Association Between Minimum Inhibitory Concentration, Beta-lactamase Genes and Mortality for Patients Treated With Piperacillin/Tazobactam or Meropenem From the MERINO Study.

INTRODUCTION: This study aims to assess the association of piperacillin/tazobactam and meropenem minimum inhibitory concentration (MIC) and beta-lactam resistance genes with mortality in the MERINO trial. METHODS: Blood culture isolates from enrolled patients were tested by broth microdilution and whole genome sequencing at a central laboratory. Multivariate logistic regression was performed to account for confounders. Absolute risk increase for 30-day mortality between treatment groups was calculated for the primary analysis (PA) and the microbiologic assessable (MA) populations. RESULTS: In total, 320 isolates from 379 enrolled patients were available with susceptibility to piperacillin/tazobactam 94% and meropenem 100%. The piperacillin/tazobactam nonsusceptible breakpoint (MIC >16 mg/L) best predicted 30-day mortality after accounting for confounders (odds ratio 14.9, 95% confidence interval [CI] 2.8-87.2). The absolute risk increase for 30-day mortality for patients treated with piperacillin/tazobactam compared with meropenem was 9% (95% CI 3%-15%) and 8% (95% CI 2%-15%) for the original PA population and the post hoc MA populations, which reduced to 5% (95% CI -1% to 10%) after excluding strains with piperacillin/tazobactam MIC values >16 mg/L. Isolates coharboring extended spectrum ß-lactamase (ESBL) and OXA-1 genes were associated with elevated piperacillin/tazobactam MICs and the highest risk increase in 30-day mortality of 14% (95% CI 2%-28%). CONCLUSIONS: After excluding nonsusceptible strains, the 30-day mortality difference from the MERINO trial was less pronounced for piperacillin/tazobactam. Poor reliability in susceptibility testing performance for piperacillin/tazobactam and the high prevalence of OXA coharboring ESBLs suggests that meropenem remains the preferred choice for definitive treatment of ceftriaxone nonsusceptible Escherichia coli and Klebsiella.

Severe neurologic syndrome associated with Middle East respiratory syndrome corona virus (MERS-CoV).

BACKGROUND: Since the identification of the first case of infection with the Middle East respiratory syndrome corona virus (MERS-CoV) in Saudi Arabia in June 2012, the number of laboratory-confirmed cases has exceeded 941 cases globally, of which 347 died. The disease presents as severe respiratory infection often with shock, acute kidney injury, and coagulopathy. Recently, we observed three cases who presented with neurologic symptoms. These are so far the first reported cases of neurologic injury associated with MERS-CoV infection. METHODS: Data was retrospectively collected from three patients admitted with MERS-CoV infection to Intensive Care unit (ICU) at King Abdulaziz Medical City, Riyadh. They were managed separately in three different wards prior to their admission to ICU. FINDING: The three patients presented with severe neurologic syndrome which included altered level of consciousness ranging from confusion to coma, ataxia, and focal motor deficit. Brain MRI revealed striking changes characterized by widespread, bilateral hyperintense lesions on T2-weighted imaging within the white matter and subcortical areas of the frontal, temporal, and parietal lobes, the basal ganglia, and corpus callosum. None of the lesions showed gadolinium enhancement. INTERPRETATION: CNS involvement should be considered in patients with MERS-CoV and progressive neurological disease, and further elucidation of the pathophysiology of this virus is needed.

Outcome of tracheotomized patients following reintubation.

OBJECTIVE: To evaluate the outcome of tracheotomized patients after reintubation. METHOD: Secondary analysis from a prospective, multicenter and observational study including 36 Intensive Care Units (ICUs) from 8 countries. PATIENTS: A total of 180 patients under mechanical ventilation for more than 48 hours, extubated and reintubated within 48 hours. INTERVENTIONS: None. OUTCOMES: ICU mortality, length of ICU stay, organ failure. RESULTS: Fifty-two patients (29%) underwent tracheotomy after reintubation. The median time from reintubation to tracheotomy was 2.5 days (interquartile range (IQR) 1-8 days). The length of ICU stay was significantly longer in the tracheotomy group compared with the group without tracheotomy (median time 25 days, IQR 17-43 versus 16.5 days (IQR 11-25); p<0.001). ICU mortality in the tracheotomy group was not significantly different (31% versus 27%; p 0.57). CONCLUSIONS: In our cohort of reintubated patients, tracheotomy is a common procedure in the ICU. Patients with tracheotomy had an outcome similar to those without tracheotomy.

The epidemiology of the first described carbapenem-resistant Klebsiella pneumoniae outbreak in a tertiary care hospital in Saudi Arabia: how far do we go?

The purpose of this investigation was to describe the first documented carbapenem-resistant Klebsiella pneumoniae (CRKP) outbreak in a tertiary care facility in Saudi Arabia. We initiated a prospective study to follow all cases of CRKP as well as the active surveillance of patients in areas where cases were identified. We also conducted a retrospective review of the microbiology database for any missed cases of CRKP. Pulsed field gel electrophoresis (PFGE) was conducted for the available CRKP isolates. During March 2010, a cluster of eight CRKPs was detected primarily in the adult intensive care unit (ICU). Patients with CRKPs were put under strict contact isolation, along with appropriate infection control measures. A retrospective review of K. pneumoniae isolates over the previous 6 months revealed two more CRKPs. The PFGE results during the outbreak period showed that the majority of strains were genetically indistinguishable or closely related. The majority of patients had prolonged hospital stay (91%), indwelling devices (81%), surgical procedures (74%), carbapenem use (62%), and colonization/infection with other multiple drug-resistant organisms (MDROs) (57%). Two-fifths of patients with CRKP had clinical infection and 38% died during the current hospitalization. Contact isolation, hand hygiene, environmental cleaning, and staff education may control CRKP outbreak in the acute care setting, but did not prevent endemicity.

Influence of body mass index on outcome of the mechanically ventilated patients.

BACKGROUND: There are limited data on the impact of body mass index on outcomes in mechanically ventilated patients. METHODS: Secondary analysis of a cohort including 4698 patients mechanically ventilated. Patients were screened daily for management of mechanical ventilation, complications (acute respiratory distress syndrome, sepsis, ventilator associated pneumonia, barotrauma), organ failure (cardiovascular, respiratory, renal, hepatic, haematological) and mortality in the intensive care unit. To estimate the impact of body mass index on acute respiratory distress syndrome and mortality, the authors constructed models using generalised estimating equations (GEE). RESULTS: Patients were evaluated based on their body mass index: 184 patients (3.7%) were underweight, 1995 patients (40%) normal weight, 1781 patients (35.8%) overweight, 792 patients (15.9%) obese and 216 patients (4.3%) severely obese. Severely obese patients were more likely to receive low tidal volume based on actual body weight but high volumes based on predicted body weight. In obese patients, the authors observed a higher incidence of acute respiratory distress syndrome and acute renal failure. After adjustment, the body mass index was significantly associated with the development of acute respiratory distress syndrome: compared with normal weight; OR 1.69 (95% CI 1.07 to 2.69) for obese and OR 2.38 (95% CI 1.15 to 4.89) for severely obese. There were no differences in outcomes (duration of mechanical ventilation, length of stay and mortality in intensive care unit and hospital) based on body mass index categories. CONCLUSIONS: In this cohort, obese patients were more likely to have significant complications but there were no associations with increased mortality.

Neuromuscular blockade in patients with ARDS: a rapid practice guideline.

The aim of this Intensive Care Medicine Rapid Practice Guideline (ICM-RPG) is to formulate an evidence-based guidance for the use of neuromuscular blocking agents (NMBA) in adults with acute respiratory distress syndrome (ARDS). The panel comprised 20 international clinical experts from 12 countries, and 2 patient representatives. We adhered to the methodology for trustworthy clinical practice guidelines and followed a strict conflict of interest policy. We convened panelists through teleconferences and web-based discussions. Guideline experts from the guidelines in intensive care, development, and evaluation Group provided methodological support. Two content experts provided input and shared their expertise with the panel but did not participate in drafting the final recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty of evidence and grade recommendations and suggestions. We used the evidence to decision framework to generate recommendations. The panel provided input on guideline implementation and monitoring, and suggested future research priorities. The overall certainty in the evidence was low. The ICM-RPG panel issued one recommendation and two suggestions regarding the use of NMBAs in adults with ARDS. Current evidence does not support the early routine use of an NMBA infusion in adults with ARDS of any severity. It favours avoiding a continuous infusion of NMBA for patients who are ventilated using a lighter sedation strategy. However, for patients who require deep sedation to facilitate lung protective ventilation or prone positioning, and require neuromuscular blockade, an infusion of an NMBA for 48 h is a reasonable option.

Association of protein intake with the outcomes of critically ill patients: a post hoc analysis of the PermiT trial.

Background: The optimal amount of protein intake in critically ill patients is uncertain. Objective: In this post hoc analysis of the PermiT (Permissive Underfeeding vs. Target Enteral Feeding in Adult Critically Ill Patients) trial, we tested the hypothesis that higher total protein intake was associated with lower 90-d mortality and improved protein biomarkers in critically ill patients. Design: In this post hoc analysis of the PermiT trial, we included patients who received enteral feeding for ≥3 consecutive days. Using the median protein intake of the cohort as a cutoff, patients were categorized into 2 groups: a higher-protein group (>0.80 g · kg-1 · d-1) and a lower-protein group (≤0.80 g · kg-1 · d-1). We developed a propensity score for receiving higher protein. Primary outcome was 90-d mortality. We also compared serial values of prealbumin, transferrin, 24-h urinary nitrogen, and 24-h nitrogen balance on days 1, 7, and 14. Results: Among the 729 patients included in this analysis, the average protein intake was 0.8 ± 0.3 g · kg-1 · d-1 [1.0 ± 0.2 g · kg-1 · d-1 in the higher-protein group (n = 365) and 0.6 ± 0.2 g · kg-1 · d-1 in the lower-protein group (n = 364); P < 0.0001]. There was no difference in 90-d mortality between the 2 groups [88/364 (24.2%) compared with 94/363 (25.9%), propensity score-adjusted OR: 0.80; 95% CI: 0.56, 1.16; P = 0.24]. Higher protein intake was associated with an increase in 24-h urea nitrogen excretion compared with lower protein intake, but without a significant change in prealbumin, transferrin, or 24-h nitrogen balance. Conclusions: In the PermiT trial, a moderate difference in protein intake was not associated with lower mortality. Higher protein intake was associated with increased nitrogen excretion in the urine without a corresponding change in prealbumin, transferrin, or nitrogen balance. Protein intake needs to be tested in adequately powered randomized controlled trials targeting larger differences in protein intake in high-risk populations.

Critical care medicine in Saudi Arabia.

Critical care medicine remains underdeveloped in many parts of the world. In Saudi Arabia, there have been major developments in the past 2-3 decades. The purpose of this review is to give an account of the current status of critical care practice (including services provided during the haj season) and training in Saudi Arabia using examples of primary, secondary and tertiary care hospitals. The future needs of the profession are also addressed.

Learning from defects using a comprehensive management system for incident reports in critical care.

Incident reporting systems are often used without a structured review process, limiting their utility to learn from defects and compromising their impact on improving the healthcare system. The objective of this study is to describe the experience of implementing a Comprehensive Management System (CMS) for incident reports in the ICU. A physician-led multidisciplinary Incident Report Committee was created to review, analyse and manage the department incident reports. New protocols, policies and procedures, and other patient safety interventions were developed as a result. Information was disseminated to staff through multiple avenues. We compared the pre- and post-intervention periods for the impact on the number of incident reports, level of harm, time needed to close reports and reporting individuals. A total of 1719 incidents were studied. ICU-related incident reports increased from 20 to 36 incidents per 1000 patient days (P=0.01). After implementing the CMS, there was an increase in reporting 'no harm' from 14.2 to 28.1 incidents per 1000 patient days (P<0.001). There was a significant decrease in the time needed to close incident report after implementing the CMS (median of 70 days [Q1-Q3: 26-212] versus 13 days [Q1-Q3: 6-25, P<0.001]). A physician-led multidisciplinary CMS resulted in significant improvement in the output of the incident reporting system. This may be important to enhance the effectiveness of incident reporting systems in highlighting system defects, increasing learning opportunities and improving patient safety.

Appropriate and timely antimicrobial therapy in cirrhotic patients with spontaneous bacterial peritonitis-associated septic shock: a retrospective cohort study.

BACKGROUND: Spontaneous bacterial peritonitis (SBP)-associated septic shock carries significant mortality in cirrhosis. AIM: To determine whether practice-related aspects of antimicrobial therapy contribute to high mortality. METHODS: Retrospective cohort study of all (n = 126) cirrhotics with spontaneous bacterial peritonitis (neutrophil count >250 or positive ascitic culture)-associated septic shock (1996-2011) from an international, multicenter database. Appropriate antimicrobial therapy implied either in vitro activity against a subsequently isolated pathogen (culture positive) or empiric management consistent with broadly accepted norms (culture negative). RESULTS: Overall hospital mortality was 81.8%. Comparing survivors (n = 23) with non-survivors (n = 103), survivors had lower Acute Physiology and Chronic Health Evaluation (APACHEII) (mean ± s.d.; 22 ± 7 vs. 32 ± 8) and model for end-stage liver disease (MELD) (24 ± 9 vs. 34 ± 11) scores and serum lactate on admission (4.9 ± 3.1 vs. 8.9  ± 5.3), P < 0.001 for all. Survivors were less likely to receive inappropriate initial antimicrobial therapy (0% vs. 25%, P = 0.013) and received appropriate antimicrobial therapy earlier [median 1.8 (1.1-5.2) vs. 9.5 (3.9-14.3) h, P < 0.001]. After adjusting for covariates, APACHEII [OR, odds ratio 1.45 (1.04-2.02) per 1 unit increment, P = 0.03], lactate [OR 2.34 (1.04-5.29) per unit increment, P = 0.04] and time delay to appropriate antimicrobials [OR 1.86 (1.10-3.14) per hour increment, P = 0.02] were significantly associated with increased mortality. CONCLUSIONS: Cirrhotic patients with septic shock secondary to spontaneous bacterial peritonitis have high mortality (>80%). Each hour of delay in appropriate antimicrobial therapy was associated with a 1.86 times increased hospital mortality. Admission APACHEII and serum lactate also significantly impacted hospital mortality. Earlier initiation of appropriate antimicrobial therapy could substantially improve outcome.

Faecal toxin and severity of antibiotic-associated pseudomembranous colitis.

The relationship between faecal toxin titre, histological evidence of pseudomembrane in the rectum, and severity of antibiotic-associated colitis has been analysed from data on 62 patients whose faeces contained Clostridium difficile toxin. There was a significant correlation between a toxin titre of 6400 or more and the presence of pseudomembrane (p less than 005). There was no correlation between toxin titre, duration of diarrhoea, total white cell count, temperature, serum albumin or serum orosomucoid concentrations. There was, however, a significant correlation between the presence of rectal pseudomembrane and duration of diarrhoea (p less than 0.005). Exposure to clindamycin or lincomycin was also associated with a significantly higher toxin titre than that seen in patients who were given other antibiotics. The duration of diarrhoea of diarrhoea was not longer and rectal pseudomembrane did not occur more often in the patients who had received clindamycin or lincomycin.

Daytime blood pressure elevation after nocturnal hypoxia.

The purpose of this study was to investigate whether nocturnal hypoxia causes daytime blood pressure (BP) elevation. We hypothesized that overnight exposure to hypoxia leads the next morning to elevation in BP that outlasts the hypoxia stimulus. We studied the effect on BP of two consecutive night exposures to hypobaric hypoxia in 10 healthy normotensive subjects. During the hypoxia nights, subjects slept for 8 h in a hypobaric chamber at a simulated altitude of 4,000 m (barometric pressure = 462 mmHg). Arterial O(2) saturation and electrocardiogram were monitored throughout the night. For 30 min before the nocturnal simulated ascent and for 4 h after return to baseline altitude the next morning, BP was measured every 5 min while the subject was awake. The same measurements were made before and after 2 normoxic nights of sleep in the hypobaric chamber at ambient barometric pressure (745 mmHg). Principal components analysis was applied to evaluate patterns of BP response after the second night of hypoxia and normoxia. A distinct pattern of diastolic BP (DBP) elevation was observed after the hypoxia night in 9 of the 10 subjects but in none after the normoxia night. This pattern showed a mean increase of 4 mmHg in DBP compared with the presleep-awake baseline in the first 60 min and a return to baseline by 90 min. We conclude that nocturnal hypoxia leads to a carryover elevation of daytime DBP.

Adrenal insufficiency, recurrent bacteremia, and disseminated abscesses caused by Nocardia asteroides in a patient with acquired immunodeficiency syndrome.

Nocardia asteroides is an opportunistic pathogen of increasing incidence in human immunodeficiency virus (HIV)-infected persons. The lungs are the most common site of infection, followed by the brain; involvement of other extrapulmonary sites is less common. We describe a patient with acquired immunodeficiency syndrome who presented with a number of unique manifestations of nocardial infection: the first reported case of bilateral adrenal abscesses with adrenal insufficiency, the first case of a renal abscess due to N. asteroides alone, and the first case of recurrent, symptomatic bacteremia. A review of the literature on nocardial infections in HIV-positive individuals is presented.

Metronidazole prophylaxis in acute mural appendicitis: failure of a single intra-operative infusion to reduce wound infection.

The efficacy of a single 500 mg intravenous intra-operative dose of metronidazole in the prevention of postoperative wound infection, following appendicectomy for acute mural appendicitis, was studied in a prospective randomized placebo controlled trial. Fourteen of the 96 patients (14.6%) in the metronidazole group and 13 of the 94 in the placebo group (13.8%) developed postoperative wound infection. Late sepsis was noted in 4 out of the 96 patients in the metronidazole group and in one of the 94 patients in the placebo group. This study suggests that a single intra-operative dose of metronidazole dose not reduce the incidence of postoperative wound infection following appendicectomy for acute mural appendicitis.

Anal pressures in hemorrhoids and anal fissure.

Maximal anal pressures have been measured after proctoscopy in 145 patients with hemorrhoids, 48 patients with anal fissure, and 78 asymptomatic control subjects. Anal pressures in patients with hemorrhoids (106 +/- 40 cm H2O) and anal fissure (130 +/- 43 cm H2O) were very significantly higher than those of controls (88 +/- 34 cm H2O) (P less than 0.001). Because patients with anal fissure have high anal pressures, these patients should benefit from manual dilatation of the anus or lateral subcutaneous sphincterotomy; however, only young male patients with hemorrhoids have anal pressures that are significantly higher than age- and sex-matched controls. Digital assessment and the two finger test are unreliable indicators of high anal pressure. These results indicate that measurement of anal pressure is useful in assessing the suitability of manual dilatation or sphincterotomy in the treatment of hemorrhoids.

Importance of adding neomycin to metronidazole for bowel preparation.

A prospective randomized trial has investigated whether it is necessary to add oral neomycin to oral metronidazole as a means of preventing sepsis in elective colonic resection. Seventy-three patients completed the study; 41 received metronidazole and placebo neomycin and 32 received metronidazole and active neomycin. There was a significant reduction in the incidence of wound infection in patients receiving neomycin and metronidazole (22%) compared with metronidazole alone (51%, P<0.02). There was also a significant reduction in anaerobic infections in the group receiving metronidazole and neomycin compared with metronidazole alone (P<0.05). These results indicate that oral metronidazole alone is of no benefit for patients requiring elective colonic operations and that if oral metronidazole is advised it should always be given in combination with oral neomycin.

Intestinal obstruction in Khartoum.

The pattern of intestinal obstruction at Khartoum Teaching Hospital was reviewed in this study which included 239 patients. 170 of them were males and 68 were females. Their ages ranged from two days to 95 years (mean 31.4 +/- 5.3 years). The commonest causes of intestinal obstruction were strangulated external hernias (27.7%), intestinal adhesions (21%), intussusception (12%) and sigmoid volvulus (11%). Less frequent causes were paralytic ileus, large bowel tumours, peritoneal bands and Hirschsprung's disease. Of the strangulated hernias, inguinal hernia (70%) was the most frequent type of hernia seen, followed by paraumbilical hernia (20%). Previous appendicectomy (40%) and laparotomy for abdominal trauma (20%) were the commonest causes of adhesive intestinal obstruction. The mortality rate of intestinal obstruction was 19.7%. This high mortality is attributed to delayed presentation, fluid and electrolyte imbalance, intestinal ischaemia and gangrene. This could be minimised by health education, adequate preoperative preparation, meticulous surgical technique and good postoperative care.

Physicians declining patient enrollment in a critical care trial: a case study in thromboprophylaxis.

PURPOSE: To analyze the frequency, rationale and determinants of attending physicians requesting that their eligible patients not be approached for participation in a thromboprophylaxis trial. METHODS: Research personnel in 67 centers prospectively documented eligible non-randomized patients due to physicians declining to allow their patients to be approached. RESULTS: In 67 centers, 3,764 patients were enrolled, but 1,460 eligible patients had no consent encounter. For 218 (14.9 %) of these, attending physicians requested that their patients not be approached. The most common reasons included a high risk of bleeding (31.2 %) related to fear of heparin bioaccumulation in renal failure, the presence of an epidural catheter, peri-operative status or other factors; specific preferences for thromboprophylaxis (12.4 %); morbid obesity (9.6 %); uncertain prognosis (6.4 %); general discomfort with research (3.7 %) and unclear reasons (17.0 %). Physicians were more likely to decline when approached by less experienced research personnel; considering those with[10 years of experience as the reference category, the odds ratios (OR) for physician refusals to personnel without trial experience was 10.47 [95 % confidence interval (CI) 2.19-50.02] and those with less than 10 years experience was 1.72 (95 % CI 0.61-4.84). Physicians in open rather than closed units were more likely to decline (OR 4.26; 95 % CI 1.27-14.34). Refusals decreased each year of enrollment compared to the pilot phase. CONCLUSIONS: Tracking, analyzing, interpreting and reporting the rates and reasons for physicians declining to allow their patients to be approached for enrollment provides insights into clinicians' concerns and attitudes to trials. This information can encourage physician communication and education, and potentially enhance efficient recruitment.