Colistin resistance in gram-negative bacteria during prophylactic topical colistin use in intensive care units

Purpose

Topical use of colistin as part of selective digestive decontamination (SDD) and selective oropharyngeal decontamination (SOD) has been associated with improved patient outcome in intensive care units (ICU), yet little is known about the risks of colistin resistance. We quantified effects of selective decontamination on acquisition of colistin-resistant gram-negative bacteria (GNB) using data from a cluster-randomized study and a single-centre cohort.

Methods

Acquisition of colistin-resistant GNB and conversion from susceptible to resistance in GNB was determined in respiratory samples [from patients receiving SDD (n = 455), SOD (n = 476), or standard care (SC) (n = 315)], and in rectal swabs from 1,840 SDD-patients. Genotyping of converting isolates was performed where possible.

Results

The respiratory tract acquisition rates of colistin-resistant GNB were comparable during SDD, SOD, and SC and ranged from 0.7 to 1.1/1,000 patient-days at risk. Rectal acquisition rates during SDD were <3.3/1,000 days at risk. In patients with respiratory tract GNB carriage, conversion rates were 3.6 and 1.1/1,000 patient-days at risk during SDD and SC, respectively, (p > 0.05). In patients with rectal GNB carriage conversion rates during SDD were 5.4 and 3.2/1,000 days at risk and 15.5 and 12.6/1,000 days at risk when colonized with tobramycin-resistant GNB.

Conclusions

Acquisition rates with colistin-resistant GNB in the respiratory tract were low and comparable with and without topical use of colistin. Rates of acquisition of colistin-resistant GNB during SDD were—in ICUs with low endemicity of antibiotic resistance—<2.5/1,000 days at risk, but were fivefold higher during persistent GNB colonization and 15-fold higher during carriage with tobramycin-resistant GNB.     

Infection prevention in intensive care by selective decontamination of the digestive tract

Infection prevention in the ICU by SDD is based on new insights in the pathogenesis of infections. The recognition that the colonization defense of the oropharynx and gastrointestinal tract is severely impaired in critically ill patients plays a crucial role in this concept.Selective decontamination of the digestive tract is a technique aiming at the elimination of aerobic, potentially pathogenic microorganisms from the oropharynx and gastrointestinal tract with topical nonabsorbable antibiotics. It is based on the following observations: the indigenous flora is seldom involved in infections and has important physiologic functions; there are major differences in the intrinsic pathogenic potential of microorganisms; and colonization and infection of the respiratory and urinary tract and wounds are generally preceded by colonization of the oropharynx or gastrointestinal tract.Several studies have shown that SDD is very effective in preventing acquired infections in intensive care. Although in polytrauma patients the outcome seems to improve with SDD, in general surgical patients, the expected reduction of mortality with the prevention of nosocomial infections has not been found. However, none of the studies was designed for that purpose. The most important conclusion is that many patients are admitted in the ICU with potentially preventable infections and that SDD might be more useful in these patients if applied in an earlier stage. Unlike previous attempts with topical antibiotics, emergence of resistance has not been observed. On the contrary, the prevalence of multiresistant strains seems to decrease with the routine application of this regimen. It has been shown that outbreaks with multiresistant gram-negative bacilli can be controlled by SDD.More studies are required to investigate the potential indications and consequences of this technique.     

Selective digestive decontamination by erythromycin-base in a polyvalent intensive care unit

Objective

To study the effect of selective digestive tract decontamination by erythromycin-base on the incidence of carriage and infection with MREnterobacteriaceae producing an extended spectrum beta-lactamase (ESB).

Design

After a 10-week prospective survey to ascertain the baseline incidence in two bays (1 and 3) of the same ICU, bay 1 was compared with bay 3 during a further survey of 6 moths. The patients in bya 1. received erythromycin-base.

Setting

Two non-contiguous bays, 1 and 3, of 4 beds, in the same polyvalent ICU of a university hospital.

Patient

Consecutive patients with unit stay longer than 2 days; 34 patients were included during the control period, 43 in bay 1 (decontamination) and 46 in bay 3 (control) during the trial period.

Intervention

Erythromycin-base, 1 g t.i.d. in powder form administered by gastric tube to patients in bay 1 from admission to discharge.

Measurements and results

Digestive tract carriage was monitored by cultures of gastric and rectal swab specimens, sampled twice a week.Enterobacteriaceae were isolated on Drigalski agar with incorporated ceftazidime (4 mg/l). In bay 1 there was a decrease in ESB producingEnterobacteriaceae (23% vs 10%,p=0.0004) from rectal swab, especially inK. pneumoniae (15% vs 2%,p=10^?5), during the decontamination period in comparison to the control period. During the trial period the only differences observed between bays 1 and 3 were in the gastric samples:K. pneumoniae were less often isolated in bay 1 than in bay 3 (0% vs 3%,p=0.03). Intestinal carriage with multiresistantEnterobacteriaceae occurred in 28% patients in bay 1 and 30% patients in bay 3 during the trial period (p=0.79). Erythromycin-base did not delay the carriage by patients in bay 1 (log rank testp=0.42).

Conclusion

Erythromycin-base was not effective in preventing digestive tract carriage due toEnterobacteriaceae resistant to third generation cephalosporin by production of chromosomal cephalosporinase. The decrease in isolates containingK. pneumoniae in bay 1 cannot be definitively attributed to erythromycin-base, since the number of this species in bay 3 was low.     

Oropharyngeal decontamination in intensive care patients: less is not more

Ventilator-associated pneumonia (VAP) is a common cause of morbidity, antibiotic use, increased length of stay and, possibly, increased mortality in ICU patients. Colonization of the oropharyngeal cavity with potentially pathogenic micro-organisms is instrumental in the pathogenesis of VAP, and selective oropharyngeal decontamination (SOD) with antibiotics (AB-SOD) or antiseptics, such as chlorhexidine gluconate (CHX-SOD), has been associated with reduced incidences of VAP. In a recent issue of Critical Care Scannapieco and colleagues investigated differences in oropharyngeal colonization between mechanically ventilated patients receiving oropharyngeal decontamination with 0.12% CHX-SOD either once or twice daily compared to placebo. CHX-SOD was associated with a reduction in Staphylococcus aureus colonization, but the study was underpowered to demonstrate a reduction in VAP incidence. We urgently need well-designed and adequately powered studies to evaluate the potential benefits of CHX-SOD on patient outcome in ICUs.     

Paradoxical ventilator associated pneumonia incidences among selective digestive decontamination studies versus other studies of mechanically ventilated patients: benchmarking the evidence base

Introduction  

Selective digestive decontamination (SDD) appears to have a more compelling evidence base than non-antimicrobial methods for the prevention of ventilator associated pneumonia (VAP). However, the striking variability in ventilator associated pneumonia-incidence proportion (VAP-IP) among the SDD studies remains unexplained and a postulated contextual effect remains untested for.     

Probiotics versus antibiotic decontamination of the digestive tract: infection and mortality

Purpose  

Selective decontamination of the digestive tract (SDD) has been shown to decrease the infection rate and mortality in intensive care units (ICUs); Lactobacillus plantarum 299/299v plus fibre (LAB) has been used for infection prevention and does not harbour the potential disadvantages of antibiotics. The objective was to assess whether LAB is not inferior to SDD in infection prevention.     

Incidence and risk factors of device-associated infections and associated mortality at the intensive care in the Dutch surveillance system

Objective To examine the incidence of and risk factors for device-associated infections and associated mortality. Design and setting Prospective surveillance-based study in ICUs of 19 hospitals in The Netherlands. Patients The study included 2,644 patients without infection at admission during 1997–2000, staying in the ICU for at least 48 h. Measurements and results The occurrence of ventilator-associated pneumonia (VAP), central venous catheter (CVC) related bloodstream infection (CR-BSI), urinary catheter-associated urinary tract infection (CA-UTI) and risk factors was monitored. Of the ventilated patients 19% developed pneumonia (25/1,000 ventilator days); of those with a central line 3% developed CR-BSI (4/1,000 CVC days,) and of catheterized patients 8% developed CA-UTI (9/1,000 catheter days). Longer device use increased the risk for all infections, especially for CR-BSI. Independent risk factors were sex, immunity, acute/elective admission, selective decontamination of the digestive tract, and systemic antibiotics at admission, dependent upon the infection type. Crude mortality significantly differed in patients with and without CR-BSI (31% vs. 20%) and CA-UTI (27% vs. 17%) but not for VAP (26% vs. 23%). Acquiring a device-associated infection was not an independent risk factor for mortality. Being in need of ventilation or a central line, and the duration of this, contributed significantly to mortality, after adjusting for other risk factors. Conclusions Device use was the major risk factor for acquiring VAP, CR-BSI and CA-UTI. Acquiring a device-associated infection was not an independent risk factor for mortality, but device use in itself was. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users. This work was performed within the project "Prevention of Hospital Infections Through Surveillance (PREZIES) at the National Institute for Public Health and the Environment, RIVM, Bilthoven, The Netherlands. This article is discussed in the editorial available at: .     

Six-month prognosis of patients with lung cancer admitted to the intensive care unit

Background

Intensive care unit (ICU) admission of patients with lung cancer remains debated because of the poor short-term prognosis. However, ICU admission of such patients should also be assessed on the possibility to administer specific anticancer treatment and the long-term outcome thereafter.

Objectives

To identify predictive factors of hospital and 6-month mortality in critically ill lung-cancer patients.

Design and setting

Retrospective study conducted in the ICU of a university hospital.

Patients

One hundred five consecutive lung-cancer patients included between 1 January 1997 and 31 December 2006.

Interventions

None.

Results

Of the 105 patients (mean age 64.8 years), 87 (83%) had a non-small cell lung cancer (NSCLC). Extensive disease was diagnosed in 85 patients (83%) (NSCLC stages IIIB and IV or disseminated small cell lung cancer). The main reasons for ICU admission were acute respiratory failure (59%) and/or hemoptysis (45%). Forty-three patients (41%) needed mechanical ventilation (MV). The ICU, hospital and 6-month mortality rates were 43, 54 and 73%, respectively. A performance status (PS) ≥2 [odds ratio OR = 3.6 (95% confidence interval CI (1.5–8.7)] and acute respiratory failure [OR = 3.5 (95% CI (1.5–8.4)] predicted hospital mortality. In a multivariate Cox model, the cancer progression [hazard ratio HR = 6.1 (95% CI 2.2–17)] and the need for MV [HR = 3.6 (95% CI 1.35–9.4)] were independently associated with 6-month mortality. Two-thirds of the ICU survivors were able to receive anticancer treatment.

Conclusions

ICU admission should be considered in selected patients with lung cancer (PS <2, no cancer disease progression).     

Ventilator-associated pneumonia: current status and future recommendations

Objective  

Ventilator-associated pneumonia (VAP) is a common hazardous complication in ICU patients. The aim of the current review is to give an update on the current status and future recommendations for VAP prevention.     

An open-labelled randomized controlled trial comparing costs and clinical outcomes of open endotracheal suctioning with closed endotracheal suctioning in mechanically ventilated medical intensive care patients

Purpose

Closed endotracheal suctioning (CES) may impact ventilator-associated pneumonia (VAP) risk by reducing environmental contamination. In developing countries where resource limitations constrain the provision of optimal bed space for critically ill patients, CES assumes greater importance.

Materials and Methods

In this prospective, open-labeled, randomized controlled trial spanning 10 months, we compared CES with open endotracheal suctioning (OES) in mechanically ventilated patients admitted to the medical intensive care unit (ICU) of a university-affiliated teaching hospital. Patients were followed up from ICU admission to death or discharge from hospital. Primary outcome was incidence of VAP. Secondary outcomes included mortality, cost, and length of stay.

Results

Two hundred patients were recruited, 100 in each arm. The incidence of VAP was 23.5%. Closed endotracheal suctioning was associated with a trend to a reduced incidence of VAP (odds ratio, 1.86; 95% confidence interval, 0.91-3.83; P = .067). A significant benefit was, however, observed with CES for late-onset VAP (P = .03). Mortality and duration of ICU and hospital stay were similar in the 2 groups. The cost of suction catheters and gloves was significantly higher with CES (Rs 272 [US $5.81] vs Rs 138 [US $2.94], P < .0001). Nine patients need to be treated with CES to prevent 1 VAP (95% confidence interval, −0.7 to 22).

Conclusions

In the ICU setting in a developing country, CES may be advantageous in reducing the incidence of VAP, particularly late-onset VAP. These results mandate further studies in this setting before specific guidelines regarding the routine use of CES are proposed.     

Hypothermia does not increase the risk of infection: a case control study

Introduction  

Hypothermia may improve outcome in patients after traumatic brain injury, especially when hypothermia is maintained for more than 48 hours. In the acute phase, patients with severe brain injury are more vulnerable to infections. Prolonged hypothermic treatment may further enhance the risk of infection. Selective decontamination of the digestive tract (SDD) reduces the risk of respiratory tract infections. The aim of this study was to investigate the incidence of infections in patients treated with hypothermia and normothermia while receiving SDD.     

Oral decontamination is cost-saving in the prevention of ventilator-associated pneumonia in intensive care units

OBJECTIVE: Although the development of ventilator-associated pneumonia (VAP) is assumed to increase costs of intensive care unit stay, it is unknown whether prevention of VAP by means of oropharyngeal decontamination is cost-effective. Because of wide ranges of individual patient costs, crude cost comparisons did not show significant cost reductions. DESIGN: Based on actual cost data of 181 individual patients included in a former randomized clinical trial, cost-effectiveness of prevention of VAP was determined using a decision model and univariate sensitivity analyses, and bootstrapping was used to assess the impact of variability in the various outcomes. DATA SOURCE: Published data on prevention of VAP by oropharyngeal decontamination, which resulted in a relative risk for VAP of 0.45, with a baseline rate of VAP of 29% among control patients. The mean costs of the intervention were 351 dollars per patient (32 dollars per patient per day). All other costs were derived from the hospital administrative database for all individual patients. RESULTS OF BASE-CASE ANALYSIS: Prevention of VAP led to mean total costs of 16,119 dollars and 18,268 dollars for patients without preventive measures administered. Thus, costs were saved and instances of VAP were prevented. Similar results were observed in terms of overall survival. RESULTS OF SENSITIVITY ANALYSIS: Prevention of VAP remains cost-saving if the relative risk for VAP because of intervention is <0.923, the costs of the intervention are less than 2,500 dollars, and the prevalence of VAP without intervention is >4%. Bootstrapping confirmed that, with about 80% certainty, oropharyngeal decontamination results in prevention of VAP and simultaneously saves costs. In terms of a survival benefit, the results are less evident; the results indicate that with only about 60% certainty can we confirm that oropharyngeal decontamination would result in a survival benefit and simultaneously save costs. CONCLUSIONS: This study provides strong evidence that prevention of VAP by means of oropharyngeal decontamination is cost-effective.     

Nosocomial viral ventilator-associated pneumonia in the intensive care unit: a prospective cohort study

Objective To determine the incidence, risk factors, and clinical relevance of viral ventilator-associated pneumonia (VAP) in an adult intensive care unit (ICU).Design Prospective observational study.Setting A 22-bed adult medical ICU in a university hospital.Patients All consecutive adult patients ventilated more than 48 h in a 9-month period including regular seasonal viral infections.Interventions A tracheobronchial aspirate upon enrollment and at the time of VAP suspicion.Measurements and results All respiratory specimens were tested in culture, indirect immunofluorescence assay, and PCR or RT-PCR for virological assessment. Patients were followed until ICU discharge or death. One hundred thirty-nine patients were included. Upon enrollment, a respiratory virus was detected in the tracheobronchial aspirate in 25% of patients (35 of 139). The incidence of VAP, defined according to clinical daily evaluation, was 28% (39 of 139 patients). A bacteria was documented in 74% of cases, whereas no case of a causative viral infection was encountered among VAP patients; however, herpes simplex virus type-1 (HSV 1) infection was detected in respiratory specimens of 31% of VAP (12 of 39).Conclusions We found a high incidence of HSV-1 infection in VAP patients; however, nosocomial viral VAP is likely to be rare in ICU, as assessed by the absence of respiratory virus-induced VAP identified in this prospective cohort study.     

Comparison of ventilator-associated pneumonia (VAP) rates between different ICUs: Implications of a zero VAP rate

Objective

Ventilator-associated pneumonia (VAP) is associated with significant morbidity and mortality. Measures to reduce the incidence of VAP have resulted in institutions reporting a zero or near-zero VAP rates. The implications of zero VAP rates are unclear. This study was done to compare outcomes between two intensive care units (ICU) with one of them reporting a zero VAP rate.

Design, Setting and Patients

This study retrospectively compared VAP rates between two ICUs: Utah Valley Regional Medical Center (UVRMC) with 25 ICU beds and American Fork Hospital (AFH) with 9 ICU beds. Both facilities are under the same management and attended by a single group of intensivists. Both ICUs have similar nursing and respiratory staffing patterns. Both ICUs use the same intensive care program for reduction of VAP rates. ICU outcomes between AFH (reporting zero VAP rate) and UVRMC (VAP rate of 2.41/1000 ventilator days) were compared for the years 2007-2008.

Measurements and Main Results

UVRMC VAP rates during 2007 and 2008 were 2.31/1000 ventilator days and 2.5/1000 ventilator days respectively compared to a zero VAP rate at AFH. The total days of ventilation, mean days of ventilation per patient and mean duration of ICU stay per patient was higher in the UVRMC group as compared to AFH ICU group. There was no significant difference in mean age and APACHE II score between ICU patients at UVRMC and AFH. There was no statistical difference in rates of VAP and mortality between UVRMC and AFH.

Conclusions

During comparisons of VAP rate between institutions, a zero VAP rate needs to be considered in the context of overall ventilator days, mean durations of ventilator stay and ICU mortality.     

The epidemiology of intensive care unit-acquired hyponatraemia and hypernatraemia in medical-surgical intensive care units

Introduction

Although sodium disturbances are common in hospitalised patients, few studies have specifically investigated the epidemiology of sodium disturbances in the intensive care unit (ICU). The objectives of this study were to describe the incidence of ICU-acquired hyponatraemia and hypernatraemia and assess their effects on outcome in the ICU.

Methods

We identified 8142 consecutive adults (18 years of age or older) admitted to three medical-surgical ICUs between 1 January 2000 and 31 December 2006 who were documented to have normal serum sodium levels (133 to 145 mmol/L) during the first day of ICU admission. ICU acquired hyponatraemia and hypernatraemia were respectively defined as a change in serum sodium concentration to below 133 mmol/L or above 145 mmol/L following day one in the ICU.

Results

A first episode of ICU-acquired hyponatraemia developed in 917 (11%) patients and hypernatraemia in 2157 (26%) patients with an incidence density of 3.1 and 7.4 per 100 days of ICU admission, respectively, during 29,142 ICU admission days. The incidence of both ICU-acquired hyponatraemia (age, admission diagnosis, Acute Physiology and Chronic Health Evaluation (APACHE) II score, length of ICU stay, level of consciousness, serum glucose level, body temperature, serum potassium level) and ICU-acquired hypernatraemia (baseline creatinine, APACHE II score, mechanical ventilation, length of ICU stay, body temperature, serum potassium level, level of care) varied according to patients' characteristics. Compared with patients with normal serum sodium levels, hospital mortality was increased in patients with ICU-acquired hyponatraemia (16% versus 28%, p < 0.001) and ICU-acquired hypernatraemia (16% versus 34%, p < 0.001).

Conclusions

ICU-acquired hyponatraemia and hypernatraemia are common in critically ill patients and are associated with increased risk of hospital mortality.     

Outcome of early intensive care unit patients readmitted in the same hospitalization

Purpose

The aim of the study was to evaluate factors associated with early readmission to the intensive care unit (ICU) during the same hospitalization and factors associated with adverse outcomes.

Patients and Methods

Among 25 717 admissions, 378 (1.5%) patients were quickly readmitted within 3 days; of these, 374 patients for whom complete medical records were available for review were included. This was a prospective observational study for a 2-year period, with an additional 1-year follow-up.

Results

Respiratory (118 [31.6%]) and cardiovascular (91 [24.3%]) causes accounted for most readmissions. Need for mechanical ventilation during the second ICU stay was the variable most significantly associated with increased mortality (P < .001). Comparing the 2 study periods, we observed a decreased mortality rate (31.3 vs 19.5%; P = .018).

Conclusion

Patients with respiratory and cardiovascular diseases are at greatest risk for early ICU readmission. Better patient assessment and knowledge of factors associated with early readmission may contribute to reduced mortality.     

Selective decontamination of the digestive tract improves survival in patients receiving differential lung ventilation

In a review of the literature on differential lung ventilation (DLV) the average mortality was found to be 47%. The major cause of death (66%) was infection. The effect of a novel infection prevention regimen on the colonisation and infection rate of the respiratory tract and on outcome was studied in polytrauma patients. Nineteen patients who presented with asymmetric pulmonary contusion were treated with DLV (103±72 h) and conventional mechanical ventilation (CMV) (16±10 days). They were treated with selective decontamination of the digestive tract with topical non-absorbable antibiotics in combination with systemic antibiotic prophylaxis starting immediately after admission. In one patient colonisation of the respiratory tract was found with Staphylococcus aureus. This disappeared after continued systemic antibiotic prophylaxis. Colonisation with hospital-acquired Gram-negative bacteria or yeasts was not observed. No patient developed pneumonia throughout the period on conventional mechanical ventilation or on DLV. One patient died from cerebral injury. It is concluded that prolonged endobronchial intubation for DLV can be used without increased risk for pneumonia with this antibiotic regimen and that the very low mortality in this study may be attributed to the prevention of infectious complications.     

Admission high serum sodium is not associated with increased intensive care unit mortality risk in respiratory patients

Background

Because increased serum osmolarity may be lung protective, we hypothesized that increased mortality associated with increased serum sodium would be ameliorated in critically ill patients with an acute respiratory diagnosis.

Methods

Data collected within the first 24 hours of intensive care unit (ICU) admission were accessed using ANZICS CORE database. From January 2000 to December 2010, 436 209 patients were assessed. Predefined subgroups including patients with acute respiratory diagnoses were examined. The effect of serum sodium on ICU mortality was assessed with analysis adjusted for illness severity and year of admission. Results are presented as odds ratio (95% confidence interval) referenced against a serum sodium range of 135 to 144.9 mmol/L.

Results

Overall ICU mortality was increased at each extreme of dysnatremia (U-shaped relationship). A similar trend was found in various subgroups, with the exception of patients with respiratory diagnoses where ICU mortality was not influenced by high serum sodium (odds ratio, 1.3 [0.7-1.2]) and was different from other patient groups (P < .01). Any adverse associations with hypernatremia in respiratory patients were confined to those with arterial pressure of oxygen (PaO₂)/fraction of inspired oxygen (Fio₂) ratios of greater than 200.

Conclusion

High admission serum sodium is associated with increased odds for ICU death, except in respiratory patients.     

Imipenem-resistant Pseudomonas aeruginosa infection at a medical-surgical intensive care unit: Risk factors and mortality

Objectives

The aim of this study was to evaluate the risk factors and attributable mortality associated with imipenem-resistant Pseudomonas aeruginosa (IRPA) infections in a medical-surgical intensive care unit (ICU).

Methods

A retrospective case-control study was carried out at a 16-bed medical-surgical ICU in a 780-bed, university-affiliated hospital. All patients admitted from January 1, 2003, to December 31, 2004, who had nosocomial infection caused by IRPA, were included in the study.

Results

Imipenem-resistant P. aeruginosa was recovered from 63 patients during the study period. One hundred eighty-two controls were matched with cases by period of admission, age, and time at risk. Urinary tract (34.9%) and respiratory tract (22.2%) were the main sources of IRPA isolation. In multivariate analysis, a previous stay in the ICU (odds ratio, 3.54; 95% confidence interval [CI], 1.29-9.73; P = .03) was the only independent risk factor for IRPA infection. The in-hospital mortality rate among case patients was 49% (31 of 63) compared with 33% (61 of 182) for control patients (odds ratio, 1.92; 95% CI, 1.07-3.44; P = .02). Thus, we had an attributable mortality of 16% (95% CI, 9.74%-22.3%; P = .03).

Conclusions

Our study suggests that IRPA infections are strongly related to previous ICU stay, and that IRPA infections significantly increase mortality in those critical patients.