD, gdhB, gyrB, recA, cpn60, gpi and blaOXA-51-like genes were amplified and sequenced. Sequences were analysed using Multalin software, and isolates assigned to sequence types. Analysis of MLST profiles, blaOXA-51-like genes, and selection pressures on the MLST loci and blaOXA-51-like genes were carried out using START2 and Minitab15 software. Results: Twenty-three novel alleles for the MLST loci and 13 novel sequence types were identified. Isolates containing the ...

Journal of Medical Microbiology, 2011

Journal of Chemotherapy, 2008

ABSTRACT Resistance to fluoroquinolones is rising worldwidein multidrug resistant (MDR) Enterobac... more ABSTRACT Resistance to fluoroquinolones is rising worldwidein multidrug resistant (MDR) Enterobacteriacae 1. It is usually caused by mutations in the chromosomal genes coding for type II topoisomerases 2 and by changes in the expression of efflux pumps and porins 3. In addition, qnr genes responsible for plasmid-mediated quinolone resistance have been found in clinical isolates of Enterobacteriaceae 4. Recently, two new mechanisms of transferable quinolone resistance were reported, the cr variant of aac(6`)-Ib, which encodes an aminoglycoside acetyltransferase that confers reduced susceptibility to ciprofloxacin 5, and QepA as a plasmid-mediated efflux pump 6. In Scotland ESBLs are more prevalent among Klebsiella than other genera and more prevalent among K. pneumoniae than K. oxytoca.

Journal of Antimicrobial Chemotherapy, 2004

for non-nucleoside reverse transcriptase inhibitor resistance due to the low genetic barrier to r... more for non-nucleoside reverse transcriptase inhibitor resistance due to the low genetic barrier to resistance and relatively preserved fitness of non-nucleoside reverse transcriptase inhibitor-resistant virus. 9 While the relationship between adherence and resistance may be complex, we want to be completely clear that we are not suggesting that good adherence is bad. Even with early HAART, every 10% improvement in adherence was associated with a 20% decrease in the risk of progression to AIDS and death. 10,11 Disease progression was slowed or halted in many highly adherent individuals who developed resistance on early HAART. Individuals who took too little of their medication to create drug resistance, in contrast, suffered the natural history of untreated HIV infection. Because of the unfortunate manner in which partially suppressive HAART became available in many western countries, we now have large populations of maximally adherent patients with highly resistant HIV. The goal now is to define optimal strategies for such patients while working to prevent this from happening in the future.

Journal of clinical microbiology, 2010

This study used a diverse collection of epidemiologically unrelated Acinetobacter baumannii isola... more This study used a diverse collection of epidemiologically unrelated Acinetobacter baumannii isolates to compare the robustness of a multilocus sequence typing (MLST) scheme, based on conserved regions of seven housekeeping genes, gltA, gdhB, recA, cpn60, rpoD, gyrB, and gpi, with that of sequence-based typing of bla(OXA-51-like) genes (SBT-bla(OXA-51-like) genes). The data obtained by analysis of MLST and SBT-bla(OXA-51-like) genes were compared to the data generated by pulsed-field gel electrophoresis (PFGE). The topologies of the phylogenetic trees generated for the gyrB and gpi genes showed evidence of recombination and were inconsistent with those of the trees generated for the other five genes. MLST identified 24 sequence types (STs), of which 19 were novel, and 5 novel alleles. Clonality was demonstrated by eBURST analysis and standardized index of association values of >1 (P < 0.001). MLST data revealed that all isolates harboring the major bla(OXA-51-like) alleles OXA-...

Acinetobacter spp, particularly A. baumannii, are implicated in a wide spectrum of nosocomial inf... more Acinetobacter spp, particularly A. baumannii, are implicated in a wide spectrum of nosocomial infections, including bacteraemia, secondary meningitis, and urinary tract infections, but their most important role seems to be as agents of nosocomial pneumonia. Until 1988, the new fluorinated quinolones showed very good activity against Acinetobacter strains. However, reports of a high prevalence of fluoroquinolone resistance among Acinetobacter isolates have appeared. Therefore, understanding the mechanisms by which this phenomenon occurs in this pathogen is important. The two target proteins of the quinolones are the DNA gyrase (topoisomerase II) and topoisomerase IV. Studies with clinical isolates of A. baumannii have shown that mutations in the gyrA and parC genes were likely to be the major mechanisms of resistance. However, alteration in drug permeability or drug efflux could also contribute to quinolone resistance in A. baumannii. Initially, the purpose of this thesis is to compa...

Journal of Chemotherapy, 2012

Journal of Chemotherapy, 2008

VRE) 9 , extended-spectrum beta-lactamases (ESBL) Klebsiella pneumoniae and Enterobacter spp 10,1... more VRE) 9 , extended-spectrum beta-lactamases (ESBL) Klebsiella pneumoniae and Enterobacter spp 10,11 , multidrug-resistant (MDR) Pseudomonas aeruginosa 12 and MDR Acinetobacter baumannii 13. Infections caused by resistant non-fermenting bacteria, mainly, P. aeruginosa and A. baumannii, are difficult to treat because resistance to carbapenems, which in many cases represent the final treatment option, has been increasing worldwide 14,15. The aim of the present work was to investigate possible indications of epidemiological relationships be