Survival implications vs. complications: unraveling the impact of vitamin D adjunctive use in critically ill patients with COVID-19-A multicenter cohort study.

Background: Despite insufficient evidence, vitamin D has been used as adjunctive therapy in critically ill patients with COVID-19. This study evaluates the effectiveness and safety of vitamin D as an adjunctive therapy in critically ill COVID-19 patients. Methods: A multicenter retrospective cohort study that included all adult COVID-19 patients admitted to the intensive care units (ICUs) between March 2020 and July 2021. Patients were categorized into two groups based on their vitamin D use throughout their ICU stay (control vs. vitamin D). The primary endpoint was in-hospital mortality. Secondary outcomes were the length of stay (LOS), mechanical ventilation (MV) duration, and ICU-acquired complications. Propensity score (PS) matching (1:1) was used based on the predefined criteria. Multivariable logistic, Cox proportional hazards, and negative binomial regression analyses were employed as appropriate. Results: A total of 1,435 patients were included in the study. Vitamin D was initiated in 177 patients (12.3%), whereas 1,258 patients did not receive it. A total of 288 patients were matched (1:1) using PS. The in-hospital mortality showed no difference between patients who received vitamin D and the control group (HR 1.22, 95% CI 0.87-1.71; p = 0.26). However, MV duration and ICU LOS were longer in the vitamin D group (beta coefficient 0.24 (95% CI 0.00-0.47), p = 0.05 and beta coefficient 0.16 (95% CI -0.01 to 0.33), p = 0.07, respectively). As an exploratory outcome, patients who received vitamin D were more likely to develop major bleeding than those who did not [OR 3.48 (95% CI 1.10, 10.94), p = 0.03]. Conclusion: The use of vitamin D as adjunctive therapy in COVID-19 critically ill patients was not associated with survival benefits but was linked with longer MV duration, ICU LOS, and higher odds of major bleeding.

A Drug Repurposing Screen Identifies Fludarabine Phosphate as a Potential Therapeutic Agent for N-MYC Overexpressing Neuroendocrine Prostate Cancers.

Neuroendocrine prostate cancer (NEPC) represents a highly aggressive form of prostate tumors. NEPC results from trans-differentiated castration-resistant prostate cancer (CRPC) with increasing evidence indicating that the incidence of NEPC often results from the adaptive response to androgen deprivation therapy. Recent studies have shown that a subset of NEPC exhibits overexpression of the MYCN oncogene along with the loss of tumor suppressing TP53 and RB1 activities. N-MYC is structurally disordered with no binding pockets available on its surface and so far, no clinically approved drug is available. We adopted a drug-repurposing strategy, screened ~1800 drug molecules, and identified fludarabine phosphate to preferentially inhibit the proliferation of N-MYC overexpressing NEPC cells by inducing reactive oxygen species (ROS). We also show that fludarabine phosphate affects N-MYC protein levels and N-MYC transcriptional targets in NEPC cells. Moreover, enhanced ROS production destabilizes N-MYC protein by inhibiting AKT signaling and is responsible for the reduced survival of NEPC cells and tumors. Our results indicate that increasing ROS production by the administration of fludarabine phosphate may represent an effective treatment option for patients with N-MYC overexpressing NEPC tumors.

The association of timing of pharmacological prophylaxis and venous thromboembolism in patients with moderate-to-severe traumatic brain injury: A retrospective cohort study.

OBJECTIVES: Patients with traumatic brain injury (TBI) have an increased risk for venous thromboembolism (VTE). The current guidelines recommend pharmacologic prophylaxis, but its timing remains unclear. METHODS: In this retrospective cohort study, patients with moderate-to-severe TBI admitted to a tertiary care intensive care unit between 2016 and 2019 were categorized into two groups according to the timing of pharmacologic prophylaxis: early if prophylaxis was given within 72 h from hospital admission and late if after 72 h. RESULTS: Of the 322 patients in the cohort, 46 (14.3%) did not receive pharmacological prophylaxis, mainly due to early brain death; 152 (47.2%) received early pharmacologic prophylaxis and 124 (38.5%) received late prophylaxis. Predictors of late pharmacologic prophylaxis were lower body mass index, intracerebral hemorrhage (odds ratio [OR], 3.361; 95% confidence interval [CI], 1.269-8.904), hemorrhagic contusion (OR, 3.469; 95% CI, 1.039-11.576), and lower platelet count. VTE was diagnosed in 43 patients on a median of 10 days after trauma (Q1, Q3: 5, 15): 6.6% of the early prophylaxis group and 26.6% of the late group (P < 0.001). On multivariable logistic regression analysis, the predictors of VTE were Acute Physiology and Chronic Health Evaluation II score, subarachnoid hemorrhage, and late versus early pharmacologic prophylaxis (OR, 3.858; 95% CI, 1.687-8.825). The late prophylaxis group had higher rate of tracheostomy, longer duration of mechanical ventilation and stay in the hospital, lower discharge Glasgow coma scale, but similar survival, compared with the early group. CONCLUSIONS: Late prophylaxis (>72 h) was associated with higher VTE rate in patients with moderate-to-severe TBI, but not with higher mortality.

The Impact of Hyperoxia Treatment on Neurological Outcomes and Mortality in Moderate to Severe Traumatic Brain Injured Patients.

BACKGROUND: Traumatic brain injury is a leading cause of morbidity and mortality worldwide. The relationship between hyperoxia and outcomes in patients with TBI remains controversial. We assessed the effect of persistent hyperoxia on the neurological outcomes and survival of critically ill patients with moderate-severe TBI. METHOD: This was a retrospective cohort study of all adults with moderate-severe TBI admitted to the ICU between 1st January 2016 and 31st December 2019 and who required invasive mechanical ventilation. Arterial blood gas data was recorded within the first 3 hours of intubation and then after 6-12 hours and 24-48 hours. The patients were divided into two categories: Group I had a PaO2 < 120mmHg on at least two ABGs undertaken in the first twelve hours post intubation and Group II had a PaO2 ≥ 120mmHg on at least two ABGs in the same period. Multivariable logistic regression was performed to assess predictors of hospital mortality and good neurologic outcome (Glasgow outcome score ≥ 4). RESULTS: The study included 309 patients: 54.7% (n=169) in Group I and 45.3% (n=140) in Group II. Hyperoxia was not associated with increased mortality in the ICU (20.1% vs. 17.9%, p=0.62) or hospital (20.7% vs. 17.9%, p=0.53), moreover, the hospital discharge mean (SD) Glasgow Coma Scale (11.0(5.1) vs. 11.2(4.9), p=0.70) and mean (SD) Glasgow Outcome Score (3.1(1.3) vs. 3.1(1.2), p=0.47) were similar. In multivariable logistic regression analysis, persistent hyperoxia was not associated with increased mortality (adjusted odds ratio [aOR] 0.71, 95% CI 0.34-1.35, p=0.29). PaO2 within the first 3 hours was also not associated with mortality: 121-200mmHg: aOR 0.58, 95% CI 0.23-1.49, p=0.26; 201-300mmHg: aOR 0.66, 95% CI 0.27-1.59, p=0.35; 301-400mmHg: aOR 0.85, 95% CI 0.31-2.35, p=0.75 and >400mmHg: aOR 0.51, 95% CI 0.18-1.44, p=0.20; reference: PaO2 60-120mmHg within 3 hours. However, hyperoxia >400mmHg was associated with being less likely to have good neurological (GOS ≥4) outcome on hospital discharge (aOR 0.36, 95% CI 0.13-0.98, p=0.046; reference: PaO2 60-120mmHg within 3 hours. CONCLUSION: In intubated patients with moderate-severe TBI, hyperoxia in the first 48 hours was not independently associated with hospital mortality. However, PaO2 >400mmHg may be associated with a worse neurological outcome on hospital discharge.

The Effect of Personalized Patient Videos on Patient Satisfaction After Arthroscopic Shoulder Surgery.

Dissatisfaction after shoulder arthroscopy may be influenced by the information that patients receive. Multimedia is an emerging modality of information delivery. The goal of this study was to evaluate whether providing patients with a personalized video of their arthroscopic shoulder surgery improved satisfaction through a multisurgeon randomized controlled study. Patients undergoing arthroscopic shoulder decompression, rotator cuff repair, or labral repair were randomized to either the intervention group, receiving a video recording of their surgery, or the control group, not receiving a video. Patients who had previous ipsilateral shoulder arthroscopy or who could not participate in follow-up were excluded. Patient satisfaction was assessed at 3 months with a visual analog scale (VAS), Likert scale, and Quick Disabilities of the Arm, Hand and Shoulder (QuickDASH) score. The intervention group included 50 participants, and the control group included 47 participants, with 18% loss to follow-up. Mean control group VAS score was 8.5±2.2 and intervention group VAS score was 9.0±1.5, a difference that was not significantly different (P=.27). No statistically significant differences were noted for Likert scale scores and QuickDASH scores. A subgroup analysis of age group, sex, surgeon, and surgical procedure showed no significant differences. Based on these findings, personalized patient videos do not appear to improve satisfaction with surgery. Surgeons should investigate other means to improve patient satisfaction in the small group of dissatisfied patients. [Orthopedics. 2021;44(3):e331-e336.].

The Effects of Patient Resilience and Catastrophizing on Carpal Tunnel Surgical Outcomes.

Purpose: Outcomes following carpal tunnel release (CTR) are generally favorable. When patient satisfaction or symptom resolution is not as expected, understanding what factors contribute to that outcome could allow for strategies targeted at improving results. Our purpose was to determine if measurable mental health factors, specifically resilience and pain catastrophization, correlate with patients' postoperative outcomes following CTR. Methods: A prospective cohort study was performed. Ninety-four patients were recruited to take part in the study. Patients completed written consent, the Boston Carpal Tunnel Questionnaire (BCTQ), the Pain Catastrophizing Scale, and the Brief Resilience Scale. A single surgeon, or his resident under supervision, performed an open CTR under local anesthetic. Our primary outcome measure was a repeat BCTQ at 6 months. Pearson correlation coefficients and univariate analyses were performed to assess the correlation between Pain Catastrophizing Scale and Brief Resilience Scale scores and final BCTQ scores. Results: Forty-three and 63 participants completed the BCTQ at 3 and 6 months, respectively. This was 10% below the number needed to achieve appropriate power. Among those that responded, all participants showed improvement in their symptoms (P = .001). There was no correlation between patients' Pain Catastrophizing Scale or Brief Resilience Scale scores and 6-month BCTQ scores or the amount of improvement in the BCTQ at final follow-up. Conclusions: Most participants improved following CTR. Patients' self-assessed resilience, and the degree of pain catastrophization did no correlate with the amount of improvement patients had after surgery. Type of study/level of evidence: Prognostic II.

Invasive Candidiasis in Critically Ill Patients: A Prospective Cohort Study in Two Tertiary Care Centers.

BACKGROUND: Invasive candidiasis is not uncommon in critically ill patients but has variable epidemiology and outcomes between intensive care units (ICUs). This study evaluated the epidemiology, characteristics, management, and outcomes of patients with invasive candidiasis at 6 ICUs of 2 tertiary care centers. METHODS: This was a prospective observational study of all adults admitted to 6 ICUs in 2 different hospitals between August 2012 and May 2016 and diagnosed to have invasive candidiasis by 2 intensivists according to predefined criteria. The epidemiology of isolated Candida and the characteristics, management, and outcomes of affected patients were studied. Multivariable logistic regression analyses were performed to identify the predictors of non-albicans versus albicans infection and hospital mortality. RESULTS: Invasive candidiasis was diagnosed in 162 (age 58.4 ± 18.9 years, 52.2% males, 82.1% medical admissions, and admission Acute Physiology and Chronic Health Evaluation II score 24.1 ± 8.4) patients at a rate of 2.6 cases per 100 ICU admissions. On the diagnosis day, the Candida score was 2.4 ± 0.9 in invasive candidiasis compared with 1.6 ± 0.9 in Candida colonization (P < .01). The most frequent species were albicans (38.3%), tropicalis (16.7%), glabrata (16%), and parapsilosis (13.6%). In patients with candidemia, antifungal therapy was started on average 1 hour before knowing the culture result (59.6% of therapy initiated after). Resistance to fluconazole, caspofungin, and amphotericin B occurred in 27.9%, 2.9%, and 3.1%, respectively. The hospital mortality was 58.6% with no difference between albicans and non-albicans infections (61.3% and 54.9%, respectively; P = .44). The independent predictors of mortality were renal replacement therapy after invasive candidiasis diagnosis (odds ratio: 5.42; 95% confidence interval: 2.16-13.56) and invasive candidiasis leading/contributing to ICU admission versus occurring during critical illness (odds ratio: 2.87; 95% confidence interval: 1.22-6.74). CONCLUSIONS: In critically ill patients with invasive candidiasis, non-albicans was responsible for most cases, and mortality was high (58.6%). Antifungal therapy was initiated after culture results in 60% suggesting low preclinical suspicion. Study registration: NCT01490684; registered in ClinicalTrials.gov on February 11, 2012.

Dosing errors of empirical antibiotics in critically ill patients with severe sepsis or septic shock: A prospective observational study.

BACKGROUND: Effective antibiotic therapy is crucial in sepsis management. Studies have emphasized on antibiotic administration timing more than dosing. We evaluated the frequency and risk factors of antibiotic dosing errors in sepsis. MATERIALS AND METHODS: This prospective observational study compared the doses of intravenous empirical antibiotics in the 1st day of sepsis diagnosis with those recommended by Micromedex, considering sepsis source and glomerular filtration rate estimated by the modification of diet in renal disease equation. The doses were classified as under-dosed, over-dosed, or appropriate. We excluded antibiotics which did not need a dose adjustment. The under-dosing rate was retrospectively evaluated according to the creatinine clearance estimated by the Cockcroft-Gault equation. RESULTS: Between October 1, 2013, and April 30, 2014, 189 patients were evaluated (age 61.6 ± 18.6 years, acute physiology and chronic health evaluation II score 22.8 ± 7.0, 58.7% septic shock) with 415 antibiotic prescriptions (2.2 ± 0.9 prescriptions per patient). Antibiotic dosing was appropriate in 50.8% of patients; under-dosing in 30.7% and overdosing in 25.9%. Under-dosing prevalence was 39.4% when kidney function was assessed by the Cockcroft-Gault equation. Vancomycin was associated with the highest under-dosing rate (39.4%), followed by piperacillin/tazobactam (12.1%). The cohort mortality was 35.4%. Age, shock, chronic kidney disease, and cirrhosis independently predicted mortality on multivariable logistic regression analysis. Antibiotic dosing error was not associated with mortality: Over-versus appropriate dosing (odds ratio [OR], 1.41; 95% confidence interval [CI], 0.57-3.47), under-versus appropriate dosing (OR, 0.57; 95% CI, 0.24-1.35). CONCLUSIONS: Antibiotic dosing errors were common in patients with sepsis. Vancomycin had the highest under-dosing rate. Antibiotic dosing errors were not associated with increased mortality.

Implementing the comprehensive unit-based safety program model to improve the management of mechanically ventilated patients in Saudi Arabia.

BACKGROUND: Ventilator-associated events are common in mechanically ventilated patients. They are associated with more days on mechanical ventilation, longer intensive care unit (ICU) stay, and increased risk of mortality. Theoretically, interventions that prevent ventilator-associated events should also reduce associated morbidity. We evaluated the Comprehensive Unit-based Safety Program approach to improve the care of mechanically ventilated patients. METHODS: All mechanically ventilated patients admitted to the ICU between October 1, 2015, and October 31, 2016, were prospectively monitored for the development of ventilator-associated events according to the National Healthcare Safety Network criteria. A process care bundle (endotracheal intubation with subglottic suctioning, head-of-bed elevation ≥30°, target sedation scores, daily spontaneous awakening trials, spontaneous breathing trials), daily delirium assessment, and an early mobility protocol were instituted. The bundle compliance, ventilator-associated events rates, ICU length of stay, and mortality rate were noted. The database allowed viewing of current rates, trends, and averages of all participating sites. RESULTS: In the study period, 2,321 patients were admitted to the ICU, and 1,231 required mechanical ventilation (10,342 ventilator days). There were 115 ventilator-associated events: 82 ventilator-associated conditions, 15 infection-related ventilator-associated conditions, and 18 possible cases of ventilator-associated pneumonia. The ICU mortality rate was 13.3%, compared with 28.7% for those mechanically ventilated patients with ventilator-associated events (P = .0001). There was increased compliance for spontaneous awakening trials (51.5%-76.9%, P = .0008) and spontaneous breathing trials (54.2%-72.2%, P = .02) and a decrease in infection-related ventilator-associated conditions (4.2-3.5 per 1,000 days), possible cases of ventilator-associated pneumonia (2.1-1.7 per 1,000 days), ICU mortality (45.3%-19.1%, P = .045), and ventilator-associated events associated mortality rates (33.3%-8.3%, P < .37). Physical therapy participation and mobility were 60.8% and 26.4%, respectively. CONCLUSION: The implementation of a multipronged program like the Comprehensive Unit-based Safety Program could improve the care processes and outcomes of mechanically ventilated patients.

Introducing the Comprehensive Unit-based Safety Program for mechanically ventilated patients in Saudi Arabian Intensive Care Units.

Over the past decade, there have been major improvements to the care of mechanically ventilated patients (MVPs). Earlier initiatives used the concept of ventilator care bundles (sets of interventions), with a primary focus on reducing ventilator-associated pneumonia. However, recent evidence has led to a more comprehensive approach: The ABCDE bundle (Awakening and Breathing trial Coordination, Delirium management and Early mobilization). The approach of the Comprehensive Unit-based Safety Program (CUSP) was developed by patient safety researchers at the Johns Hopkins Hospital and is supported by the Agency for Healthcare Research and Quality to improve local safety cultures and to learn from defects by utilizing a validated structured framework. In August 2015, 17 Intensive Care Units (ICUs) (a total of 271 beds) in eight hospitals in the Kingdom of Saudi Arabia joined the CUSP for MVPs (CUSP 4 MVP) that was conducted in 235 ICUs in 169 US hospitals and led by the Johns Hopkins Armstrong Institute for Patient Safety and Quality. The CUSP 4 MVP project will set the stage for cooperation between multiple hospitals and thus strives to create a countrywide plan for the management of all MVPs in Saudi Arabia.

The critical care response to a hospital outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection: an observational study.

BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) has caused several hospital outbreaks, including a major outbreak at King Abdulaziz Medical City, a 940-bed tertiary-care hospital in Riyadh, Saudi Arabia (August-September 2015). To learn from our experience, we described the critical care response to the outbreak. METHODS: This observational study was conducted at the Intensive Care Department which covered 5 ICUs with 60 single-bedded rooms. We described qualitatively and, as applicable, quantitatively the response of intensive care services to the outbreak. The clinical course and outcomes of healthcare workers (HCWs) who had MERS were noted. RESULTS: Sixty-three MERS patients were admitted to 3 MERS-designated ICUs during the outbreak (peak census = 27 patients on August 25, 2015, and the last new case on September 13, 2015). Most patients had multiorgan failure. Eight HCWs had MERS requiring ICU admission (median stay = 28 days): Seven developed acute respiratory distress syndrome, four were treated with prone positioning, four needed continuous renal replacement therapy and one had extracorporeal membrane oxygenation. The hospital mortality of ICU MERS patients was 63.4 % (0 % for the HCWs). In response to the outbreak, the number of negative-pressure rooms was increased from 14 to 38 rooms in 3 MERS-designated ICUs. Patients were managed with a nurse-to-patient ratio of 1:0.8. Infection prevention practices were intensified. As a surrogate, surface disinfectant and hand hygiene gel consumption increased by ~30 % and 17 N95 masks were used per patient/day on average. Family visits were restricted to 2 h/day. Although most ICU staff expressed concerns about acquiring MERS, all reported to work normally. During the outbreak, 27.0 % of nurses and 18.4 % of physicians working in the MERS-designated ICUs reported upper respiratory symptoms, and were tested for MERS-CoV. Only 2/196 (1.0 %) ICU nurses and 1/80 (1.3 %) physician tested positive, had mild disease and recovered fully. The total sick leave duration was 138 days for nurses and 30 days for physicians. CONCLUSIONS: Our hospital outbreak of MERS resulted in 63 patients requiring organ support and prolonged ICU stay with a high mortality rate. The ICU response required careful facility and staff management and proper infection control and prevention practices.

Middle East respiratory syndrome coronavirus on inanimate surfaces: A risk for health care transmission.

The Middle East Respiratory syndrome coronavirus (MERS-CoV) has been responsible for multiple health care-associated outbreaks. We investigated whether high-touch surfaces in 3 rooms of laboratory-confirmed MERS-CoV patients were contaminated with MERS-CoV RNA. We found 2 out of 51 surfaces were contaminated with MERS-CoV viral genetic material. Hence, environmental contamination may be a potential source of health care transmission and outbreaks. Meticulous environmental cleaning may be important in preventing transmission within the health care setting.

Multifaceted bundle interventions shown effective in reducing VAP rates in our multidisciplinary ICUs.

Ventilator associated pneumonia (VAP) remains a worldwide harm associated with hospital acquired infection. Our VAP rate at King Abdulaziz Medical City was 4.0 per 1 000 patient days at baseline. All regulatory bodies continue to emphasize the importance of reducing these infections and include a guideline of practice recommendations to address them, notably the VAP bundle by the Institute for Healthcare Improvement. Our baseline compliance was low and measured to be 83%; this was perceived as an opportunity to work on revising our interventions in the ICUs. An improvement team gathered in 2013, and following the "model of improvement" methodology, along with a sequence of parallel PDSAs, they were able to increase compliance with the care bundle and sustain it above 95% for more than one year. This translated in a decrease in the VAP rate from 4.0 to 0.8 in all different multidisciplinary ICUs.

The impact of implementing multifaceted interventions on the prevention of ventilator-associated pneumonia.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a frequent hospital acquired infections among intensive care unit patients. The Institute for Healthcare Improvement has suggested a "care bundle" approach for the prevention of VAP. This report describes the effects of implementing this strategy on VAP rates. METHODS: All mechanically ventilated patients admitted to the intensive care unit between 2008 and 2013 were prospectively followed for VAP development according to the National Healthcare Safety Network criteria. In 2011, a 7-element care bundle was implemented, including head-of-bed elevation 30°-45°, daily sedation vacation and assessment for extubation, peptic ulcer disease prophylaxis, deep vein thrombosis prophylaxis, oral care with chlorhexidine, endotracheal intubation with in-line suction and subglottic suctioning, and maintenance of endotracheal tube cuff pressure at 20-30 mmHg. The bundle compliance and VAP rates were then followed. RESULTS: A total of 3665 patients received mechanical ventilation, and there were 9445 monitored observations for bundle compliance. The total bundle compliance before and after initiation of the VAP team was 90.7% and 94.2%, respectively (P < .001). The number of VAP episodes decreased from 144 during 2008-2010 to only 14 during 2011-2013 (P < .0001). The rate of VAP decreased from 8.6 per 1000 ventilator-days to 2.0 per 1000 ventilator-days (P < .0001) after implementation of the care bundle. CONCLUSIONS: This study suggests that systematic implementation of a multidisciplinary team approach can reduce the incidence of VAP. Further sustained improvement requires persistent vigilant inspections.

The impact of onset time on the isolated pathogens and outcomes in ventilator associated pneumonia.

Several guidelines base the empirical therapy of ventilator-associated pneumonia (VAP) on the time of onset. However, there is emerging evidence that the isolated microorganisms may be similar regardless of onset time. This study evaluated the characteristics and outcomes of VAP with different onset times. All of the mechanically ventilated patients admitted to the ICU of a 900-bed tertiary-care hospital between 01/08/2003 and 31/12/2010 were prospectively followed for VAP development according to the National Healthcare Safety Network criteria. The patients were categorized into four groups: EO if VAP occurred within 4 days of intubation and hospital admission; LO if VAP occurred after 4 days of admission; EL if VAP occurred within 4 days of intubation, but after the fourth hospitalization day; and LL if VAP occurred after the fourth day of intubation and hospitalization. Out of the 394 VAP episodes, 63 (16%) were EO episodes, 331 (84.0%) were LO episodes, 40 (10.1%) were EL episodes and 291 (73.1%) were LL episodes. The isolated microorganisms were comparable among the four groups, with a similar rate of potentially multidrug resistant organisms in the EO-VAP (31.7%), LO-VAP (40.8%), EL-VAP (37.5%) and LL-VAP (43.3%) samples. The hospital mortality was 24% for EO-VAP cases, 28% for LO-VAP cases, 40% for EL-VAP cases and 49% for LL-VAP cases. However, in the adjusted multivariate analysis, neither LO-VAP, EL-VAP nor LL-VAP was associated with an increased risk of hospital mortality compared with EO-VAP (OR, 0.86 95% CI, 0.34-2.19; 1.22; 95% CI, 0.41-3.68, and 0.95; 95% CI, 0.43-2.10, respectively). In this study, the occurrence of potential multidrug resistant pathogens and the mortality risk were similar regardless of VAP timing from hospital admission and intubation. The bacterial isolates obtained from the VAP cases did not follow an early vs. late-onset pattern, and thus, these terms may not be clinically helpful.

Drug-resistant ventilator associated pneumonia in a tertiary care hospital in Saudi Arabia.

BACKGROUND: There is a wide geographic and temporal variability of bacterial resistance among microbial causes of ventilator-associated pneumonia (VAP). The contribution of multi-drug resistant (MDR) pathogens to the VAP etiology in Saudi Arabia was never studied. We sought to examine the extent of multiple-drug resistance among common microbial causes of VAP. MATERIALS AND METHODS: We conducted a retrospective susceptibility study in the adult intensive care unit (ICU) of King Abdulaziz Medical City, Riyadh, Saudi Arabia. Susceptibility results of isolates from patients diagnosed with VAP between October 2004 and June 2009 were examined. The US National Healthcare Safety Network definition of MDR was adopted. RESULTS: A total of 248 isolates including 9 different pathogens were included. Acinetobacter spp. was highly (60-89%) resistant to all tested antimicrobials, including carbapenems (three- and four-class MDR prevalence were 86% and 69%, respectively). Pseudomonas aeruginosa was moderately (13-31%) resistant to all tested antimicrobials, including antipseudomonal penicillins (three- and four-class MDR prevalence were 13% and 10%, respectively). With an exception of ampicillin (fully resistant), Klebsiella spp. had low (0-13%) resistance to other tested antimicrobials with no detected MDR. Staphylococcus aureus was fully susceptible to vancomycin with 42% resistance to oxacillin. There were significant increasing trends of MDR Acinetobacter spp. however not P. aeruginosa during the study. Resistant pathogens were associated with worse profile of ICU patients but not patients' outcomes. CONCLUSION: Acinetobacter in the current study was an increasingly resistant VAP-associated pathogen more than seen in many parts of the world. The current finding may impact local choice of initial empiric antibiotics.

Life-threatening infections in medically immunocompromised patients.

Chronic medical diseases, such as diabetes, chronic obstructive pulmonary disease, chronic kidney disease, cirrhosis, and heart failure, are associated with various immune defects that make affected patients prone to specific infections. This review discusses the epidemiology, pathogenesis, antimicrobial and surgical management, supportive care, and outcome of life-threatening infections associated with common chronic medical diseases.

Even mild hyperlactatemia is associated with increased mortality in critically ill patients.

INTRODUCTION: The clinical significance of elevation of lactate levels within the reference range is not well studied. The objective of this study was to determine the best cutoff threshold for serum lactate within the reference range (0.01 to 2.00 mM) that best discriminated between survivors and nonsurvivors of critical illness and to examine the association between relative hyperlactatemia (lactate above the identified threshold) and mortality. METHODS: This was a retrospective cohort study of adult patients admitted to the medical-surgical intensive care unit (ICU) of a tertiary care academic center. Youden index was calculated to identify the best lactate cutoff threshold that discriminated between survivors and nonsurvivors. Patients with lactate above the identified threshold were defined as having relative hyperlactatemia. Multivariate logistic regression, adjusting for baseline variables, was performed to determine the relationship between the above two ranges of lactate levels and mortality. In addition, a test of interaction was performed to assess the effect of selected subgroups on the association between relative hyperlactatemia and hospital mortality. RESULTS: During the study period, 2,157 patients were included in the study with mean lactate of 1.3 ± 0.4 mM, age of 55.1 ± 20.3 years, and acute physiology and chronic health evaluation (APACHE) II score of 22.1 ± 8.2. Vasopressors were required in 42.4%. Lactate of 1.35 mM was found to be the best cutoff threshold for the whole cohort. Relative hyperlactatemia was associated with increased hospital mortality (adjusted odds ratio (aOR), 1.60, 95% confidence interval (CI) 1.29 to 1.98), and ICU mortality (aOR, 1.66; 95% CI, 1.26 to 2.17) compared with a lactate level of 0.01 to 1.35 mM. This association was consistent among all examined subgroups. CONCLUSIONS: Relative hyperlactatemia (lactate of 1.36 to 2.00 mM) within the first 24 hours of ICU admission is an independent predictor of hospital and ICU mortality in critically ill patients.

Acinetobacter is the most common pathogen associated with late-onset and recurrent ventilator-associated pneumonia in an adult intensive care unit in Saudi Arabia.

BACKGROUND: The guidelines for initial empiric antimicrobial therapy for ventilator-associated pneumonia (VAP) are highly dependent on the type of causative pathogen and the time of diagnosis. The objective of this study was to examine the microbial causes of VAP and describe any variability by the timing of VAP onset and over time. METHODS: A prospective surveillance study was conducted in the adult general intensive care unit of a tertiary care hospital in Riyadh, Saudi Arabia. Microbial isolates obtained from blood and different respiratory specimens of patients diagnosed with VAP (using the US Centers for Disease Control and Prevention definition) between August 2003 and June 2009 were included. RESULTS: A total of 457 pathogens were identified during the study; 380 (83.2%) were associated with primary VAP and 77 (16.8%) were associated with recurrent VAP. Of primary VAP pathogens, 159 (41.8%) were associated with early-onset (<5 days) and 221 (58.2%) were associated with late-onset (≥5 days) VAP. The most common pathogen identified was Acinetobacter spp (26.5%), followed by Pseudomonas aeruginosa (21.7%), Staphylococcus aureus including methicillin-resistant S. aureus (MRSA) (15.3%), Klebsiella spp (6.8%), Haemophilus spp (6.1%), and Enterobacter spp (5.0%). Acinetobacter spp and MRSA were significantly associated with late-onset VAP while Haemophilus spp and Streptococcus pneumoniae were significantly associated with early-onset VAP. Acinetobacter spp was the only pathogen associated with recurrent VAP and its incidence showed a significant increasing trend during the study period. Acinetobacter spp was significantly associated with prolonged ventilation, sedation, and nasogastric intubation. CONCLUSIONS: Acinetobacter baumannii is the most common and increasingly important pathogen associated with VAP in our patients, especially late-onset and recurrent VAP.

The effect of resuscitation fluids on neutrophil-endothelial cell interactions in septic shock.

Fluid resuscitation is essential in the treatment of septic shock. This study examined the effect of resuscitative fluids (RFs) on sepsis-induced neutrophil-endothelial cell interactions. The RFs studied were 0.9% saline (NS), Ringer's lactate (RL), 7.5% saline and dextran-70 (DHS), 5% albumin (AL), and 6% hydroxyethyl starch (HS). Platelets and neutrophils were obtained from normal volunteers, and plasma was obtained from patients with septic shock. Microslides coated with human umbilical endothelial vein cell (HUVEC) and platelet-neutrophil solutions were primed with septic plasma with/without the RF. Neutrophil rolling velocity, leukoaggregation, and neutrophil adherence were determined. Separately, platelet-neutrophil solutions and endothelial cells were exposed to septic plasma with/without RFs, and cellular activation, neutrophil superoxide production, and endothelial cell E-selectin expression were assessed. Ringer's lactate decreased neutrophil rolling velocity and increased aggregation and adherence. Normal saline had no effect on these parameters. Hydroxyethyl starch and AL increased neutrophil rolling velocity and decreased adherence and aggregation when HUVECs were preincubated with the RF. Dextran-70 and 7.5% saline decreased neutrophil-endothelial cell interactions in both HUVECs and platelet/neutrophil preincubated experiments. Ringer's lactate increased activation of neutrophils and platelets, whereas AL decreased their activation. Other than NS, all the RFs increased neutrophil superoxide production. Ringer's lactate increased endothelial cell E-selectin release, whereas AL and HS both decreased its release. These data suggest that fluids used in the resuscitation of septic shock vary in their effects on sepsis-induced neutrophil-endothelial cell interactions. Ringer's lactate amplifies the effects of sepsis, while NS appears to have minimal impact. Dextran-70 and 7.5% saline, AL, and HS in varying degrees decrease sepsis-related neutrophil-endothelial cell interactions and activation.