Selective decontamination of the digestive tract and oropharynx: new findings for an old approach still under discussion

Evaluation of: De Smet ANGA, Kluytmans JAJW, Cooper BS et al. Decontamination of the digestive tract and oropharynx in ICU patients. N. Engl. J. Med. 360(1), 20–31 (2009).

One of the most severe complications that can develop during treatment at an intensive-care unit is nosocomial infections, especially ventilator-associated pneumonia. The fact that these infections are mainly caused by contamination of pathogens from the digestive and oropharyngeal tracts prompted the idea of selectively decontaminating these two organ systems. Although many reports have been published about reducing the prevalence of ventilator-associated pneumonia and, most importantly, mortality by selective decontamination of the digestive and oropharyngeal tract, there are still many open questions. Furthermore, prophylactic decontamination of these two organ systems is not recommended in international guidelines. This article discusses a recently published study involving more than 5000 patients and illuminates the results in the context of other recent findings concerning this topic.     

Prevention of colonization and respiratory infections in long-term ventilated patients by local antimicrobial prophylaxis

In a randomized clinical trial the prophylactic effects of locally administered antimicrobials on quantitative colonization and respiratory infections were studied in intubated patients with an expected period of mechanical ventilation of >6 days. Nineteen patients received 50 mg of polymyxin B and 80 mg of gentamicin distributed among nose, oropharynx and stomach at 6-h intervals, as well as 300 mg of amphotericin B in the oropharynx. Twenty untreated patients served as controls. In the control group colonization by respiratory pathogens was more common (oropharynx 19 vs 6 patients (p(0.001); trachea 19 vs 11 (p(0.01)), and the number as well as the count of the colonizing species was usually higher. Fourteen patients of the control group developed respiratory infections, including nine cases of pneumonia, as compared to four patients with prophylaxis, including one case of pneumonia (p(0.01). Pneumonia-associated deaths were prevented with prophylaxis; however, the overall mortality remained unchanged. Respiratory infections in the prophylaxis group were associated with organisms resistant to the agents used, but the overall occurrence of resistance was not increased, as compared to the control group. We conclude that unrestrained upper airway colonization by respiratory pathogens and respiratory tract infection were causally related. Local antimicrobial prophylaxis proved to be a highly effective strategy for the prevention of potentially life-threatening pneumonias in critically ill patients but in the present study the host setting appeared to be the major determinant of outcome.     

Prognostic importance of gram-negative intestinal colonization preceding pancreatic infection in severe acute pancreatitis

Objectives: To establish, firstly, whether gram-negative (re)-colonization of the gut leads to an increased risk of gram-negative pancreatic infections and whether this event is time-related and, secondly, whether the difference in the quantity and quality of micro-organisms colonizing the digestive tract influences morbidity and mortality. Design: Prospective analysis of the results of systematic semi-quantitative cultures of several body areas taken from patients with severe acute pancreatitis, during a controlled multicenter trial of adjuvant selective decontamination. Setting: Surgical intensive care units of 16 hospitals. Patients: A total of 2159 semi-quantitative cultures from the oropharynx, rectum and pancreatic tissues taken from 90 patients were analyzed. Interventions: Surveillance cultures from the oropharynx and rectum were taken on admission and repeated twice weekly and from the (peri)-pancreatic devitalized tissues (i. e. necrosis) at every relaparotomy and from drainage. Measurements and results: All gram-negative pancreatic infections were preceded by intestinal colonization with the same micro-organisms. The risk of developing a pancreatic infection following gram-negative intestinal colonization (15/42 patients) was significantly higher as compared to patients without gram-negative colonization (0/10 patiens) (p < 0.001) or to patients in whom E. coli was the only intestinal micro-organism cultured (0/30 patients) (p < 0.001). The occurrence of intestinal E. coli did not increase the risk of pancreatic infection. Gram-negative colonization of the rectum and oropharynx significantly correlated with the later development of pancreatic infection: relative risks 73.7 (p < 0.001) and 13.6 (p < 0.001), respectively. However, when both areas were evaluated simultaneously, the rectum was more significant (p < 0.001). The severity of intestinal intestinal colonization until the moment of pancreatic infection showed an increase in time in all 15 patients. In 11 of 15 patients (73 %) these infections occurred within 1 week following the first isolation from the digestive tract. Gram-negative intestinal colonization was associated with a 3.7 fold increased mortality risk (p = 0.004). Conclusions: Gram-negative intestinal colonization, E. coli excepted, is an early prognostic parameter in patients in whom pancreatic infection has not yet occurred and represents a significantly increased risk of pancreatic infections and mortality. Received: 17 June 1997 Accepted: 3 March 1998     

Prevention of ventilator-associated pneumonia,mortality and all intensive care unit acquired infections by topically applied antimicrobial or antiseptic agents: a meta-analysis of randomized controlled trials in intensive care units

Introduction  

Given the high morbidity and mortality attributable to ventilator-associated pneumonia (VAP) in intensive care unit (ICU) patients, prevention plays a key role in the management of patients undergoing mechanical ventilation. One of the candidate preventive interventions is the selective decontamination of the digestive or respiratory tract (SDRD) by topical antiseptic or antimicrobial agents. We performed a meta-analysis to investigate the effect of topical digestive or respiratory tract decontamination with antiseptics or antibiotics in the prevention of VAP, of mortality and of all ICU-acquired infections in mechanically ventilated ICU patients.     

Nosocomial infections: prospective survey of incidence in five French intensive care units

Objective: To assess the incidence and to evaluate the feasibility of inter-unit continuous surveillance of intensive care unit (ICU)-acquired infections. Design: Prospective multicentre, longitudinal, incidence survey. Setting: Five ICUs in university hospitals in western France. Patients: All patients admitted to the ICU during two 3-month periods (1994–1995). Measurements and results: The main clinical characteristics of the patients, ICU-acquired infections, length of exposure to invasive devices and the micro-organisms isolated were analysed. The study included 1589 patients (16 970 patient-days) and the infection rate was 21.6 % (13.1 % of patients). The ventilator-associated pneumonia rate was 9.6 %, sinusitis 1.5 %, central venous catheter-associated infection 3.5 %, central venous catheter-associated bacteraemia 4.8 %, catheter-associated urinary tract infection 7.8 % and bacteraemia 4.5 %. The incidence density rate of ICU-acquired infections was 20.3 ‰ patient-days. Ventilator-associated pneumonia and sinusitis rates were 9.4 and 1.5 ‰ ventilation-days, respectively. Central venous catheter-associated infection and central venous catheter-associated bacteraemia rates were 2.8 and 3.8 ‰ catheter-days, respectively. The catheter-associated urinary tract infection rate was 8.5 ‰ urinary catheter-days and the bacteraemia rate 4.2 ‰ patient-days. Six independent risk factors for ICU-acquired infection were found by stepwise logistic regression analysis: absence of infection on admission, age > 60 years, length of stay, mechanical ventilation, central venous catheter and admission to one particular unit. A total of 410 strains of micro-organisms were isolated, 16.8 % of which were Staphylococcus aureus (58.0 % methicillin-resistant). Conclusion: This prospective study using standardised collection of data on the ICU-acquired infection rate in five ICUs identified six risk factors. It also emphasized the difficulty of achieving truly standardised definitions and methods of diagnosis of such infections. Received: 21 October 1997 Accepted: 4 June 1998     

Characteristics and outcomes of HIV-infected patients in the ICU: impact of the highly active antiretroviral treatment era

Objective To examine whether the introduction of highly active antiretroviral therapy (HAART) has changed the rate of admission, the clinical spectrum, and the mortality of HIV-infected ICU patients.Design Observational study.Setting Infectious diseases ICU in a teaching hospital, Paris, France.Patients All HIV-infected patients admitted during a pre-HAART era (1995–1996; n=189) and a HAART era (1998–2000; n=236).Interventions None.Measurements and results At the HAART era, 79% of patients had derived no or little benefit from the availability of HAART at ICU admission: 44% had no history of antiretroviral (ARV) medications and 35% had failed to respond to ARV. As compared with the pre-HAART era, the rate of hospitalized HIV-infected patients requiring the ICU stay increased (HAART, 5.9% vs pre-HAART, 4.4%; p=0.004). The admission was more likely to occur through the emergency room (45 vs 29%, p=0.0004), and the patients to be foreigners (38.1 vs 28.6%; p=0.04). After adjustment for significant prognostic covariates (AIDS-related tumors at admission, CD4 count <50/mm³, poor functional status (Knaus score C or D), SAPSII, and need for mechanical ventilation), ICU survival was unchanged (adjusted OR=0.613, 95% CI=0.312–1.206), but 3-month survival was significantly improved (adjusted OR=0.57; 95% CI=0.32–0.99; p=0.045).Conclusion The number of HIV-infected patients admitted to the ICU remained high in the HAART era. Underutilization of HAART and limited access to health care are possible explanations. The ICU mortality has remained unchanged, but 3-month mortality has decreased.     

A randomized trial of intravenous glutamine supplementation in trauma ICU patients

Purpose

To evaluate the effect of the intravenous (i.v.) l-alanyl-l-glutamine dipeptide supplementation during 5 days on clinical outcome in trauma patients admitted to the intensive care unit (ICU).

Methods

This was a prospective, randomized, double-blind, multicenter trial. Glutamine was not given as a component of nutrition but as an extra infusion. The primary outcome variable was the number of new infections within the first 14 days.

Results

We included 142 patients. There were no differences between groups in baseline characteristics. Up to 62 % of the patients in the placebo group and 63 % in the treatment group presented confirmed infections (p = 0.86). ICU length of stay was 14 days in both groups (p = 0.54). Hospital length of stay was 27 days in the placebo group and 29 in the treatment group (p = 0.88). ICU mortality was 4.2 % in both groups (p = 1). Sixty percent of the patients presented low glutamine levels before randomization. At the end of the treatment (6th day), 48 % of the patients maintained low glutamine levels (39 % of treated patients vs. 57 % in the placebo group). Patients with low glutamine levels at day 6 had more number of infections (58.8 vs. 80.9 %; p = 0.032) and longer ICU (9 vs. 20 days; p < 0.01) and hospital length of stay (24 vs. 41 days; p = 0.01).

Conclusions

There was no benefit with i.v. l-alanyl-l-glutamine dipeptide supplementation (0.5 g/kg body weight/day of the dipeptide) during 5 days in trauma patients admitted to the ICU. The i.v. glutamine supplementation was not enough to normalize the plasma glutamine levels in all patients. Low plasma glutamine levels at day 6 were associated with a worse outcome.     

Predictive factors of intensive care unit admission in patients with haematological malignancies and pneumonia

Objective To describe early signs at the onset of pneumonia occurring in the haematology ward which could be associated with a transfer to the ICU.Design A 13-month preliminary prospective observational cohort study.Setting Department of haematology and (32-bed) medical intensive care unit (ICU).Patients Fifty-three of 302 patients hospitalised in the haematology ward who developed presumptive clinical evidence of pneumonia were enrolled.Measurements and results At the onset of the clinical evidence of pneumonia (day 1), we compared variables between patients requiring an ICU admission and those who did not. Twenty-four patients (45%) required a transfer to the ICU. Factors associated with ICU admission were: numbers of involved quadrants: 2.3 vs 1, P=0.001 and oxygenation parameters (initial level of O₂ supplementation: 3.5 vs 0.9 l/min, P<0.05), the presence of hepatic failure (58% vs 10%, P<0.01), Gram-negative bacilli isolated in blood culture (7 vs 1, P=0.01). In the multivariate analysis, a decrease of 10% in the SaO₂ and the requirement of nasal supplementary O₂ at the onset of acute respiratory failure increased the risk of admission to MICU, respectively, by 18 and by 14. The overall 6-month mortality rate of the 53 patients was 28%.Conclusion Parameters of oxygenation and radiological score could be associated with this transfer on day 1 of the onset of pneumonia occurrence. A further study should evaluate an earlier selection of this type of patient, followed by an early admission to the MICU, in order to improve ICU outcome.     

Documented and clinically suspected bacterial infection precipitating intensive care unit admission in patients with hematological malignancies: impact on outcome

Objective To assess the impact of documented and clinically suspected bacterial infection precipitating ICU admission on in-hospital mortality in patients with hematological malignancies.Design and setting Prospective observational study in a 14-bed medical ICU at a tertiary university hospital.Patients A total of 172 consecutive patients with hematological malignancies admitted to the ICU for a life-threatening complication over a 4-year period were categorized into three main groups according to their admission diagnosis (documented bacterial infection, clinically suspected bacterial infection, nonbacterial complications) by an independent panel of three physicians blinded to the patients outcome and C-reactive protein levels.Results In-hospital and 6-months mortality rates in documented bacterial infection (n=42), clinically suspected bacterial infection (n=40) vs. nonbacterial complications (n=90) were 50.0% and 42.5% vs. 65.6% (p=0.09 and 0.02) and 56.1% and 48.7% vs. 72.1% (p=0.11 and 0.02), respectively. Median baseline C-reactive protein levels in the first two groups were 23 mg/dl and 21.5 mg/dl vs. 10.7 mg/dl (p<0.001 and p=0.001) respectively. After adjustment for the severity of critical and underlying hematological illness and the duration of hospitalization before admission documented (OR 0.20; 95% CI 0.06–0.62, p=0.006) and clinically suspected bacterial infection (OR 0.18; 95% CI 0.06–0.53, p=0.002) were associated with a more favorable outcome than nonbacterial complications.Conclusions Severely ill patients with hematological malignancies admitted to the ICU because of documented or clinically suspected bacterial infection have a better outcome than those admitted with nonbacterial complications. These patients should receive advanced life-supporting therapy for an appropriate period of time     

Water-based solutions are the best decontaminating fluids for dermal corrosive exposures: A mini review

Abstract

Aim. The intention is to assess whether the fundamental principle (“the solution to pollution is dilution”) should be the guide for the initial medical management of corrosive dermal exposures. Methods. The US National Library of Medicine Pubmed database was searched utilizing all combinations of the search terms “decontamination”, “corrosive”, and “dermal”. A separate search was done specifically related to hydrofluoric acid. These searches found 69 relevant papers. Results. Only four controlled clinical studies comparing early and intensive water decontamination with no or less dilution treatment have been published on human corrosive dermal exposures. Although the authors’ conclusion in the first study of 273 patients was that those that had more intensive water irrigation tended to have less time to skin grafting and shorter periods of hospitalization, the results were not statistically significant. In the second study of 51 patients, those who had “adequate” decontamination (immediate dilution or neutralization therapy) had shortened length of stay (7.2 vs. 16.2 days), lower mortality (9.5% vs. 21%), and fewer skin grafts (19% vs. 36%) despite having slightly greater burn surface area (19.7% vs. 17.2%). However, no statistical analysis was provided. The third and fourth studies were conducted in the same center. In the third study of 35 patients, those who had “immediate” water lavage (done within 10 min of exposure and continued for at least 15 min) had significantly fewer burns that progressed to full thickness (12.5% vs. 63%; p < 0.01) and significantly shorter mean hospital stays (7.7 days vs. 20.5 days; p < 0.01) than those who did not, despite the mean total burn surface area being twice as large in the adequate water decontamination group (12% vs. 6%; p < 0.05). In the fourth study of 83 patients (35 of whom had been reported in the previous study), those who had copious water lavage within 3 min of injury were less likely to progress to full thickness burns (13.5% vs. 60.8%; p < 0.01), had fewer delayed complications (5.4% vs. 30.4%; p < 0.01) and shorter lengths of stay (6.2 vs. 22 days; p < 0.01), compared with those who did not. In a further study, water was compared to the proprietary agent Diphoterine^® in a controlled prospective cohort study of 180 dermal alkali exposures. The Diphoterine^® first group was decontaminated significantly faster than the water first group (median times to irrigation 1 vs. 5 min; p < 0.001). No analysis adjusted for time to decontamination was provided, so the study demonstrated that only those individuals who decontaminated early did better than those who decontaminated later. Conclusions. The data support water as the best decontaminating solution. It has been shown to be efficacious in clinical trials, is widely available, and inexpensive.     

Decontamination of the digestive tract and oropharynx: hospital acquired infections after discharge from the intensive care unit

Objective  To determine the incidence rates of hospital acquired infections (HAI) during the first 14 days after ICU discharge after treatment during ICU-stay with Selective Decontamination of the Digestive tract (SDD), Selective Oropharyngeal Decontamination (SOD) or Standard Care (SC). Design  Prospective observational study. Setting  ICUs in two tertiary care hospitals. Patients  Patients discharged from the ICU to the ward. Interventions  None. Measurements and results  Post-ICU incidences of HAI per 1,000 days at risk were 11.2, 12.9 and 8.3 for patients that had received SDD (n = 296), SOD (n = 286) or SC (n = 289) respectively in ICU, yielding relative risks, as compared to SC, of 1.49 (CI₉₅ 0.9–2.47) for SOD and 1.44 (CI₉₅ 0.87–2.39) for SDD. Incidences of surgical site infections (per 100 surgical procedures) were 4 after SC and 11.8 and 8 after SOD and SDD (p = 0.04). Among patients that succumbed in the hospital after ICU-stay (n = 58) eight (14%) had developed HAI after ICU discharge; 3 of 21 after SDD, 3 of 15 after SOD and 2 of 22 after SC. Conclusions  Incidences of HAI in general wards tended to be higher in patients that had received either SDD or SOD during ICU-stay, but it seems unlikely that these infections have an effect on hospital mortality rates.     

Macrolide-based regimens in absence of bacterial co-infection in critically ill H1N1 patients with primary viral pneumonia

Purpose

To determine whether macrolide-based treatment is associated with mortality in critically ill H1N1 patients with primary viral pneumonia.

Methods

Secondary analysis of a prospective, observational, multicenter study conducted across 148 Intensive Care Units (ICU) in Spain.

Results

Primary viral pneumonia was present in 733 ICU patients with pandemic influenza A (H1N1) virus infection with severe respiratory failure. Macrolide-based treatment was administered to 190 (25.9 %) patients. Patients who received macrolides had chronic obstructive pulmonary disease more often, lower severity on admission (APACHE II score on ICU admission (13.1 ± 6.8 vs. 14.4 ± 7.4 points, p < 0.05), and multiple organ dysfunction syndrome less often (23.4 vs. 30.1 %, p < 0.05). Length of ICU stay in survivors was not significantly different in patients who received macrolides compared to patients who did not (10 (IQR 4–20) vs. 10 (IQR 5–20), p = 0.9). ICU mortality was 24.1 % (n = 177). Patients with macrolide-based treatment had lower ICU mortality in the univariate analysis (19.2 vs. 28.1 %, p = 0.02); however, a propensity score analysis showed no effect of macrolide-based treatment on ICU mortality (OR = 0.87; 95 % CI 0.55–1.37, p = 0.5). Moreover, the sensitivity analysis revealed very similar results (OR = 0.91; 95 % CI 0.58–1.44, p = 0.7). A separate analysis of patients under mechanical ventilation yielded similar results (OR = 0.77; 95 % CI 0.44–1.35, p = 0.4).

Conclusion

Our results suggest that macrolide-based treatment was not associated with improved survival in critically ill H1N1 patients with primary viral pneumonia.     

Procalcitonin (PCT) is useful in predicting the bacterial origin of an acute circulatory failure in critically ill patients

Objective To evaluate the accuracy of procalcitonin (PCT) in predicting bacterial infection in ICU medical and surgical patients. Setting A 10-bed medical surgical unit. Design PCT, C-reactive protein (CRP), interleukin 6 (IL-6) dosages were sampled in four groups of patients: septic shock patients (SS group), shock without infection (NSS group), patients with systemic inflammatory response syndrome related to a proven bacterial infection (infect. group) and ICU patients without shock and without bacterial infection (control group). Results Sixty patients were studied (SS group:n=16, NSS group,n=18, infect. group,n=16, control group,n=10). The PCT level was higher in patients with proven bacterial infection (72±153 ng/ml vs 2.9±10 ng/ml,p=0.0003). In patients with shock, PCT was higher when bacterial infection was diagnosed (89 ng/ml±154 vs 4.6 ng/ml±12,p=0.0004). Moreover, PCT was correlated with severity (SAPS:p=0.00005, appearance of shock:p=0.0006) and outcome (dead: 71.3 g/ml, alive: 24.0 g/ml,p=0.006). CRP was correlated with bacterial infection (p<10⁻⁵) but neither with SAPS nor with day 28 mortality. IL-6 was correlated with neither infection nor day 28 mortality but was correlated with SAPS. Temperature and white blood cell count were unable to distinguish shocked patients with or without infection. Finally, when CRP and PCT levels were introduced simultaneously in a stepwise logistic regression model, PCT remained the unique marker of infection in patients with shock (PCT≥5 ng/ml, OR: 6.2, 95% CI: 1.1–37,p=0.04). Conclusion The increase of PCT is related to the appearance and severity of bacterial infection in ICU patients. Thus, PCT might be an interesting parameter for the diagnosis of bacterial infections in ICU patients.     

Excess ICU mortality attributable to ventilator-associated pneumonia: The role of early vs late onset

Objective To determine the impact of ventilator-associated pneumonia (VAP) on ICU mortality, and whether it is related to time of onset of pneumonia. Design Prospective cohort study. Setting 16-bed medical-surgical ICU at a university-affiliated hospital. Patients and measurements From 2002 to 2003, we recorded patients receiving mechanical ventilation for > 72 h. Patients developing an infection other than VAP were excluded. Patients definitively diagnosed with VAP (n = 40) were cases and patients free of any infection acquired during ICU stay (n = 61) were controls. The VAP-attributed mortality was defined as the difference between observed mortality and predicted mortality (SAPS II) on admission. Results Mechanical ventilation was longer in VAP patients (25 ± 20 vs 11 ± 9 days; p < 0.001), as was ICU stay (33 ± 23 vs 14 ± 12 days; p < 0.001). In the non-VAP group, no difference was found between observed and predicted mortality (27.9 vs 27.4%; p > 0.2). In the VAP group, observed mortality was 45% and predicted mortality 26.5% (p < 0.001), with attributable mortality 18.5%, and relative risk (RR) 1.7 (95% CI 1.12–23.17). No difference was observed between observed and predicted mortality in early-onset VAP (27.3 vs 25.8%; p > 0.20); in late-onset VAP, observed mortality was higher (51.7 vs 26.7%; p < 0.01) with attributable mortality of 25% and an RR 1.9 (95% CI 1.26–2.63). Empiric antibiotic treatment was appropriate in 77.5% of episodes. No differences in mortality were related to treatment appropriateness. Conclusions In mechanically ventilated patients, VAP is associated with excess mortality, mostly restricted to late-onset VAP and despite appropriate antibiotic treatment.     

Clinical significance of thrombocytopenia in patients with septic shock: An observational retrospective study

PurposeWhether thrombocytopenia in critically ill patients accounts for a bystander of severity or drives specific complications is unclear. We addressed the effect of thrombocytopenia on septic shock, with emphasis on intensive care unit (ICU)-acquired bleeding, infections and thrombotic complications.Materials and methodsA retrospective (2008–2019) single-center study of patients with septic shock. Thrombocytopenia was assessed over the first seven days and was defined as severe (nadir <50 G/L), mild (nadir 50–150 G/L) and relative (30% decrease with nadir >150 G/L). Outcomes were ICU mortality and ICU-acquired complications defined by severe bleeding, infections and thrombotic events during the ICU stay.ResultsThe study comprised 1024 patients. Severe, mild and relative thrombocytopenia occurred in 33%, 40% and 9% of patients. The in-ICU mortality rate was 27%, independently associated with severe thrombocytopenia. ICU-acquired infections, hemorrhagic and thrombotic complications occurred in 27.5%, 13.3% and 11.6% of patients, respectively. Patients with severe, mild or relative thrombocytopenia exhibited higher incidences of bleeding events (20.3%, 15.3% and 14.4% vs. 3.6% in non-thrombocytopenic, p < 0.001), infections (35.2%, 21.9% and 33.3% vs. 23.1% in non-thrombocytopenic, p < 0.001) and thrombotic events (14.6%, 10.8% and 17.8% vs. 7.8% in non-thrombocytopenic, p = 0.03). Only severe thrombocytopenia remained independently associated with increased risk of bleeding.ConclusionsSevere thrombocytopenia was independently associated with ICU mortality and increased risk of bleeding, but not with infectious and thrombotic events.     

Selective decontamination of the digestive tract with norfloxacin in the prevention of ICU-acquired infections: a prospective randomized study

The efficacy of relatively cheap regimen of selective decontamination (SDD) was evaluated in a diverse population of ICU patients. Patients requiring prolonged ICU stay (>5 days) were randomly allocated to a treatment group or control group. Control patients (n=52) received perioperative antimicrobial prophylaxis and antibiotic treatment was instituted only on sound clinical and bacteriological criteria. Treated patients (n=48) received gastro-intestinal and oro-pharyngeal decontamination with polymyxin E, norfloxacin, amphotericin B and systemic antibiotic prophylaxis with trimethoprim until decontamination was achieved. The rate of gram-positive infections was not altered by SDD. The incidence of gram-negative respiratory tract, urinary tract and line infections was significantly reduced from 44%, 27% and 15% respectively in the control group to 6%, 4% and 0% in the treatment group. Mortality from nosocomial sepsis and overall mortality were also significantly reduced from 15% and 54% to 0% and 31% respectively. The ICU stay was not reduced by SDD, nor was time on the ventilator or use of therapeutic antibiotics. The reduction in morbidity and mortality was achieved at a relatively low cost.     

Pregabalin for relief of neuropathic pain associated with diabetic neuropathy: A randomized,double‐blind study

Seven published, randomized, placebo‐controlled clinical trials with pregabalin have shown robust efficacy for relief of neuropathic pain from DPN and PHN. An investigation of the efficacy and safety of twice daily pregabalin enrolled 395 adults with painful DPN for ≥1 year in a 12‐week, double‐blind, placebo‐controlled trial. Patients were randomized to placebo, 150, 300, or 600mg/day pregabalin (n=96, 99, 99, and 101). Primary efficacy measure was change from baseline in endpoint mean pain score from patients’ daily pain diaries. Secondary efficacy measures included pain‐related sleep‐interference scores, Patient and Clinical Global Impressions of Change (PGIC, CGIC), and the EuroQOL Health Utilities Index (EQ‐5D). Statistically significant reduction in pain was observed in patients receiving pregabalin 600mg/day, and 46% of patients treated with 600mg/day pregabalin reported ≥50% improvement in mean pain scores from baseline (vs 30% of placebo patients, p=0.036). Number needed to treat to achieve such response was 6.3. Pregabalin 600mg/day was significantly superior to placebo in improving pain‐related sleep‐interference scores (p=0.003), PGIC (p=0.021), and CGIC (p=0.009). (Neither pregabalin 150 nor 300mg/day separated from placebo on these measures, largely because of an atypically large placebo response in one country representing 42% of patients.) All pregabalin dosages were superior to placebo in improving EQ‐5D utility scores (all p≥0.0263 vs placebo). Pregabalin was well tolerated at all dosages; adverse events were generally mild to moderate. Number needed to harm (discontinuation because of adverse events) was 10.3 for pregabalin 600mg/day.     

Prevention of nosocomial infection in critically ill patients by selective decontamination of the digestive tract

Objective: To evaluate the effect of a method of Selective Decontamination of the Digestive Tract (SDD) on colonization, nosocomial infection (NI), bacterial resistance, mortality and economic costs.Design: Randomized, double blind, placebo controlled study.Setting: Polyvalent intensive care unit (ICU) of a tertiary care hospital with 27 beds.Patients: 101 patients with >3 days of mechanical ventilation and >5 days of stay, without infection at the start of the study. 47 belonged to the Treated Group (TG) and 54 to the Placebo Group (PG).Interventions: The TG was given Cefotaxime i.v. (6 g/day) for the first four days and an association of Polymyxin E, Tobramycin and Amphothericin B at the oropharyngeal and gastrointestinal level throughout the whole stay.Results: In the TG, colonization by gram-negative agents at oropharyngeal, tracheal and gastrointestinal level fell significantly. There was a significant drop in the overall, respiratory and urinary NI (26% vs 63%,p<0.001; 15% vs 46%,p<0.001; 9% vs 31%,p<0.01). The overall mortality and NI related mortality was less in the TG (21% vs 44%,p<0.05; 2% vs 20%,p<0.01). The economic costs, mechanical ventilation time and length of stay were similar. The percentage of bacterial isolations resistant to Cefotaxime and Tobramycin was greater in the TG (38% vs 15% and 38% vs 9%,p<0.001).Conclusions: colonization by gram-negative bacilli, NI and the mortality related to it can be modified by SDD. Continuous bacteriological surveillance is necessary.     

Effect of gingival and dental plaque antiseptic decontamination on nosocomial infections acquired in the intensive care unit: a double-blind placebo-controlled multicenter study

OBJECTIVE: To document the effect of gingival and dental plaque antiseptic decontamination on the rate of nosocomial bacteremias and respiratory infections acquired in the intensive care unit (ICU). DESIGN: Prospective, multicenter, double-blind, placebo-controlled efficacy study. SETTING: Six ICUs: three in university hospitals and three in general hospitals. PATIENTS: A total of 228 nonedentulous patients requiring endotracheal intubation and mechanical ventilation, with an anticipated length of stay > or =5 days. INTERVENTIONS: Antiseptic decontamination of gingival and dental plaque with a 0.2% chlorhexidine gel or a placebo gel, three times a day, during the entire ICU stay. MEASUREMENTS AND MAIN RESULTS: Demographic and clinical characteristics, organ function data (Logistic Organ Dysfunction score), severity of condition (Simplified Acute Physiologic Score), and dental plaque status were assessed at baseline and until 28 days. Bacteriologic sampling of dental plaque and saliva was done every 5 days, and blood, tracheal aspirate, and bronchoalveolar lavage cultures were performed when appropriate. The primary efficacy end point was the incidence of bacteremia, bronchitis, and ventilator-associated pneumonia, expressed as a percentage and per 1000 ICU days. All baseline characteristics were similar between the treated and the placebo groups. The incidence of nosocomial infections was 17.5% (13.2 per 1000 ICU days) in the placebo group and 18.4% (13.3 per 1000 ICU days) in the plaque antiseptic decontamination group (not significant). No difference was observed in the incidence of ventilator-associated pneumonia per ventilator or intubation days, mortality, length of stay, and care loads (secondary end points). On day 10, the number of positive dental plaque cultures was significantly lower in the treated group (29% vs. 66%; p < .05). Highly resistant Pseudomonas, Acinetobacter, and Enterobacter species identified in late-onset ventilator-associated pneumonia and previously cultured from dental plaque were not eradicated by the antiseptic decontamination. No side effect was reported. CONCLUSIONS: Gingival and dental plaque antiseptic decontamination significantly decreased the oropharyngeal colonization by aerobic pathogens in ventilated patients. However, its efficacy was insufficient to reduce the incidence of respiratory infections due to multiresistant bacteria.     

Nosocomial bacteremia in a medical-surgical intensive care unit: Epidemiologic characteristics and factors influencing mortality in 111 episodes

Objective To analyze the epidemiology and factors influencing mortality of ICU-acquired bacteremia.Design Prospective clinical study.Setting A medical-surgical ICU in an university hospital.Patients We recorded variables from 111 consecutive ICU-acquired episodes for a 3-year period.Results The attack rate was 1.9 episodes per 100 patientdays. The commonest isolates were coagulase-negative staphylococci,Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. Intravascular catheters were the most frequent source of infection. Overall mortality was 31.5%, and 65.7% of all deaths were directly attributable to infection. Bacteremia from intra-abdominal, lower respiratory tract or unknown origin were associated with a poor prognosis. A logistic regression analysis defined intraabdominal origin (p=0.01, OR=15.7) and presence of shock (p=0.04, OR=3.3) as independently influencing the risk of death. No significant differences were found for the remaining variables studied.Conclusions: Epidemiology and etiology of ICU-acquired bacteremia does not differ seriously in respect to nosocomial bacteremia among unselected populations, although it is associated with a greater incidence and overall mortality. Presence of shock is the most important modificable variable affecting the outcome.