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ABSTRACT: Bacterial resistance to antimicrobial agents is increasing. Complex resistant mechanisms have resulted in a wide spectrum of species and strains with multidrug-resistant patterns. In addition to the production of extended-spectrum-β-lactamases (ESBLs), Gram-negative rods have acquired the capacity to hydrolyze carbapenem antibiotics by means of carbapenemases. The enzyme that has gained the most publicity recently is the New Delhi metallo-β-lactamase (NDM-1). This enzyme and others are now spreading from their homeland on the Indian subcontinent to other continents, primarily via medical tourists. This spread contributes to be a global threat in an era when no potent antibiotics are expected to be developed. Patients coming from countries where antimicrobial use is not restricted, such as Iraq, may harbor similar organisms. Reports from the Middle East and Arabian countries describing the occurrence of carbapenem-resistant Enterobacteriaceae are rare. In this communication, an update on the epidemiology, prevalence and mechanisms of carbapenem-resistant Enterobacteriaceae in Lebanon and the surrounding region will be addressed in addition to the detection methods and required infection control practices.
Journal of infection and public health. 06/2012; 5(3):233-43.
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ABSTRACT: Carbapenem resistance has been encountered globally with poor outcome of infected patients. NDM-1 (New Delhi metallo-beta-lactamase) gene containing organisms have emerged and are now spreading in all continents. This is the first report of Iraqi patients referred to Lebanon from whom carbapenem resistant Enterobacteriaceae were recovered. The genes involved in carbapenem resistance were bla-OXA-48 and the novel NDM-1. This report highlights the alarming introduction of such resistance among Enterobacteriaecae to this country.
The Journal of Infection in Developing Countries 01/2012; 6(5):457-61. · 1.19 Impact Factor
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ABSTRACT: The spectrum of infections with Nocardia spp. is heterogeneous. It has classically been associated with lung, brain, or skin involvement. We describe an unusual presentation of Nocardia asiatica (N. asiatica) in an Iraqi patient with myasthenia gravis suffering from a disseminated infection and presenting with an anterior mediastinal cystic mass. N. asiatica has only been three times described outside Japan and Thailand, and the rarity of this entity deserves this communication.
Case reports in infectious diseases. 01/2012; 2012:325767.
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Nedal Taha, George F Araj,
Rima H Wakim,
Souha S Kanj,
Zeina A Kanafani,
Ahmad Sabra,
Marie-Therese Khairallah,
Farah J Nassar,
Marwa Shehab,
Maysa Baroud,
Ghassan Dbaibo,
Ghassan M Matar
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ABSTRACT: This study determined macrolide resistance genotypes in clinical isolates of Streptococcus pneumoniae from multiple medical centers in Lebanon and assessed the serotype distribution in relation to these mechanism(s) of resistance and the source of isolate recovery.
Forty four macrolide resistant and 21 macrolide susceptible S. pneumoniae clinical isolates were tested for antimicrobial susceptibility according to CLSI guidelines (2008) and underwent molecular characterization. Serotyping of these isolates was performed by Multiplex PCR-based serotype deduction using CDC protocols. PCR amplification of macrolide resistant erm (encoding methylase) and mef (encoding macrolide efflux pump protein) genes was carried out.
Among 44 isolates resistant to erythromycin, 35 were resistant to penicillin and 18 to ceftriaxone. Examination of 44 macrolide resistant isolates by PCR showed that 16 isolates harbored the erm(B) gene, 8 isolates harbored the mef gene, and 14 isolates harbored both the erm(B) and mef genes. There was no amplification by PCR of the erm(B) or mef genes in 6 isolates. Seven different capsular serotypes 2, 9V/9A,12F, 14,19A, 19F, and 23, were detected by multiplex PCR serotype deduction in 35 of 44 macrolide resistant isolates, with 19F being the most prevalent serotype. With the exception of serotype 2, all serotypes were invasive. Isolates belonging to the invasive serotypes 14 and 19F harbored both erm(B) and mef genes. Nine of the 44 macrolide resistant isolates were non-serotypable by our protocols.
Macrolide resistance in S. pneumoniae in Lebanon is mainly through target site modification but is also mediated through efflux pumps, with serotype 19F having dual resistance and being the most prevalent and invasive.
Annals of Clinical Microbiology and Antimicrobials 01/2012; 11:2. · 2.64 Impact Factor
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George F Araj
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ABSTRACT: The persistent worldwide prevalence of human brucellosis causes serious public health concerns and economic loss to communities. The multisystem involvement and the protean and unusual clinical presentations of the disease pose significant diagnostic challenges. The clinical features are non-specific and can overlap with a wide spectrum of other infectious and non-infectious diseases, leading to brucellosis being labelled the 'disease of mistakes'. Protracted chronicity and serious complications can result and mislead physicians onto a path of costly laboratory and radiological investigations. To reach a diagnosis clinicians must use a wide range of non-specific routine haematological and biochemical tests in addition to Brucella-specific assays. The latter are microbiological (culture), serological (e.g. slide or tube agglutination, Coombs test, immunocapture agglutination, Brucellacapt, immunochromatographic lateral flow, enzyme-linked immunosorbent assays and the indirect fluorescent antibody test) and molecular (e.g. polymerase chain reaction (PCR) and real-time PCR). Each of these tests has advantages and limitations, and thus requires careful interpretation. Since brucellosis can have several presentations and phases (acute, subacute, chronic, relapsed, active and inactive), the search for reliable, discriminatory diagnostic and prognostic markers, especially for monitoring disease evolution, are ongoing. Although much progress has been made, further challenges remain to the accurate diagnosis of this historic but still common global zoonotic disease.
International journal of antimicrobial agents 11/2010; 36 Suppl 1:S12-7. · 3.03 Impact Factor
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ABSTRACT: Subacute and chronic spondylodiscitis can be caused by a wide spectrum of infectious aetiologies including Mycobacterium tuberculosis, Brucella spp. and a variety of fungi including Aspergillus spp., Candida spp. and Cryptococcus neoformans. Knowledge of the local epidemiology and prior exposure might suggest the aetiology. Non-invasive diagnostic approaches, such as blood culture or antibody titres in the case of Brucella or antigen detection in the case of fungal infections, can be helpful in reaching the diagnosis. However, direct aspiration or tissue biopsy is usually necessary to identify the causative organism. Specimens are usually sent for pathology, special stains, cultures and, when indicated, molecular analysis. To minimise morbidity and mortality, antibiotic treatment should be initiated promptly directed against the suspected organism, and later adjusted according to the confirmed aetiology. Surgical treatment is reserved for recurrent infection, unstable spinal segment or marked kyphosis in the face of any neurological deficits and uncontrollable pain. Surgical approaches are dictated by the anatomic location of the offending lesion. Once medical treatment fails and surgery becomes warranted, we advocate the use of a two-stage surgical treatment for non-fixed kyphosis and a three-stage operation for fixed kyphosis.
International journal of antimicrobial agents 08/2010; 36(2):99-105. · 3.03 Impact Factor
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ABSTRACT: The frequency of transfer of genes encoding resistance to antimicrobial agents was determined by conjugation in ESBL-producing and/or fluoroquinolone or aminoglycoside resistant Enterobacteriaceae clinical isolates at a tertiary care center in Lebanon. In addition, the role of tra genes encoding transferases in mediating conjugation was assessed.
Conjugation experiments were done on 53 ESBL-producing and/or fluoroquinolone resistant E. coli and K. pneumoniae and ESBL-producing S. sonnei isolates. Antimicrobial susceptibility testing on parent and transconjugant isolates, and PCR amplifications on plasmid extracts of the resistance-encoding genes: blaCTX-M-15 with the ISEcp1 insertion sequence, the aac(6')-lb-cr and qnrS genes, as well as tra encoding transferases genes were done. Random amplified polymorphic DNA (RAPD) analysis was performed to demonstrate whether conjugative isolates are clonal and whether they are linked epidemiologically to a particular source.
Antimicrobial susceptibility testing on transconjugants revealed that 26 out of 53 (49%) ESBL-producing Enterobacteriaceae were able to transfer antimicrobial resistance to the recipients. Transfer of high-level resistance to the transconjugants encoded by the blaCTX-M-15 gene downstream the ISEcp1 insertion sequence against 3rd generation cephalosporins, and of low-level resistance against ciprofloxacin, and variable levels of resistance against aminoglycosides encoded by aac(6')-lb-cr gene, were observed in transconjugants. tra encoding transferase genes were detected exclusively in conjugative isolates.
In conclusion, the frequency of transfer of antimicrobial resistance in non clonal Enterobacteriaceae at the tertiary care center by conjugation was 49%. Conjugation occurred in isolates expressing the tra encoding transferase genes. Multiple conjugative strains harboring the plasmid encoded antimicrobial resistant genes were circulating in the medical center. Molecular epidemiology analysis showed that conjugative isolates are neither clonal nor linked to a particular site and transfer of antimicrobial resistance is by horizontal transfer of plasmids.
Annals of Clinical Microbiology and Antimicrobials 01/2010; 9:19. · 2.64 Impact Factor
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ABSTRACT: The global emergence of Streptococcus pneumoniae resistance to fluoroquinolones is alarming and has grown to be a cause for significant concern worldwide. We report the first three cases of levofloxacin resistant S. pneumoniae isolates in a tertiary medical center in Beirut, Lebanon. Judicious use of antimicrobial agents is imperative to limit the spread of such resistant strains.
Journal of infection and public health. 01/2010; 3(3):113-7.
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ABSTRACT: We describe a rare case of tricuspid valve endocarditis caused by Pasteurella multocida in an elderly woman with no previous history of valvular heart disease. Risk factors included contact with animals and old age. The patient was treated successfully with five days of intravenous ampicillin followed by four weeks of oral ciprofloxacin.
International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 02/2009; 13(5):e267-9. · 2.17 Impact Factor
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ABSTRACT: We report a fatal case of disseminated Mycobacteriumsimiae infection in an immunocompetent elderly man with fever of unknown origin. The diagnosis was based on culture isolation of non-tuberculous mycobacteria from cerebrospinal fluid and bronchoalveolar lavage. Both culture isolates were identified as M. simiae by 16S rRNA gene sequencing.
International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 02/2009; 13(5):e286-7. · 2.17 Impact Factor
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ABSTRACT: Emergence of extended-spectrum beta-lactamases (ESBLs) in Shigella species imparting resistance to third-generation cephalosporins is a growing concern worldwide. The aim of this study is to molecularly characterize the newly emerging beta-lactam resistant Shigella sonnei, specifically ESBLs in Lebanon, and compare them to beta-lactam sensitive isolates.
We compared five beta-lactam-resistant S. sonnei isolates to six isolates susceptible to beta-lactams. Presence of ESBLs was established by the combination disk method. PCR amplification and sequence analysis of the beta-lactamase-encoding genes, along with other antimicrobial resistance genes, were performed. The localization of beta-lactamase genes was established by conjugation experiments. Beta-lactamase gene transcription levels were determined by real-time RT-PCR. Molecular typing was performed by pulsed-field gel electrophoresis (PFGE).
Four of five beta-lactam resistant isolates were extended spectrum beta-lactamase producers. These harbored the bla-CTX-M-15 gene borne on a 70 Kb plasmid and class 2 integron genes on their chromosomes. The bla-CTX-M-15 gene was flanked by an insertion element ISEcp1. A chromosomal bla-TEM-1 gene was detected in one beta-lactam resistant Shigella isolate and two of the ESBL producing isolates. The bla-CTX-M-15 gene transcription levels were increased in EBSL isolates exposed to subinhibitory concentrations of ceftazidime. PFGE analysis revealed that the four bla-CTX-M-15 positive isolates were nonclonal but two of them shared genotypes with -lactam susceptible isolates.
Dissemination of broad-spectrum beta-lactam resistance in Shigella sonnei is mediated by bla-CTX-M-15 through horizontal plasmid transfer rather than by clonal spread of the resistant isolates. Expression of this gene is further induced in the presence of ceftazidime.
The Journal of Infection in Developing Countries 01/2009; 3(4):300-5. · 1.19 Impact Factor
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ABSTRACT: The antimicrobial susceptibility profiles of 76 Streptococcus agalactiae (Group B Streptococci [GBS]) isolates from vaginal specimens of pregnant women near term were correlated to their genotypes generated by Random Amplified Polymorphic DNA analysis and their virulence factors encoding genes cylE, lmb, scpB, rib, and bca by PCR. Based on the distribution of the susceptibility patterns, six profiles were generated. RAPD analysis detected 7 clusters of genotypes. The cylE gene was present in 99% of the isolates, the lmb in 96%, scpB in 94.7%, rib in 33%, and bca in 56.5% of isolates. The isolates demonstrated a significant correlation between antimicrobial resistance and genotype clusters denoting the distribution of particular clones with different antimicrobial resistance profiles, entailing the practice of caution in therapeutic options. All virulence factors encoding genes were detected in all seven genotypic clusters with rib and bca not coexisting in the same genome.
International Journal of Microbiology 01/2009; 2009:796512.
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ABSTRACT: Brucellosis remains an important anthropozoonosis worldwide. Brucella species are genetically homogeneous, and thus, the typing of Brucella species for epidemiological purposes by conventional molecular typing methods has remained elusive. Although many methods could segregate isolates into the phylogenetically recognized taxa, limited within-species genetic diversity has been identified. Recently, multilocus variable-number tandem-repeat analysis (MLVA) was found to have a high degree of resolution when it was applied to collections of Brucella isolates from geographically widespread locations, and an assay comprising 16 such loci (MLVA-16) was proposed. This scheme includes eight minisatellite loci (panel 1) and eight microsatellites (panel 2, which is subdivided into panels 2A and 2B). The utility of MLVA-16 for the subtyping of human Brucella isolates from geographically restricted regions needs to be further evaluated, and genotyping databases with worldwide coverage must be progressively established. In the present study, MLVA-16 was applied to the typing of 42 human Brucella isolates obtained from 41 patients recovered from 2002 to 2006 at a tertiary-care center in Lebanon. All isolates were identified as Brucella melitensis by MLVA-16 and were found to be closely related to B. melitensis isolates from neighboring countries in the Middle East when their genotypes were queried against those in the web-based Brucella2007 MLVA database (http://mlva.u-psud.fr/). Panel 2B, which comprised the most variable loci, displayed a very high discriminatory power, while panels 1 and 2A showed limited diversity. The most frequent genotype comprised seven isolates obtained over 7 weeks in 2002, demonstrating an outbreak from a common source. Two isolates obtained from one patient 5 months apart comprised another genotype, indicating relapsing disease. These findings confirm that MLVA-16 has a good discriminatory power for species determination, typing of B. melitensis isolates, and inferring their geographical origin. Abbreviated panel 2B could be used as a short-term epidemiological tool in a small region of endemicity.
Journal of clinical microbiology 11/2008; 46(12):3935-40. · 4.16 Impact Factor
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ABSTRACT: The lack of data from the Middle East warranted studying tigecycline in vitro activity in Lebanon against consecutive multidrug-resistant (MDR) bacteria, including extended-spectrum beta-lactamases producing clinical isolates of Escherichia coli (n = 150), Klebsiella pneumoniae (n = 100), and Acinetobacter spp. (n = 64) using the standard disk diffusion method. Tigecycline-resistant and intermediate findings were as follows: E. coli, 0% and 0%; K. pneumoniae, 3% and 16%; and Acinetobacter spp., 0% and 2%. These values were substantially lower than those determined for amikacin, gentamicin, tobramycin, ciprofloxacin, piperacillin/tazobactam, amoxicillin/clavulanic acid, and trimethoprim/sulfamethoxazole. This study demonstrates the excellent activity of tigecycline against the increasingly encountered MDR bacteria in Lebanon. The introduction of this effective and viable drug for the initial or recommended treatment of serious infections caused by such highly resistant pathogens is an asset for patients in this country and elsewhere.
Diagnostic Microbiology and Infectious Disease 10/2008; 62(4):411-5. · 2.53 Impact Factor
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International Journal of Infectious Diseases 12/2007; 11(6):554-6. · 1.94 Impact Factor
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ABSTRACT: This study aimed at developing a real-time polymerase chain reaction (PCR) assay for the rapid diagnosis of human brucellosis on clinical specimens. Three assays with hybridization probe detection on the LightCycler instrument were developed and compared targeting the 16S-23S internal transcribed spacer region (ITS) and the genes encoding for omp25 and omp31. All assays showed 100% analytical sensitivity and 100% specificity when tested on 28 consecutive clinical isolates of Brucella sp. and 19 clinical isolates of common Gram-negative and Gram-positive bacterial pathogens, respectively. The ITS assay was the most sensitive with a limit of detection of 2 genome equivalents per PCR reaction. This assay was then clinically validated prospectively with 354 samples (351 whole blood samples and 3 paraffin-embedded tissues) collected from 340 patients, 24 samples from patients with active brucellosis including 2 relapsing cases, 31 with treated brucellosis, and 299 seronegative patients where brucellosis was initially suspected. The clinical sensitivity, specificity, and positive and negative predictive values of the ITS assay were 66.7%, 99.7%, 94.1%, and 97.6%, compared with culture at 77%, 100%, 100%, and 97.3%, respectively. The difference in sensitivity between culture and ITS-PCR was not statistically significant (P = 0.71). Both relapsing cases were PCR positive. Treated patients were PCR negative. All 3 assays were positive on tissue samples, but the omp25 and omp31 assays did not detect Brucella sp. DNA in blood samples. Because omp31 is not present in Brucella abortus, these data indicate that the 28 tested isolates are most likely Brucella melitensis. ITS-PCR is rapid and could augment the clinical laboratory diagnosis of human brucellosis.
Diagnostic Microbiology and Infectious Disease 10/2007; 59(1):23-32. · 2.53 Impact Factor
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ABSTRACT: Previous studies from Lebanon have shown Gram-negative organisms to be the predominant agents in febrile neutropenic patients. The objective of this study was to evaluate the most current epidemiological trends among patients with neutropenic fever.
This prospective observational cohort study, the largest to date in the country, was conducted at the American University of Beirut Medical Center between January 2001 and December 2003, with the objective of describing the characteristics of patients with neutropenic fever and to assess temporal trends.
We included 177 episodes of neutropenic fever. The most common underlying malignancy was lymphoma (42.4%). Gastrointestinal and abdominal infections were predominant (31.6%) and 23.7% of cases represented fever of unknown origin. Gram-negative organisms were responsible for 78.8% (26/33) of bloodstream infections compared to 33.3% (11/33) with Gram-positive organisms. The in-hospital mortality rate in this study (12.1%) was considerably lower than in previous years.
Gram-negative organisms are persistently predominant in our center. In a developing country like Lebanon with limited resources, lower mortality rates commensurate with worldwide reports were successfully achieved in this high-risk patient population. Protocols and guidelines should be adapted to the characteristics of individual institutions to ensure delivery of appropriate care to febrile neutropenic patients.
International Journal of Infectious Diseases 10/2007; 11(5):450-3. · 1.94 Impact Factor
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ABSTRACT: To evaluate the efficacy of a 7-day regimen of gatifloxacin (400 mg daily), amoxicillin (1 g twice a day), and rabeprazole (20 mg twice a day) in the secondary eradication of Helicobacter pylori infection.
Eligible patients with persistent infection following one or more conventional clarithromycin-containing triple therapies were enrolled in this open-label trial. Eradication of infection was documented by (14)C-urea breath test a minimum of 4 weeks after therapy and 2 weeks off any acid suppressive therapy. Culture of H. pylori and in vitro susceptibility testing to amoxicillin, clarithromycin, and gatifloxacin was done in cases of failed eradication.
A total of 45 patients (22 females:23 males; mean age 44.5 +/- 13 years) were enrolled. Eradication occurred in 38 patients [both per-protocol (PP) and intention-to-treat analysis: 84.4%; 95% CI: 74-95%]. No significant adverse effects were reported. In vitro susceptibility testing showed no secondary resistance to gatifloxacin or amoxicillin in any of the seven nonresponders. Smoking, age, and sex were not predictors of potential eradication failure.
A 7-day regimen of gatifloxacin, rabeprazole, and amoxicillin is effective after failed eradication therapy for H. pylori and does not appear to result in secondary resistance. This combination is simple, well tolerated, and may lead to higher compliance and lower costs.
Helicobacter 09/2006; 11(4):231-6. · 3.15 Impact Factor
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ABSTRACT: A 2-step polymerase chain reaction (PCR) assay and random amplification of polymorphic DNA (RAPD) analysis, respectively, were assessed to identify coagulase-negative staphylococci organisms to the species level and to determine the strain diversity and spread of Staphylococcus epidermidis, the most frequently isolated species, in a medical center in Beirut, Lebanon. Our data indicated that PCR was faster and was more efficient in identifying S. epidermidis isolates than is conventional biochemical testing. RAPD analysis have shown that S. epidermidis strains were scattered across the different clinical services, demonstrating various clusters of infection in the medical center.
Infection Control and Hospital Epidemiology 08/2006; 27(7):781-3. · 3.67 Impact Factor
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ABSTRACT: PANBIO Brucella immunoglobulin G (IgG) and IgM enzyme-linked immunosorbent assays (ELISAs) were assessed against Brucella standard agglutination tube and Coombs tests. The sensitivities of ELISA IgG and IgM were 91% and 100%, respectively, while the specificity was 100% for both. These ELISAs are simple, rapid, and reliable for the diagnosis of human brucellosis.
Clinical and Diagnostic Laboratory Immunology 12/2005; 12(11):1334-5. · 2.51 Impact Factor
