Epidemiology, Clinical, and Microbiological Characteristics of Multidrug-Resistant Gram-Negative Bacteremia in Qatar.

Antimicrobial resistance is a global healthcare threat with significant clinical and economic consequences peaking at secondary and tertiary care hospitals where multidrug-resistant Gram-negative bacteria (MDR GNB) lead to poor outcomes. A prospective study was conducted between January and December 2019 for all invasive bloodstream infections (BSIs) secondary to MDR GNB in Qatar identified during routine microbiological service to examine their clinical, microbiological, and genomic characteristics. Out of 3238 episodes of GNB BSIs, the prevalence of MDR GNB was 13% (429/3238). The predominant MDR pathogens were Escherichia coli (62.7%), Klebsiella pneumoniae (20.4%), Salmonella species (6.6%), and Pseudomonas aeruginosa (5.3%), while out of 245 clinically evaluated patients, the majority were adult males, with the elderly constituting almost one-third of the cohort and with highest observed risk for prolonged hospital stays. The risk factors identified included multiple comorbidities, recent healthcare contact, previous antimicrobial therapy, and admission to critical care. The in-hospital mortality rate was recorded at 25.7%, associated with multiple comorbidities, admission to critical care, and the acquisition of MDR Pseudomonas aeruginosa. Resistant pathogens demonstrated high levels of antimicrobial resistance but noticeable susceptibility to amikacin and carbapenems. Genomic analysis revealed that Escherichia coli ST131 and Salmonella enterica ST1 were the predominant clones not observed with other pathogens.

Antimicrobial Resistance in Qatar: Prevalence and Trends before and Amidst the COVID-19 Pandemic.

Antimicrobial resistance (AMR) is a global healthcare challenge with substantial morbidity, mortality, and management costs. During the COVID-19 pandemic, there was a documented increase in antimicrobial consumption, particularly for severe and critical cases, as well as noticeable travel and social restriction measures that might influenced the spectrum of AMR. To evaluate the problem, retrospective data were collected on bacterial infections and antimicrobial susceptibility patterns in Qatar before and after the pandemic from 1 January 2019 to 31 December 2021, covering 53,183 pathogens isolated from reported infection episodes. The findings revealed a significant resistance pattern for extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-EBC), carbapenem-resistant Enterobacteriaceae (CR-EBC), and carbapenem-resistant Pseudomonas aeruginosa (CRPA), ciprofloxacin-resistant Salmonella and methicillin-resistant Staphylococcus aureus (MRSA). For correlation with social restrictions, ESBL-EBC and MRSA were positively correlated with changing patterns of international travel (ρ = 0.71 and 0.67, respectively; p < 0.05), while CRPA was moderately correlated with the number of COVID-19 hospitalized patients (ρ = 0.49; p < 0.05). CREBC and CRPA respiratory infections were associated with hospitalized patients (OR: 3.08 and 2.00, respectively; p < 0.05). The findings emphasize the challenges experienced during the COVID-19 pandemic and links to international travel, which probably will influence the local epidemiology of AMR that needs further surveillance and control strategies.

Evaluation of Hospital Antimicrobial Stewardship Programs: Implementation, Process, Impact, and Outcomes, Review of Systematic Reviews.

Antimicrobial Stewardship Programs (ASP) were introduced in healthcare as a public health priority to promote appropriate prescribing of antimicrobials, to reduce adverse events related to antimicrobials, as well as to control the escalating challenges of antimicrobial resistance. To deliver aimed outcome objectives, ASPs involve multiple connected implementation process measures. A systematic review was conducted to evaluate both concepts of ASPs. Guided by PRISMA frames, published systematic reviews (SR) focusing on ASPs restricted to secondary and tertiary healthcare were evaluated over the past 10 years involving all age groups. Out of 265 identified SR studies, 63 met the inclusion criteria. The majority were conducted in Europe and North America, with limited studies from other regions. In the reviewed studies, all age groups were examined, although they were conducted mainly on adults when compared to children and infants. Both process and outcomes measures of ASPs were examined equally and simultaneously through 25 different concepts, dominated by efficacy, antimicrobial resistance, and economic impact, while information technology as well as role of pharmacy and behavioral factors were equally examined. The main broad conclusions from the review were that, across the globe, ASPs demonstrated effectiveness, proved efficacy, and confirmed efficiency, while focused evaluation advocated that developed countries should target medium- and small-sized hospitals while developing countries should continue rolling ASPs across healthcare facilities. Additionally, the future of ASPs should focus on embracing evolving information technology to bridge the gaps in knowledge, skills, and attitude, as well as to enhance appropriate decision making.

Phenotypic and Genotypic Characterization of Pan-Drug-Resistant Klebsiella pneumoniae Isolated in Qatar.

In secondary healthcare, carbapenem-resistant Enterobacterales (CREs), such as those observed in Klebsiella pneumoniae, are a global public health priority with significant clinical outcomes. In this study, we described the clinical, phenotypic, and genotypic characteristics of three pan-drug-resistant (PDR) isolates that demonstrated extended resistance to conventional and novel antimicrobials. All patients had risk factors for the acquisition of multidrug-resistant organisms, while microbiological susceptibility testing showed resistance to all conventional antimicrobials. Advanced susceptibility testing demonstrated resistance to broad agents, such as ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam. Nevertheless, all isolates were susceptible to cefiderocol, suggested as one of the novel antimicrobials that demonstrated potent in vitro activity against resistant Gram-negative bacteria, including CREs, pointing toward its potential therapeutic role for PDR pathogens. Expanded genomic studies revealed multiple antimicrobial-resistant genes (ARGs), including blaNMD-5 and blaOXA derivative types, as well as a mutated outer membrane porin protein (OmpK37).

The epidemiology and microbiological characteristics of infections caused by Gram-negative bacteria in Qatar: national surveillance from the Study for Monitoring of Antimicrobial Resistance Trends (SMART): 2017 to 2019.

Background: The global Study of Monitoring Antimicrobial Resistance Trends (SMART) is a surveillance program for evaluation of antimicrobial resistance (AMR) in Gram-negative bacteria (GNB) from different regions including Gulf countries. Objectives: To evaluate AMR in GNB from various clinical specimens including microbiological and genetic characteristics for existing and novel antimicrobials. Methods: A prospective study was conducted on clinical specimens from Hamad Medical Corporation, Qatar, between 2017 and 2019 according to the SMART protocol. Consecutive GNB from different sites were evaluated including lower respiratory, urinary tract, intrabdominal and bloodstream infections. Results: Over the 3 years study period, 748 isolates were evaluated from the specified sites comprising 37 different GNB outlining four key pathogens: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Stenotrophomonas maltophilia.For the two major pathogens E. coli and K. pneumoniae, phenotypic ESBL was identified in 55.77% (116/208) compared to 39% (73/187), while meropenem resistance was 3.8% compared to 12.8% and imipenem/relebactam resistance was 2.97% compared to 11.76%, respectively. The overall ceftolozane/tazobactam resistance for E. coli was 9.6% (20/208) compared to 14.97% (28/187) for K. pneumoniae while resistance for ceftazidime/avibactam was 3.65% (5/137) and 5.98% (10/117), respectively. Genomic characteristics of 70 Enterobacterales including 48 carbapenem-resistant, revealed prevalence of ß-lactamases from all classes, predominated by blaCXM-15 while carbapenem resistance revealed paucity of blaKPC and dominance of blaOXA-48 and blaNDM resistance genes. Conclusions: Surveillance of GNB from Qatar showed prevalence of key pathogens similar to other regions but demonstrated significant resistance patterns to existing and novel antimicrobials with different underlying resistance mechanisms.

Catastrophic complications of PVL-MRSA necrotizing pneumonia presenting as respiratory failure and rhabdomyolysis, case report and review of the literature.

Panton-Valentine leucocidin toxin-producing methicillin-resistant staphylococcus aureus is an important uncommon cause of community-acquired pneumonia; we describe a case of necrotizing pneumonia presenting as respiratory failure necessitating early initiation of extracorporeal membrane oxygenation, acute kidney injury and rhabdomyolysis, awareness, prompt recognition and appropriate management are crucial due to possible significant pathology.

Prevalence and microbiological and genetic characteristics of multidrug-resistant Pseudomonas aeruginosa over three years in Qatar.

Objectives: Antimicrobial resistance (AMR) is a global priority with significant clinical and economic consequences. Multidrug-resistant (MDR) Pseudomonas aeruginosa is one of the major pathogens associated with significant morbidity and mortality. In healthcare settings, the evaluation of prevalence, microbiological characteristics, as well as mechanisms of resistance is of paramount importance to overcome associated challenges. Methods: Consecutive clinical specimens of P. aeruginosa were collected prospectively from 5 acute-care and specialized hospitals between October 2014 and September 2017, including microbiological, clinical characteristics and outcomes. Identification and antimicrobial susceptibility test were performed using the BD Phoenix identification and susceptibility testing system, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS), and minimum inhibitory concentration (MIC) test strips. Overall, 78 selected MDR P. aeruginosa isolates were processed for whole-genome sequencing (WGS). Results: The overall prevalence of MDR P. aeruginosa isolates was 5.9% (525 of 8,892) and showed a decreasing trend; 95% of cases were hospital acquired and 44.8% were from respiratory samples. MDR P. aeruginosa demonstrated >86% resistance to cefepime, ciprofloxacin, meropenem, and piperacillin-tazobactam but 97.5% susceptibility to colistin. WGS revealed 29 different sequence types: 20.5% ST235, 10.3% ST357, 7.7% ST389, and 7.7% ST1284. ST233 was associated with bloodstream infections and increased 30-day mortality. All ST389 isolates were obtained from patients with cystic fibrosis. Encoded exotoxin genes were detected in 96.2% of isolates. Conclusions: MDR P. aeruginosa isolated from clinical specimens from Qatar has significant resistance to most agents, with a decreasing trend that should be explored further. Genomic analysis revealed the dominance of 5 main clonal clusters associated with mortality and bloodstream infections. Microbiological and genomic monitoring of MDR P. aeruginosa has enhanced our understanding of AMR in Qatar.

Evaluation of in Vitro Activity of Ceftazidime/Avibactam and Ceftolozane/Tazobactam against ESBL-producing Enterobacterales Isolated from Intensive Care Units from Qatar.

Objectives: Extended-spectrum -lactamases (ESBLs) mechanism of resistance in Enterobacterales leads to poor clinical outcomes. Ceftazidime/avibactam and ceftolozane/tazobactam are two broad-spectrum antimicrobial combinations that are effective against multidrug-resistant organisms with regional variations. This study aims to evaluate the antimicrobial susceptibility test (AST) for both combinations against ESBL-producing Enterobacterales isolated from intensive care units (ICUs) in tertiary hospitals from November 2012 to October 2013 in Qatar. Methods: A total of 629 Enterobacterales isolates from ICUs were screened for ESBL production using BD-PhoenixTM confirmed by double-disk potentiation, while ESBL-genes were detected by polymerase chain reaction. The ASTs for ceftazidime/avibactam and ceftolozane/tazobactam were assessed by minimum inhibitory concentration (MIC) test strips. A single isolate that was resistant to both combinations was subjected to whole-genome sequencing. Results: The prevalence of ESBL-producing Enterobacterales isolated from ICUs was 17.3% (109/629) with predominance of Klebsiella pneumoniae (56/109; 51.4%) and Escherichia coli (38/109; 34.9%). The susceptibility of ceftazidime/avibactam and ceftolozane/tazobactam against ESBL-producers was 99.1% (108/109) and most (81/109; 74.3%) had MICs < 0.5 for both combinations. The predominant ESBL-gene was blaCTX-M (72/109; 66.1%). A single isolate that was resistant to both combinations harbored multiple ESBL resistant-genes including blaVEB-5 and blaVIM-2. Conclusions: ESBL-producing Enterobacterales isolated from ICUs were predominantly K. pneumoniae and E. coli, mainly harboring blaCTX-M gene. They were highly susceptible to ceftazidime/avibactam and ceftolozane/tazobactam suggesting potential alternatives to currently available therapeutic options.

Dilemma of Tocilizumab therapy for a patient with critical COVID-19 disease and neutropenia: Case report and review of the literature.

Infection following SARS-Co V-2 leading to COVID-19 disease is associated with significant morbidity and mortality. The clinical entity, COVID-19 cytokine storm syndrome (CSS) is a severe immunological manifestation of the disease associated with ominous consequences. Tocilizumab is interleukin-6 inhibitors that has been shown to hamper the catastrophic outcomes of CCS including the need for mechanical ventilation as well as reduce mortality, but the usage is limited by warnings of reactivation of potential latent infections or immune dysfunctions including severe neutropenia. We describe a case of 39-year-old Nepalese male patient with a background of scleritis maintained on azathioprine and rituximab therapy with normal baseline parameters including complete blood count who presented with acute COVID-19 infection including associated leukopenia as well as severe neutropenia (absolute neutrophil count of 300 cells/µl), then progressed to critical disease culminating into CSS. Based on risks and benefits evaluation, the patient was treated with tocilizumab reinforced with granulocytes-colony stimulating factor (G-CSF, Filgrastim) to full recovery and safe outcome including reversal of neutropenia.

Remdesivir for COVID-19 pneumonia in patients with severe chronic kidney disease: A Case series and review of the literature.

Remdesivir was the first antiviral agent to receive FDA authorization for severe COVID-19 management, which restricts its use with severe renal impairment due to concerns that active metabolites might accumulate, causing renal toxicities. With limited treatment options, available evidence on such patient groups is important to assess for future safety.

Ominous combination: COVID-19 disease and Candida auris fungemia-Case report and review of the literature.

The identification of Candida auris fungemia in critically ill COVID-19 patients is detrimental, with huge implications on patient mortality and infectious control measures.

Schistosoma gallbladder polyp masquerading as a neoplasm: Rare case report and literature review.

Schistosomiasis affecting the gastrointestinal tract is common in tropical and subtropical areas but associated polyps presenting as gallbladder pathology are rare clinical entities necessitating high clinical suspicion.

The Spectrum of Antibiotic Prescribing During COVID-19 Pandemic: A Systematic Literature Review.

Objectives: Over the last decades, there has been a significant increase in antimicrobial prescribing and consumption associated with the development of patients' adverse events and antimicrobial resistance (AMR) to the point of becoming a global priority. This study aims at evaluating antibiotic prescribing during COVID-19 pandemic from November 2019 to December 2020. Materials and Methods: A systematic review was conducted primarily through the NCBI database, using PRISMA guidelines to identify relevant literature for the period between November 1, 2019 and December 19, 2020, using the keywords: COVID-19 OR SARS-Cov-2 AND antibiotics restricted to the English language excluding nonclinical articles. Five hundred twenty-seven titles were identified; all articles fulfilling the study criteria were included, 133 through the NCBI, and 8 through Google Scholar with a combined total of 141 studies. The patient's spectrum included all ages from neonates to elderly with all associated comorbidities, including immune suppression. Results: Of 28,093 patients included in the combined studies, 58.7% received antibiotics (16,490/28,093), ranging from 1.3% to 100% coverage. Antibiotics coverage was less in children (57%) than in adults with comorbidities (75%). Broad-spectrum antibiotics were prescribed presumptively without pathogen identifications, which might contribute to adverse outcomes. Conclusions: During the COVID-19 pandemic, there has been a significant and wide range of antibiotic prescribing in patients affected by the disease, particularly in adults with underlying comorbidities, despite the paucity of evidence of associated bacterial infections. The current practice might increase patients' immediate and long-term risks of adverse events, susceptibility to secondary infections as well as aggravating AMR.

Central line-associated Rhodotorula mucilaginosa fungemia in an immunocompetent host: Case report and review of the literature.

Rhodotorula mucilaginosa is an emerging fungal infection with the ability of biofilms formation. The identification of R mucilaginosa fungemia should trigger reflexes of prompt central venous line removal and using Amphotericin therapy.

Ancient foe spectra: Case series of Mycobacterium tuberculosis presentations.

Extrapulmonary tuberculosis frequently eludes assessment through atypical presentations and constitute diagnostic challenges. High degree of suspicion with aids of GeneXpert MTB/RIF can clinch the diagnosis and avoid unnecessary consequences.

Ancient foe, serious weapon: Subarachnoid hemorrhage secondary to TB meningitis.

Tuberculosis is an ancient infectious disease with global distribution and a multitude of multisystem presentations. Infection of the central nervous system (CNS) is the most serious presentation manifested as tuberculous meningitis (TBM), intracranial tuberculoma, and tuberculous arachnoiditis all associated with significant morbidity and mortality. TBM is the commonest form of CNS manifestations capable of causing secondary arteritis leading to vascular complications. We report a case of a 22-year-old Indian patient diagnosed with TBM who subsequently presented with sudden onset severe headache, which was eventually diagnosed as subarachnoid hemorrhage. Radiological assessment confirmed secondary complications with cerebral aneurysmal dilatation attributed to TBM. The patient was safely managed with combined radiological and surgical interventions with uneventful outcomes. Review of the literature revealed that such complication of TBM is rare usually with serious implications. We aim to highlight to infection specialists to be aware of such association.

Impact of an antimicrobial stewardship programme on antimicrobial utilization and the prevalence of MDR Pseudomonas aeruginosa in an acute care hospital in Qatar.

BACKGROUND: The excessive and inappropriate use of antibiotics is universal across all healthcare facilities. In Qatar there has been a substantial increase in antimicrobial consumption coupled with a significant rise in antimicrobial resistance (AMR). Antimicrobial stewardship programmes (ASPs) have become a standard intervention for effective optimization of antimicrobial prescribing. METHODS: A before-after study was conducted in Hamad General Hospital (603 bed acute care hospital): 1 year before implementation of a comprehensive ASP compared with the following 2 years. The ASP included a hospital-wide pre-authorization requirement by infectious diseases physicians for all broad-spectrum antibiotics. Prevalence of MDR Pseudomonas aeruginosa was compared with antimicrobial consumption, calculated as DDD per 1000 patient-days (DDD/1000 PD). Susceptibility was determined using broth microdilution, as per CLSI guidelines. Antibiotic use was restricted through the ASP, as defined in the hospital's antibiotic policy. RESULTS: A total of 6501 clinical isolates of P. aeruginosa were collected prospectively over 3 years (2014-17). Susceptibility to certain antimicrobials improved after the ASP was implemented in August 2015. The prevalence of MDR P. aeruginosa showed a sustained decrease from 2014 (9%) to 2017 (5.46%) (P = 0.019). There was a significant 23.9% reduction in studied antimicrobial consumption following ASP implementation (P = 0.008). The yearly consumption of meropenem significantly decreased from 47.32 to 31.90 DDD/1000 PD (P = 0.012), piperacillin/tazobactam from 45.35 to 32.67 DDD/1000 PD (P < 0.001) and ciprofloxacin from 9.71 to 5.63 DDD/1000 PD (P = 0.015) (from 2014 to 2017). CONCLUSIONS: The successful implementation of the ASP led to a significant reduction in rates of MDR P. aeruginosa, pointing towards the efficacy of the ASP in reducing AMR.

Evaluation of in vitro activity of ceftazidime/avibactam and ceftolozane/tazobactam against MDR Pseudomonas aeruginosa isolates from Qatar.

OBJECTIVES: To investigate the in vitro activity of ceftazidime/avibactam and ceftolozane/tazobactam against clinical isolates of MDR Pseudomonas aeruginosa from Qatar, as well as the mechanisms of resistance. METHODS: MDR P. aeruginosa isolated between October 2014 and September 2015 from all public hospitals in Qatar were included. The BD PhoenixTM system was used for identification and initial antimicrobial susceptibility testing, while Liofilchem MIC Test Strips (Liofilchem, Roseto degli Abruzzi, Italy) were used for confirmation of ceftazidime/avibactam and ceftolozane/tazobactam susceptibility. Ten ceftazidime/avibactam- and/or ceftolozane/tazobactam-resistant isolates were randomly selected for WGS. RESULTS: A total of 205 MDR P. aeruginosa isolates were included. Of these, 141 (68.8%) were susceptible to ceftazidime/avibactam, 129 (62.9%) were susceptible to ceftolozane/tazobactam, 121 (59.0%) were susceptible to both and 56 (27.3%) were susceptible to neither. Twenty (9.8%) isolates were susceptible to ceftazidime/avibactam but not to ceftolozane/tazobactam and only 8 (3.9%) were susceptible to ceftolozane/tazobactam but not to ceftazidime/avibactam. Less than 50% of XDR isolates were susceptible to ceftazidime/avibactam or ceftolozane/tazobactam. The 10 sequenced isolates belonged to six different STs and all produced AmpC and OXA enzymes; 5 (50%) produced ESBL and 4 (40%) produced VIM enzymes. CONCLUSIONS: MDR P. aeruginosa susceptibility rates to ceftazidime/avibactam and ceftolozane/tazobactam were higher than those to all existing antipseudomonal agents, except colistin, but were less than 50% in extremely resistant isolates. Non-susceptibility to ceftazidime/avibactam and ceftolozane/tazobactam was largely due to the production of ESBL and VIM enzymes. Ceftazidime/avibactam and ceftolozane/tazobactam are possible options for some patients with MDR P. aeruginosa in Qatar.