Epidemiology, microbiological, clinical characteristics, and outcome of Burkholderia cepacia complex infections in non-cystic fibrosis adult patients from Qatar.

Objectives: Burkholderia species infections are associated with diverse and challenging clinical presentations because of distinct virulence and antimicrobial resistance factors. The study aims to evaluate the epidemiology, microbiological, and clinical outcomes of Burkholderia cepacia complex (Bcc) infections in non-cystic fibrosis (CF) patients from Qatar. Methods: A retrospective study was conducted on adult patients across all hospitals at Hamad Medical Corporation between January 2012 and December 2018 to evaluate clinically relevant Bcc in non-CF adult patients. Results: Over 7 years, 72 episodes of Burkholderia species infections were recorded, 64 were secondary to Bcc primarily affecting males (78.12%) with a mean age of 53 years, from the Middle and Southeastern region (92.2%) affected predominantly by diabetes mellitus (34.4%), chronic kidney (23.4%), coronary heart (20.3%), and hypertensive diseases (17.2%) while recent hospitalization and admission to critical care were evident in 45.3% and 93.8% of cases, respectively. Main infection sites were urinary (43.8%) and respiratory (29.7%) with associated bacteremia recorded in 26.6% of cases. Microbiological characteristics demonstrated high-level resistance profiles leading to delayed microbiological clearance in case of bacteremia (61%) and management with multiple therapeutic agents (range 4-6) resulting in disease resolution in 90.6% of cases with observed 30-day mortality of 7.8%. Conclusions: B. cepacia infections are infrequent, recorded mainly in middle-aged males with chronic comorbidities presenting as urinary, respiratory, and bacteremia associated with hospitalization, admission to critical care, and invasive procedures. High-level antimicrobial resistance is observed necessitating multiple therapeutic agents and suboptimal bacteriological clearance.

Cefepime-Induced Neutropenia: A Case Report and Literature Review.

Cefepime is a fourth-generation cephalosporin utilized in treatment of multiple Gram-negative and -positive infections. The current report presents a case of 50-year-old man admitted with epidural abscess who developed neutropenia after prolonged use of cefepime. The neutropenia developed after 24 days of cefepime treatment and resolved 4 days after cessation of cefepime. Assessment of the patient's profile indicated no other possible cause for neutropenia. A literature review was done, and is presented herein to compare and identify the pattern of cefepime-induced neutropenia in 15 patients. The data presented in this article highlight that despite its rarity, cefepime-induced neutropenia should be considered by clinicians when planning a prolonged course of cefepime.

Neurocysticercosis presenting with oculomotor nerve palsy: Case report and literature review.

Neurocysticercosis (NCC), a central nervous system infection caused by the cystic larvae of Taenia Solium, is endemic in many low-to-middle income countries. NCC is known to have a variety of presentations depending on the size and site of involvement including chronic headaches, seizures, hydrocephalus, and ischemic insults. NCC has also been rarely associated with cranial nerve palsies. We report the case of a 26-year-old Nepalese lady who presented with isolated left-sided oculomotor nerve palsy and was found to have midbrain NCC. She was treated with anthelminthic agents and corticosteroids which led to clinical improvement. NCC can present with a variety of focal neurological syndromes. To the best of our knowledge, this is the first case report of NCC presenting with third cranial nerve palsy in the state of Qatar and the middle east. We also review the literature for other cases of NCC which presented with isolated oculomotor nerve palsy.

Endogenous endophthalmitis due to Serratia marcescens secondary to late-onset empyema Post-Cardiac surgery in an End-Stage renal disease patient on peritoneal dialysis.

Endogenous bacterial endophthalmitis results from bacterial seeding of the eye during bacteremia. A diagnosis of endogenous bacterial endophthalmitis requires clinical findings such as vitritis or hypopyon along with positive blood cultures. Serratia marcescens is the second most common pathogen causing hospital-acquired ocular infections. This report describes a case of endogenous bacterial endophthalmitis caused by S. marcescens in an older adult with end-stage renal disease (ESRD) on peritoneal dialysis, who had late-onset pleural empyema secondary to coronary artery bypass grafting (CABG). A 61-year-old gentleman presented with a two-day history of cloudy vision, black floaters, pain, swelling, and gradual vision loss in his right eye. There was no history of trauma, ocular surgeries, or previous similar episodes. He had myocardial infarction treated with CABG 3 months back. Examination showed a 3 mm hypopyon in the anterior chamber. He had classic signs of endophthalmitis with positive blood cultures for S. marcescens. He was treated with high-dose intravenous meropenem and intravitreal ceftazidime without vitrectomy. Endophthalmitis progressed to complete vision loss in his right eye, requiring evisceration. Endophthalmitis caused by S. marcescens is rare, but long-term outcomes can be severe, causing complete vision loss in about 60% of the patients. It is usually hospital-acquired, and the source can be late-onset empyema several months after cardiac surgery, in an immunocompromised patient. Systemic antibiotics should be supplemented with intravitreal agents with or without pars plana vitrectomy.

Microbiological and clinical characteristics of invasive Group B Streptococcal blood stream infections in children and adults from Qatar.

INTRODUCTION: Group B Streptococci (GBS) colonize almost one third of human gastrointestinal and genitourinary tracts, particularly in females. The aim of this study is to evaluate the epidemiology, microbiological characteristics, and clinical outcomes of invasive GBS disease in Qatar from all age groups. METHODS: A retrospective study was conducted on patients with confirmed GBS blood stream infections during the period between January 2015 and March 2019. Microbiological identification was performed using automated BD PhoenixTM system, while additional antimicrobial susceptibility tests were performed using E test and disc diffusion methods. RESULT: During the four years period, the incidence steadily rose from 1.48 to 2.09 cases per 100.000 population. Out of 196 confirmed cases of invasive GBS infections, the majority were females (63.7%, 125/196) of which 44.8% were pregnant and 53.6% were colonized. Three distinct affected age groups were identified: children ≤ 4 years of age (35.7%), young adults 25-34 (20.9%) and the elderly ≥ 65 year (17.4%). Presenting symptoms were mild with fever in 53% of cases while 89% of cases had Pitt bacteraemia score of ≤ 2. Isolates were universally sensitive to penicillin, ceftriaxone, and vancomycin at 100% but with significant resistance to erythromycin (49%) and clindamycin (28.6%) while 16.8% had inducible clindamycin resistance. Clinical outcomes showed cure rate of 87.25% with complications in (8.76%) and 4% mortality. CONCLUSION: There is a rising trend of Group B Streptococcal blood stream infections in Qatar with significantly high clindamycin and erythromycin resistance rates. Universal susceptibility rates were demonstrated for penicillin, ceftriaxone, and vancomycin.

HIV and AIDS-defining opportunistic illnesses in the state of Qatar: A cohort population-based retrospective study covering 17 years (2000-2016).

Background and introduction: Human immune deficiency virus (HIV) infection remains a major health problem since discovery of the virus in 1981. Globally, since introduction of antiretroviral therapy, AIDS-related mortality was reduced by 47% since 2010. Also, HIV-related opportunistic infections (OIs) became less common, especially with use of prophylaxis to prevent such infections. In this study, we aim to assess the incidence of HIV infection and related OIs in Qatar for 17-year period, and to assess the spectrum of these infections, risk factors and treatment outcomes. Methods: This is a retrospective cohort study for all HIV infected patients registered in the state of Qatar from 2000 to 2016. Incidence of HIV infection and related opportunistic illness was calculated per 100,000 population. Demographic and Clinical characteristic were compared between two groups of patients with and without opportunistic illness. Results: of 167 cases with HIV infection 54 (32.3%) had opportunistic illness. The average incidence rate of HIV infection over 17 years is 0.69 per 100,000 population, and the incidence rate for opportunistic illness is 0.27 per 100,000 population. The most common opportunistic illness is pneumocystis jirovecii pneumonia (PCP) which constituted 25% of cases, followed by cytomegalovirus (CMV) retinitis 7.2%, Tuberculosis 5.4%, Toxoplasmosis 4.2% and, less than 2% for each of Kaposi sarcoma, lymphoma and cryptococcal infection.The outcome of treatment of cases with opportunistic illness showed cure rates of 59.3%, one year relapse rates of 8.76% and overall, 90-day mortality of 3.7% however, 33.4% of patients left the country before completion of therapy.Most of our patients in both groups were of young age, majority males, and almost half of them were Qatari. The CD4 count, CD4%, CD4/CD8 ratio and viral load were statistically significant risk factors in cases with opportunistic illness with a p value < 0.05, however presence of comorbidities was lower in patients with opportunistic illness P value of 0.032. Conclusion: Qatar has a low prevalence rate for HIV infection and related opportunistic illness. Early diagnosis and use of antiretroviral therapy are important measures to decrease the rate of opportunistic illness.

A 5-year retrospective study of Actinomyces odontolyticus bacteremia in the state of Qatar, case series.

Introduction and importance: Manifestations of infection by A. odontolyticus include thoracic, abdominal, pelvic, and central nervous system disease. In the four decades following its isolation, more than 20 cases of invasive infections were reported in multiple geographic locations including the United States and Europe. As such, A. odontolyticus is an emerging bacterium and related research is encouraged for further characterization of its prevalence and clinical significance. Our case series represents the first case series about A. odontolyticus bacteremia in the state of Qatar. Methods: We are reporting 15 cases with isolated A. odontolyticus positive blood cultures at Hamad Medical Corporation, State of Qatar from 1/Jan/2016 to 1/Nov/2020. Electronic health records (EHR) of patients who were identified to have positive blood cultures were accessed and the demographics and other clinically related data were collected and mentioned in this manuscript, after obtaining the appropriate approval from the Corporation Medical Research Council (MRC). Outcomes: We are reporting 15 cases with isolated A. odontolyticus positive blood cultures at Hamad Medical Corporation, State of Qatar from 1/Jan/2016 to 1/Nov/2020. Conclusion: 12 of the 15 reported cases were considered significant and received a complete course of antimicrobial therapy. The patients presented with a wide variety of clinical pictures and were of variable age.

Actinomyces odontolyticus bacteraemia associated with cervical and mediastinal abscesses in an immunocompetent patient: First reported case in Qatar.

The Actinomyces bacteria are associated with cervicothoracic disease in immunocompromised patients; however, Actinomyces odontolyticus cervical infection with extensive spread to the mediastinum in a previously healthy patient was not reported before in Qatar. The patient underwent drainage of collections in synchrony with intravenous antibiotics and recovered with an excellent outcome.

The Role of Post-Bronchoscopy Sputum Examination in Screening for Active Tuberculosis.

Early diagnosis is a fundamental component of global tuberculosis control. The objective of this study was to evaluate the diagnostic yield of post-bronchoscopy sputum (PBS) testing as part of a tuberculosis diagnostic work-up. All new residents in the State of Qatar undergo a tuberculosis (TB) screening program. Those with abnormal chest radiology, negative sputum acid-fast bacilli (AFB) smears, and nucleic acid amplification testing (NAAT) for M. tuberculosis, undergo an additional bronchoscopic evaluation for TB. We prospectively enrolled individuals who were going to undergo bronchoscopy to provide two PBS samples for AFB smears and mycobacterial cultures between 18 September 2018 and 12 March 2021. A total of 495 individuals, with a median age of 31 years, were included. The majority of the patients were males (329, 66.5%). The most frequent country of origin was India (131, 26.5%) followed by the Philippines (123, 24.8%). The addition of PBS to bronchoalveolar lavage (BAL) testing allowed microbiological confirmation of tuberculosis in an additional 13 patients (3.9%), resulting in improved sensitivity (from 77.9% to 81.9%), negative predictive value (from 69.2% to 73.2%), and negative likelihood ratio (from 0.22 to 0.18). Where resources are available, the incorporation of routine PBS examination as part of tuberculosis diagnostic work-up can enhance the diagnostic yield.

Beware of the ambiguous enemy of multisystem inflammatory syndrome in adult (MIS-A) following Covid-19 infection or vaccination.

Multisystem Inflammatory Syndrome is a rare and novel clinical presentation described during the evolving COVID-19 pandemic. The condition is usually presenting as a sepsis-like syndrome leading to secondary multi-organ dysfunction post-COVID-19 infection. Although the syndrome has been mainly described in children, rare adults' form has been similarly described. We are describing a 37-year-old female patient presented with fever and neck pain after 1 month of a mild SARS-CoV-2 infection course and 10 days post her second COVID-19 vaccine. Examination demonstrated fever, hypotension, and hypoxemia, in addition to multiple tender cervical lymph nodes. Initial laboratory workup showed evidence of significant inflammation with raised markers, including C-reactive protein, ferritin, and interleukin-6. Extensive evaluation to rule out active infection was done, and all return negative, including repeat SARS-CoV-2 test. Furthermore, cardiac evaluation showed moderately reduced systolic ventricular function. Despite all negative test and supportive measures, the patient continued to deteriorate requiring critical care admission for ionotropic support, non-invasive ventilation in addition to presumptive broad-spectrum antimicrobial management. There was no significant improvement with supportive care until the presentation of multisystem involvement on in the context of a recent history of COVID 19 and negative infective screen was raised. The diagnosis of multisystem inflammatory syndrome-adult form (MIS-A) was embraced, and the patient was commenced on methylprednisolone leading to a dramatic resolution of symptoms both clinically and biochemically with stabilization of vital functions allowing for safe outcomes.

Primary mediastinal hydatidosis successfully treated with combined medical therapy and VATS (Video-assisted thoracoscopic surgery).

Mediastinal involvement of hydatidosis is rare even in endemic areas. Isolated mediastinal without lung or liver involvement is even less commonly reported. We present the case of a young gentleman who was diagnosed with primary mediastinal hydatidosis based on clinical, radiological and pathological criteria. He underwent successful resection of the lesion by VATS (Video-assisted thoracoscopic surgery) preceded by two weeks of medical treatment with albendazole and had an excellent outcome. To the best of our knowledge, this is the first reported case in the state of Qatar.

Drug-resistant tuberculosis: an experience from Qatar.

This study was conducted to evaluate the characteristics, treatment outcome and risk factors associated with 223 drug-resistant tuberculosis (DR-TB) cases in the State of Qatar. A descriptive records-based retrospective study was conducted on patients registered at Communicable Disease Centre (CDC), Qatar to all consecutive microbiologically confirmed tuberculosis cases for the period January 2010 - March 2015. Demographic, clinical data, drug-resistance pattern of isolated mycobacteria and treatment outcome was assessed for the patient who completed their treatment in Qatar. Of 3301 patients with positive M. tuberculosis culture were analyzed; 223 (6.7%) were resistant to at least one drug. The overall prevalence of multi-d rug resistant TB (MDR-TB) was 1.2% (n = 38) of patients. A former resident of Indian sub contents was the most common demographic characteristic observed (64.1%). The outcome of treatment was assessed for 85 resistant cases with follow-up after completion of treatment. Cure and relapse rates were 97.6%, and 2.4%, respectively. Drug-resistant TB in Qatar is influenced by migration where the patients were probably infected. Rapid sputum sampling performed in the early stages of the disease, patient isolation, and drug-susceptibility testing should be the standard of care.

Tuberculosis of pancreas, the first case reported from Qatar.

Despite the high prevalence of tuberculosis (TB) in developing countries, primary pancreatic TB is a rare entity. We present a case of pancreatic TB in an immunocompetent patient who was found to have pancreatic mass resembling malignancy. A 40-year-old Indian male presented to the medical emergency room with complaints of abdominal pain and fever for 2 weeks' duration. He had a history of unintentional weight loss of about 20 pounds in the past 2 months. There was no significant history of exposure to TB patient. Family history was unremarkable for any malignancy. On examination, the significant finding was epigastric tenderness. He was thoroughly investigated, his purified protein derivative and QuantiFERON were negative. Chest X-ray was unremarkable. Computed tomography scan abdomen was performed that revealed large heterogenous necrotic mass in the lesser sac likely arising from pancreatic body with possible infiltration of the stomach, left lobe of the liver and encasing celiac vessels and portal vein with multiple peripancreatic and retroperitoneal necrotic lymph nodes. Endoscopic ultrasound with fine-needle aspiration of pancreatic mass was done, biopsy specimen revealed the presence of inflammation with no evidence of malignancy. TB polymerase chain reaction and culture came positive for Mycobacterium tuberculosis. He was started on antituberculosis treatment with isoniazid, rifampicin, pyrazinamide, and ethambutol with a plan to continue for total 6 months. However, follow-up of the patient could not be done as he traveled back to his home country.

Investigation of genetic variation and lifestyle determinants in vitamin D levels in Arab individuals.

BACKGROUND: Differences in the concentrations of circulating 25-hydroxyvitamin D [25(OH)D] are associated with a wide range of health outcomes; however, most studies on genetic variants that impact 25(OH)D levels have been conducted in European populations. Here we aimed to identify common genetic variants that affect vitamin D concentrations in individuals of self-reported Arab ethnicity. METHODS: The study included 1151 Arab subjects living in Kuwait. Common variants of single-nucleotide polymorphisms and genes previously associated with vitamin D levels, such as GC, PDE3B, CYP2R1, and NADSYN1, were genotyped. Raw vitamin D level data were corrected for age, body mass index, and sex and then normalized. Regression tree analyses were performed to identify the impact of genetic variants on vitamin D levels. RESULTS: Compared with other gene variants, the GC gene variants exhibited the greatest impact on vitamin D levels in our study population, of which rs2298850 had the lowest p value (0.003). Individuals homozygous for the derived allele C had lower vitamin D levels. Analyses of the interaction between the number of years for which the subjects had lived in Kuwait and genetic variation in the GC gene showed that those with the CC genotype of rs2298850 who had lived in Kuwait for < 51 years had a mean 25(OH)D level of 10 ng/ml, whereas those who were homozygous for the ancestral allele had a mean 25(OH)D level of 17 ng/ml. Furthermore, subjects who had lived in Kuwait for > 51 years had higher vitamin D levels (mean 28 ng/ml) regardless of the genotype of their GC gene. CONCLUSIONS: The GC gene may play a major role in determining vitamin D levels in Arab populations.

Vitamin D insufficiency in Arabs and South Asians positively associates with polymorphisms in GC and CYP2R1 genes.

BACKGROUND: A number of genetic studies have reported an association between vitamin D related genes such as group-specific component gene (GC), Cytochrome P450, family 2, subfamily R, polypeptide 1 (CYP2R1) and 7-dehydrocholesterol reductase/nicotinamide-adenine dinucleotide synthetase 1 (DHCR7/NADSYN1) and serum levels of the active form of Vitamin D, 25 (OH) D among African Americans, Caucasians, and Chinese. Little is known about how genetic variations associate with, or contribute to, 25(OH)D levels in Arabs populations. METHODS: Allele frequencies of 18 SNPs derived from CYP2R1, GC, and DHCR7/NADSYN1 genes in 1549 individuals (Arabs, South Asians, and Southeast Asians living in Kuwait) were determined using real time genotyping assays. Serum levels of 25(OH)D were measured using chemiluminescence immunoassay. RESULTS: GC gene polymorphisms (rs17467825, rs3755967, rs2282679, rs7041 and rs2298850) were found to be associated with 25(OH)D serum levels in Arabs and South Asians. Two of the CYP2R1 SNPs (rs10500804 and rs12794714) and one of GC SNPs (rs1155563) were found to be significantly associated with 25(OH)D serum levels only in people of Arab origin. Across all three ethnicities none of the SNPs of DHCR7/NADSYN1 were associated with serum 25(OH)D levels and none of the 18 SNPs were significantly associated with serum 25(OH)D levels in people from South East Asia. CONCLUSION: Our data show for the first time significant association between the GC (rs2282679 and rs7041), CYP2R1 (rs10741657) SNPs and 25(OH)D levels. This supports their roles in vitamin D Insufficiency in Arab and South Asian populations respectively. Interestingly, two of the CYP2R1 SNPs (rs10500804 and rs12794714) and one GC SNP (rs1155563) were found to correlate with vitamin D in Arab population exclusively signifying their importance in this population.

Comparative evaluation of INNO-LiPA HBV assay, direct DNA sequencing and subtractive PCR-RFLP for genotyping of clinical HBV isolates.

Genotypes (A to H) of hepatitis B virus (HBV) influence liver disease progression and response to antiviral therapy in HBV-infected patients. Several methods have been developed for rapid genotyping of HBV strains. However, some of these methods may not be suitable for developing countries. The performance of INNO-LiPA HBV Genotyping assay (LiPA), direct DNA sequencing and subtractive PCR-RFLP of genotype-specific HBV genome regions were evaluated for accurately determining the HBV genotypes by analyzing sera (n = 80) samples from chronic HBV patients. Both, LiPA and DNA sequencing identified 63, 4 and 13 HBV strains as belonging to genotype D, genotype A and mixed genotype A and D, respectively. On the contrary, the PCR-RFLP-based method correctly identified all 4 genotype A but only 56 of 63 genotype D strains. Seven genotype D strains yielded indeterminate results. DNA sequence comparisons showed that a single nucleotide change in the target region generated an additional restriction site for Nla IV that compromised the accuracy of this method. Furthermore, all the mixed genotype A and D strains were identified only as genotype A strains. The data show that the PCR-RFLP-based method incorrectly identified some genotype D strains and failed to identify mixed genotype infections while LiPA and DNA sequencing yielded accurate results.

Construction of a modified vector for efficient purification of recombinant Mycobacterium tuberculosis proteins expressed in Escherichia coli.

A major problem in assessing the vaccine and diagnostic potential of various proteins encoded by Mycobacterium tuberculosis genome is the inability to produce large quantities of these proteins, even when Escherichia coli or other heterologous systems are employed for recombinant protein production. To overcome these barriers, we have constructed a modified expression vector, using pGEX-4T-1 vector as the backbone. In addition to the features offered by the pGEX-4T vectors, the new vector allowed easy purification of recombinant proteins on the highly versatile Ni-NTA-agarose affinity matrix. The utility of the new vector was demonstrated by expressing and purifying, to near homogeneity, two M. tuberculosis proteins, i.e., Rv3872 (a member of the multi-gene PE subfamily) and Rv3873 (a member of the multi-gene PPE subfamily), which are encoded by the RD1 region of M. tuberculosis. The proteins encoded by rv3872 and rv3873 were expressed at high levels as fusion proteins with glutathione-S-transferase in E. coli. The recombinant Rv3872 and Rv3873 proteins were purified and isolated free of the fusion partner (GST) by affinity purification on glutathione-Sepharose and/or Ni-NTA-agarose affinity matrix and cleavage of the purified fusion proteins by thrombin protease. The recombinant Rv3872 protein was nearly homogeneous (more than 95% pure) while Rv3873 preparation was more than 90% pure. The recombinant Rv3872 and Rv3873 proteins were immunologically active and reacted with antibodies in sera from TB patients. Our results demonstrate the utility of the newly constructed expression vector with two affinity tags for efficient expression and purification of recombinant M. tuberculosis proteins expressed in E. coli, which could be used for further diagnostic and immunological studies.