Genomic Epidemiology of Carbapenem-Resistant Klebsiella in Qatar: Emergence and Dissemination of Hypervirulent Klebsiella pneumoniae Sequence Type 383 Strains.

The emergence of carbapenem-resistant, hypervirulent Klebsiella pneumoniae is a new threat to health care. We studied the molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae isolates in Qatar using whole-genome sequence data. We also characterized the prevalence and genetic basis of hypervirulent phenotypes and established the virulence potential using a Galleria mellonella model. Of 100 Klebsiella isolates studied, NDM and OXA-48 were the most common carbapenemases. Core genome single-nucleotide polymorphism (SNP) analysis indicated the presence of diverse sequence types and clonal lineages; isolates belonging to Klebsiella quasipneumoniae subsp. quasipneumoniae sequence type 196 (ST196) and ST1416 may be disseminated among several health care centers. Ten K. pneumoniae isolates carried rmpA and/or truncated rmpA2, and 2 isolates belonged to KL2, indicating low prevalence of classical hypervirulent isolates. Isolates carrying both carbapenem resistance and hypervirulence genes were confined mainly to ST231 and ST383 isolates. One ST383 isolate was further investigated by MinION sequencing, and the assembled genome indicated that blaNDM was located on an IncHI1B-type plasmid (pFQ61_ST383_NDM-5) which coharbored several virulence factors, including the regulator of the mucoid phenotype (rmpA), the regulator of mucoid phenotype 2 (rmpA2), and aerobactin (iucABCD and iutA), likely resulting from recombination events. Comparative genomics indicated that this hybrid plasmid may be present in two additional Qatari ST383 isolates. Carbapenem-resistant, hypervirulent K. pneumoniae ST383 isolates pose an emerging threat to global health due to their simultaneous hypervirulence and multidrug resistance.

COVID-19 in adult acute myeloid leukemia patients: a long-term follow-up study from the European Hematology Association survey (EPICOVIDEHA).

Patients with acute myeloid leukemia (AML) are at high risk of dying from coronavirus disease 2019 (COVID-19). The optimal management of AML patients with COVID-19 has not been established. Our multicenter study included 388 adult AML patients diagnosed with COVID-19 between February 2020 and October 2021. The vast majority were receiving or had received AML treatment in the preceding 3 months. COVID-19 was severe in 41.2% and critical in 21.1% of cases. The chemotherapeutic schedule was modified in 174 patients (44.8%), delayed in 68 and permanently discontinued in 106. After a median follow-up of 325 days, 180 patients (46.4%) had died; death was attributed to COVID-19 (43.3%), AML (26.1%) or to a combination of both (26.7%), whereas in 3.9% of cases the reason was unknown. Active disease, older age, and treatment discontinuation were associated with death, whereas AML treatment delay was protective. Seventy-nine patients had a simultaneous AML and COVID-19 diagnosis, with better survival when AML treatment could be delayed (80%; P<0.001). Overall survival in patients with a diagnosis of COVID-19 between January 2020 and August 2020 was significantly lower than that in patients diagnosed between September 2020 and February 2021 and between March 2021 and September 2021 (39.8% vs. 60% vs. 61.9%, respectively; P=0.006). COVID-19 in AML patients was associated with a high mortality rate and modifications of therapeutic algorithms. The best approach to improve survival was to delay AML treatment, whenever possible.

Soluble ACE2 and angiotensin II levels are modulated in hypertensive COVID-19 patients treated with different antihypertension drugs.

PURPOSE: This study examines the effect of antihypertensive drugs on ACE2 and Angiotensin II levels in hypertensive COVID-19 patients. INTRODUCTION: Hypertension is a common comorbidity among severe COVID-19 patients. ACE2 expression can be modulated by antihypertensive drugs such as ACEis and ARBs, which may affect COVID-19's prognosis. BB and CCB reduce mortality, according to some evidence. Their effect on circulating levels of ACE2 and angiotensin II, as well as the severity of COVID-19, is less well studied. MATERIALS AND METHODS: The clinical data were collected from 200 patients in four different antihypertensive medication classes (ACEi, ARB, BB, and CCB). Angiotensin II and ACE2 levels were determined using standard ELISA kits. ACE2, angiotensin II, and other clinical indices were evaluated by linear regression models. RESULTS: Patients on ACEi (n = 57), ARB (n = 68), BB (n = 15), or CCB (n = 30) in this study had mild (n = 76), moderate (n = 76), or severe (n = 52) COVID-19. ACE2 levels were higher in COVID-19 patients with severe disease (p = 0.04) than mild (p = 0.07) and moderate (p = 0.007). The length of hospital stay is correlated with ACE2 levels (r = 0.3, p = 0.003). Angiotensin II levels decreased with severity (p = 0.04). Higher ACE2 levels are associated with higher CRP and D-dimer levels. Elevated Angiotensin II was associated with low levels of CRP, D-dimer, and troponin. ACE2 levels increase with disease severity in patients taking an ARB (p = 0.01), patients taking ACEi, the degree of disease severity was associated with a decrease in angiotensin II. BB patients had the lowest disease severity. CONCLUSION: We found different levels of soluble ACE2, and angiotensin II are observed among COVID-19 patients taking different antihypertensive medications and exhibiting varying levels of disease severity. COVID-19 severity increases with elevated ACE2 levels and lower angiotensin II levels indicating that BB treatment reduces severity regardless of levels of ACE2 and angiotensin II.

Remdesivir for patients with Coronavirus disease 2019 pneumonia requiring high oxygen support.

BACKGROUND: Treatment options for patients with critical Coronavirus Disease 2019 (COVID-19) are limited. This study aimed to describe the clinical characteristics and outcomes associated with remdesivir therapy in patients with COVID-19 who require non-invasive (NIV) ventilation or invasive mechanical ventilation (IMV). METHODS: Data were retrospectively extracted for adults with COVID-19 confirmed using polymerase chain reaction (PCR) between August 1, 2020 and January 28, 2021 who received ≥ 48 hours of remdesivir therapy while on NIV or IMV. Clinical improvement was defined as two-category improvement on an eight-point ordinal severity scale. RESULTS: A total of 133 individuals were included, of which 114 (85.7%) were on NIV and 19 (14.3%) were on IMV at the time of remdesivir initiation. The majority of the patients were males (62.4%), and the median age was 56 years. All the patients received concomitant dexamethasone therapy. Remdesivir treatment was commenced after a median of 7 days from onset of symptoms and was continued for a median of 5 days. Clinical improvement within 28 days was achieved in 101 patients (75.9%); among which, 78.1% and 63.2% were subjected to baseline NIV and IMV, respectively. Among the 11 (8.3%) patients who died of any cause by day 28, 9 (7.9%) and 2 (10.5%) were subjected to baseline NIV and IMV, respectively. The most frequent adverse events were sinus bradycardia (21, 13.1%) and alanine transaminase increase (18, 11.3%). Almost all adverse events were classified as Grades 1-3. CONCLUSION: The use of remdesivir in combination with systemic corticosteroids is associated with high recovery rates and low all-cause mortality in patients with COVID-19 pneumonia who require NIV or IMV. The results need confirmation from clinical trials of appropriate design and size.

Convalescent plasma for the treatment of patients with severe coronavirus disease 2019: A preliminary report.

BACKGROUND: The role of convalescent plasma therapy for patients with coronavirus disease 2019 (COVID-19) is unclear. METHODS: We retrospectively compared outcomes in a cohort of critical COVID-19 patients who received standard care (SC Group) and those who, in addition, received convalescent plasma (CP Group). RESULTS: In total, 40 patients were included in each group. The median patient age was 53.5 years (interquartile range [IQR] 42-60.5), and the majority of patients required invasive ventilation (69, 86.2%). Plasma was harvested from donors after a median of 37 days (IQR 31-46) from the first positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) result and 26 days (IQR 21-32) after documented viral clearance; it was administered after a median of 10 days (IQR 9-10) from the onset of symptoms and 2.5 days (IQR 2-4) from admission to intensive care unit. The primary endpoint of improvement in respiratory support status within 28 days was achieved in 26 patients (65%) in the SC Group and 31 patients (77.5%) in the CP Group (p = .32). The 28-day all-cause mortality (12.5% vs. 2.5%; p = .22) and viral clearance (65% vs. 55%; p = .49) were not significantly different between the two groups. Convalescent plasma was not significantly associated with the primary endpoint (adjusted hazard ratio 0.87; 95% confidence interval 0.51-1.49; p = .62). Adverse events were balanced between the two study groups. CONCLUSION: In severe COVID-19, convalescent plasma therapy was not associated with clinical benefits. Randomized trials are required to confirm our findings.

Diversity of carbapenem-resistant Klebsiella pneumoniae ST14 and emergence of a subgroup with KL64 capsular locus in the Arabian Peninsula.

To understand the reasons of successful spread of carbapenem-resistant Klebsiella pneumoniae ST14 (CRKP-ST14) in countries of the Arabian Peninsula, the resistome, capsular locus, carbapenemase carrying plasmid types, and core genome of isolates from the region were compared to global isolates. Thirty-nine CRKP-ST14 strains isolated from 13 hospitals in the United Arab Emirates, Bahrain, and Saudi Arabia were selected for whole genome sequencing on Illumina MiSeq platform based on the variety of carbapenemase genes carried and plasmids bearing these genes. Their resistome, capsular locus, and core genome MLST were compared to 173 CRKP-ST14 genomes available in public databases. The selected 39 CRKP-ST14 produced either NDM-1, OXA-48, OXA-162, OXA-232, KPC-2, or co-produced NDM-1 and an OXA-48-like carbapenemase. cgMLST revealed three clusters: 16 isolates from five UAE cities (C1), 11 isolates from three UAE cities and Bahrain (C2), and 5 isolates from Saudi Arabia (C3), respectively, and seven singletons. Resistance gene profile, carbapenemase genes, and their plasmid types were variable in both C1 and C2 clusters. The majority of CRKP-ST14 had KL2, but members of the C2 cluster and two further singletons possessed KL64 capsular locus. Based on cgMLST comparison of regional and global isolates, CRKP-ST14 with KL64 from four continents formed a distinct cluster, suggesting a recent emergence and spread of this variant. Our findings confirmed clonal transmission coupled with likely horizontal gene transfer in carbapenem-resistant Klebsiella pneumoniae ST14. Dissemination of this genetically flexible, highly resistant clone warrants further monitoring.

Molecular characterization of clinical carbapenem-resistant Enterobacterales from Qatar.

One hundred forty-nine carbapenem-resistant Enterobacterales from clinical samples obtained between April 2014 and November 2017 were subjected to whole genome sequencing and multi-locus sequence typing. Klebsiella pneumoniae (81, 54.4%) and Escherichia coli (38, 25.5%) were the most common species. Genes encoding metallo-ß-lactamases were detected in 68 (45.8%) isolates, and OXA-48-like enzymes in 60 (40.3%). blaNDM-1 (45; 30.2%) and blaOXA-48 (29; 19.5%) were the most frequent. KPC-encoding genes were identified in 5 (3.6%) isolates. Most common sequence types were E. coli ST410 (8; 21.1%) and ST38 (7; 18.4%), and K. pneumoniae ST147 (13; 16%) and ST231 (7; 8.6%).

Clinical characteristics and risk factors for COVID-19-associated Candidemia.

Patients with COVID-19-associated candidemia (CAC) in an intensive care unit (ICU) were matched 1:2 with those without candidemia, based on ICU admission date and length of stay in ICU being at least equal to that before candidemia in the corresponding case. The incidence rate of CAC was 2.34 per 1000 ICU days. Eighty cases could be matched to appropriate controls. In the multivariate conditional logistic regression analysis, age (P 0.001), and sequential organ failure assessment score (P 0.046) were the only risk factors independently associated with CAC. Tocilizumab and corticosteroids therapy were not independently associated with candidemia. LAY SUMMARY: In COVID-19 patients who need medical care in an intensive care unit, the risk of developing bloodstream Candida infection is higher in older patients and in those who have a more severe critical illness. Treatment with steroids or tocilizumab does not seem to affect the risk of candida bloodstream infection in these patients.

Coronavirus disease 2019 in solid organ transplant recipients in the setting of proactive screening and contact tracing of Qatar.

BACKGROUND: Clinical data on Coronavirus Disease 2019 (COVID-19) in solid organ transplant (SOT) recipients are limited. We herein report the initial clinical experience with COVID-19 in SOT recipients in Qatar. METHODS: All SOT recipients with laboratory-confirmed COVID-19 up to May 23, 2020 were included. Demographic and clinical data were extracted retrospectively from the hospital's electronic health records. Categorical data are presented as frequency and percentages, while continuous variables are summarized as medians and ranges. RESULTS: Twenty-four SOT recipients with COVID-19 were identified (kidney 16, liver 6, heart 1, and liver and kidney 1). Organ transplantation preceded COVID-19 by a median of 60 months (range 1.7-184). The median age was 57 years (range 24-72), and 9 (37.5%) transplant recipients were females. Five (21%) asymptomatic patients were diagnosed through proactive screening. For the rest, fever (15/19) and cough (13/19) were the most frequent presenting symptoms. Five (20.8%) patients required invasive mechanical ventilation in the intensive care unit (ICU). Eleven (46%) patients developed acute kidney injury, including three in association with drug-drug interactions involving investigational COVID-19 therapies. Maintenance immunosuppressive therapy was modified in 18 (75%) patients, but systemic corticosteroids were not discontinued in any. After a median follow-up of 226 days (26-272), 20 (83.3%) patients had been discharged home, 2 (8.3%) were still hospitalized, 1 (4.2%) was still in the ICU, and 1 (4.2%) had died. CONCLUSIONS: Our results suggest that asymptomatic COVID-19 is possible in SOT recipients and that overall outcomes are not uniformly worse than those in the general population. The results require confirmation in large, international cohorts.

Tocilizumab for the treatment of severe coronavirus disease 2019.

Tocilizumab, an interleukin-6 inhibitor, may ameliorate the inflammatory manifestations associated with severe coronavirus disease 2019 (COVID-19) and thus improve clinical outcomes. This was a retrospective review of patients with laboratory-confirmed severe COVID-19 who received tocilizumab and completed 14 days of follow up. Twenty-five patients were included, median age was 58 years (interquartile range, 50-63) and the majority were males (92%). Co-morbidities included diabetes mellitus (48%), chronic kidney disease (16%), and cardiovascular disease (12%). Fever (92%), cough (84%), and dyspnea (72%) were the commonest presenting symptoms. All patients received at least two concomitant investigational antiviral agents. Median oral temperature was on day 1, 3, and 7 was 38.0°C, 37.3°C (P = .043), and 37.0°C (P = .064), respectively. Corresponding median C-reactive protein was 193 and 7.9 mg/L (P < .0001) and <6 mg/L (P = .0001). Radiological improvement was noted in 44% of patients by day 7% and 68% by day 14. Nine patients (36%) were discharged alive from intensive care unit and three (12%) died. The proportion of patients on invasive ventilation declined from (84%) at the time of tocilizumab initiation to 60% on day 7 (P = .031) and 28% on day 14 (P = .001). The majority (92%) of patients experienced at least one adverse event. However, it is not possible to ascertain which adverse events were directly related to tocilizumab therapy. In patients with severe COVID-19, tocilizumab was associated with dramatic decline in inflammatory markers, radiological improvement and reduced ventilatory support requirements. Given the study's limitations, the results require assessment in adequately powered randomized controlled trials.

The first consecutive 5000 patients with Coronavirus Disease 2019 from Qatar; a nation-wide cohort study.

BACKGROUND: There are limited data on Coronavirus Disease 2019 (COVID-19) outcomes at a national level, and none after 60 days of follow up. The aim of this study was to describe national, 60-day all-cause mortality associated with COVID-19, and to identify risk factors associated with admission to an intensive care unit (ICU). METHODS: This was a retrospective cohort study including the first consecutive 5000 patients with COVID-19 in Qatar who completed 60 days of follow up by June 17, 2020. The primary outcome was all-cause mortality at 60 days after COVID-19 diagnosis. In addition, we explored risk factors for admission to ICU. RESULTS: Included patients were diagnosed with COVID-19 between February 28 and April 17, 2020. The majority (4436, 88.7%) were males and the median age was 35 years [interquartile range (IQR) 28-43]. By 60 days after COVID-19 diagnosis, 14 patients (0.28%) had died, 10 (0.2%) were still in hospital, and two (0.04%) were still in ICU. Fatal COVID-19 cases had a median age of 59.5 years (IQR 55.8-68), and were mostly males (13, 92.9%). All included pregnant women (26, 0.5%), children (131, 2.6%), and healthcare workers (135, 2.7%) were alive and not hospitalized at the end of follow up. A total of 1424 patients (28.5%) required hospitalization, out of which 108 (7.6%) were admitted to ICU. Most frequent co-morbidities in hospitalized adults were diabetes (23.2%), and hypertension (20.7%). Multivariable logistic regression showed that older age [adjusted odds ratio (aOR) 1.041, 95% confidence interval (CI) 1.022-1.061 per year increase; P < 0.001], male sex (aOR 4.375, 95% CI 1.964-9.744; P < 0.001), diabetes (aOR 1.698, 95% CI 1.050-2.746; P 0.031), chronic kidney disease (aOR 3.590, 95% CI 1.596-8.079, P 0.002), and higher BMI (aOR 1.067, 95% CI 1.027-1.108 per unit increase; P 0.001), were all independently associated with increased risk of ICU admission. CONCLUSIONS: In a relatively younger national cohort with a low co-morbidity burden, COVID-19 was associated with low all-cause mortality. Independent risk factors for ICU admission included older age, male sex, higher BMI, and co-existing diabetes or chronic kidney disease.

Clinical characteristics, microbiology, and outcomes of infective endocarditis in Qatar.

BACKGROUND: Infective endocarditis (IE) is a serious and potentially life-threatening disease. The epidemiology, treatment options, and outcomes have changed considerably over the last two decades. The aim of the study was to describe the epidemiology, clinical characteristics, and outcomes of patients with IE in Qatar. METHODS: Patients were identified from Hamad Medical Corporation hospitals' electronic records, the national referral center for the State of Qatar. We included those aged ≥ 18 years with Duke Criteria-based diagnosis of IE during the period from January 2015 to September 2017. Demographic and clinical data were retrieved. Descriptive statistics were performed, and logistic regression analysis was used to describe the relationship between patient characteristics and all-cause in-hospital mortality. All potentially relevant variables were included in the univariate analysis, while those with p < 0.1 in the univariate logistic regression model were included in the multivariate analysis. For the final model, we calculated odds ratios (OR) adjusted for each of the variables included, along with their 95% confidence intervals (95% CI). Data were analyzed using STATA software version 15 (StataCorp, College Station, Texas, USA). The study was approved by the Institutional Research Board with a waiver for informed consent. RESULTS: Fifty-seven cases were included, of which 70% were males. The mean age was 51 years ( ± 16.8 years). Eleven (19%) were associated with prosthetic valves, and 6 (11%) with implantable cardiac devices. Fever (84%), dyspnea (46%), and heart failure (37%) were the most common presentations. Only 58% of patients had known preexisting valvular heart disease or an intracardiac device. Skin infections (10 patients, 18%) were the most prevalent portals of infection, followed by venous catheters, recent valve surgery, and implantable cardiac devices. Staphylococci were implicated in 19 (34%) and Streptococcaceae in 9 (16%) patients, whereas 21 (37%) patients were culture negative. Left-side IE (49 patients, 86%) was predominant. Acute kidney injury (AKI) (17 patients, 30%) and heart failure (11 patients, 19%) were common complications. The majority of patients received targeted antimicrobial therapy with at least two active agents. Only 9 (16%) patients underwent surgical intervention. Fourteen (25%) patients died of any cause before hospital discharge. Logistic regression analysis identified septic shock [OR 57.8, 95% CI 2.6-1360.2; p < 0.01] and AKI OR 33.9, 95% CI 2.9-398.1; p < 0.01) as the only risk factors independently associated with in-hospital mortality. CONCLUSION: Staphylococci are the most common microbiological cause of IE in Qatar. Surgical intervention is uncommon, and mortality is relatively high. Our findings suggest that efforts should be directed toward improving IE prevention strategies in high-risk patients, encouraging early microbiological investigations and improving medical and surgical management.

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.

Clinical outcomes of current medical approaches for Middle East respiratory syndrome: A systematic review and meta-analysis.

Middle East respiratory syndrome (MERS) is a respiratory disease caused by MERS coronavirus. Because of lack of vaccination, various studies investigated the therapeutic efficacy of antiviral drugs and supportive remedies. A systematic literature search from 10 databases was conducted and screened for relevant articles. Studies reporting information about the treatment of MERS coronavirus infection were extracted and analyzed. Despite receiving treatment with ribavirin plus IFN, the case fatality rate was as high as 71% in the IFN-treatment group and exactly the same in patients who received supportive treatment only. Having chronic renal disease, diabetes mellitus and hypertension increased the risk of mortality (P < .05), and chronic renal disease is the best parameter to predict the mortality. The mean of survival days from onset of illness to death was 46.6 (95% CI, 30.5-62.6) for the IFN group compared with 18.8 (95% CI, 10.3-27.4) for the supportive-only group (P = .001). Delay in starting treatment, older age group, and preexisting comorbidities are associated with worse outcomes. In conclusion, there is no difference between IFN treatment and supportive treatment for MERS patients in terms of mortality. However, ribavirin and IFN combination might have efficacious effects with timely administration and monitoring of adverse events. Large-scale prospective randomized studies are required to assess the role of antiviral drugs for the treatment of this high mortality infection.

Aspergillus flavus native valve endocarditis following combined liver and renal transplantation: Case report and review of the literature.

Aspergillus endocarditis is a rare infection that occurs most commonly in patients with prior cardiac surgery but cases in post-transplant recipients without prior cardiac surgery have been reported. Diagnosis is often delayed and requires high index of suspicion. We here report a case of Aspergillus endocarditis in solid organ transplant recipient.

Presentation and outcome of Middle East respiratory syndrome in Saudi intensive care unit patients.

BACKGROUND: Middle East respiratory syndrome coronavirus infection is associated with high mortality rates but limited clinical data have been reported. We describe the clinical features and outcomes of patients admitted to an intensive care unit (ICU) with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. METHODS: Retrospective analysis of data from all adult (>18 years old) patients admitted to our 20-bed mixed ICU with Middle East respiratory syndrome coronavirus infection between October 1, 2012 and May 31, 2014. Diagnosis was confirmed in all patients using real-time reverse transcription polymerase chain reaction on respiratory samples. RESULTS: During the observation period, 31 patients were admitted with MERS-CoV infection (mean age 59 ± 20 years, 22 [71 %] males). Cough and tachypnea were reported in all patients; 22 (77.4 %) patients had bilateral pulmonary infiltrates. Invasive mechanical ventilation was applied in 27 (87.1 %) and vasopressor therapy in 25 (80.6 %) patients during the intensive care unit stay. Twenty-three (74.2 %) patients died in the ICU. Nonsurvivors were older, had greater APACHE II and SOFA scores on admission, and were more likely to have received invasive mechanical ventilation and vasopressor therapy. After adjustment for the severity of illness and the degree of organ dysfunction, the need for vasopressors was an independent risk factor for death in the ICU (odds ratio = 18.33, 95 % confidence interval: 1.11-302.1, P = 0.04). CONCLUSIONS: MERS-CoV infection requiring admission to the ICU is associated with high morbidity and mortality. The need for vasopressor therapy is the main risk factor for death in these patients.

High dose intravenous colistin methanesulfonate therapy is associated with high rates of nephrotoxicity; a prospective cohort study from Saudi Arabia.

BACKGROUND: Nephrotoxicity is an important adverse effect of colistin methanesulfonate (CMS) therapy. No data exist on rates and risk factors for colistin-related nephrotoxicity in Saudi Arabia (SA). We conducted a prospective cohort study to identify rates and risk factors for CMS nephrotoxicity in our patient population. METHODS: We prospectively included adult patients who received ≥48 hours of intravenous CMS therapy. Pregnant patients and those on renal replacement were excluded. Patients received 9 million units (mU) loading dose followed by 3 mU 8 hourly. In renal impairment, CMS dosing was adjusted according to calculated creatinine clearance (CrCl). Nephrotoxicity was defined as per RIFLE criteria (Risk, Injury, Failure, Loss and End-stage renal disease). Statistical analysis was performed using SPSS version 20.0 (IBM, Armonk, New York, USA). The study was approved by the institution's Research Ethics Committee. RESULTS: A total of 67 patients were included in the study. Mean (±standard deviation) age was 57.5 (±24.0) years, Charlson Co-morbidity Score 2.88 (±2.39), CrCl 133.60 (±92.54) mL/min and serum albumin 28.65 (±4.45) g/L. Mean CMS dose was 0.11 (±0.04) mU/kg/day and mean total CMS dose received was 101.21 (±47.37) mU. Fifty-one (76.1%) patients developed RIFLE-defined nephrotoxicity. Mean total CMS dose and duration of therapy before onset of nephrotoxicity were 66.71 (±43.45) mU and 8.70 (±6.70) days, respectively. In bivariate analysis, patients with nephrotoxicity were significantly older (P 0.013) and had lower baseline serum albumin (P 0.008). Multivariate logistic regression identified serum albumin [odds ratio (OR) 0.72; 95% confidence interval (CI) 0.57-0.93; P 0.010] and intensive care admission (OR 16.38; 95% CI 1.37-195.55; P 0.027) as independent risk factors for CMS nephrotoxicity. CONCLUSIONS: High dose intravenous CMS therapy is associated with high rates of nephrotoxicity in SA. Independent risk factors for colistin nephrotoxicity were baseline hypoalbuminemia and intensive care admission.