Bacterial Resistance and Mortality in an Intensive Care Unit

The goal was to identify risk factors for healthcare–associated infections by resistant microorganisms and patient mortality in an Intensive Care Unit. A prospective and descriptive epidemiological research was conducted from 2005 till 2008, involving 2300 patients. Descriptive statistics, bivariate and multivariate logistic regression analysis were used. In bivariate analysis, infection caused by resistant microorganism was significantly associated to patients with community-acquired infection (p=0.03; OR=1.79) and colonization by resistant microorganism (p<0.01; OR=14.22). In multivariate analysis, clinical severity (p=0.03; OR=0.25) and colonization by resistant microorganism (p<0.01; OR=21.73) were significant. Mortality was associated to the following risk factors: type of patient, average severity index, besides mechanical ventilation. The relation between resistant microorganisms and death shows the need to monitor adherence to infection control measures so as to improve care quality and mainly survival of critical patients.


Introduction
Intensive Care Units (ICUs) deliver care to patients in clinically severe conditions, generally involving extended hospitalization and invasive procedures (central venous catheters, indwelling urinary catheters and mechanical ventilation).Hence, patients admitted to ICUs are more susceptible to the development of healthcare-associated infections (HAI), representing about 25% of all hospital infections, and especially by resistant microorganisms (1) .www.eerp.usp.br/rlaeRev. Latino-Am.Enfermagem 2010 Nov-Dec;18 (6):1152-60.
In the global context, the growing emergence of microorganisms resistant to antimicrobials has been a great source of concern, due to the prolonged hospitalization time, higher treatment cost, the reduced therapeutic arsenal and/or the risk of patient death (2) .
In addition, it is important to highlight that patients undergoing critical care are more predisposed to a range of hospital infections, especially caused by multi-resistant microorganisms, due to the complex nature of care in (MRSA) and Escherichia coli (1)(2)(3)(4)(5) .In Brazil, research at intensive care units report on an association between, on the one hand, use of indwelling urinary catheters, central catheters and mechanical ventilation and, on the other, increased infections developed at these units, a situation in which more than 75% of patients with infections use these procedures.Also, the predominance of resistant agents like Staphylococcus aureus, Pseudomonas aeruginosa and Klebisiella Pneumoniae is observed (6)(7)(8)(9) .
In addition, mortality rates at ICUs is high, ranging from nine to 38%.When patients developed infections caused by resistant microorganisms, this rate can rise up to 70% (3,(10)(11) .Brazilian studies reports similar rates, reaching 50% when associated with infections by resistant microorganisms (8)(9) .
Given the relevance of the theme and the complexity of intensive care patients, this study aimed to identify the factors associated with the risk of developing healthcareassociated infections caused by resistant microorganisms and patient mortality at an ICU of a university hospital.

Methods
A prospective and descriptive epidemiological study was carried out at the adult Intensive Care Unit of a university hospital.
All patients admitted to the ICU, and hospitalized for more than 24 hours between August 2005 and July 2008 were eligible for the study, excluding those patients with incomplete or missing data in the patient chart records related to the research variables.This unit comprises a highly trained multiprofessional team that delivers patient care, approximately 90% originating in the unified health system (SUS) and the remainder in health insurances and private patients.

Definitions
The following definitions were adopted, according to the National Nosocomial Infections Surveillance (NNIS) System: -Community-acquired infections: infections notified upon the patient's admission to the unit, originating in the community, another hospital or other hospitalization units in the study hospital.
-Surgical patients: patients submitted to surgical procedures involving incision and suture, including videolaparoscopic procedures, carried out at the Surgical Center.
To define the bacterial resistance markers adopted

Data collection
For data collection, nursing records and patient charts were used, besides microbiological test results.
The collected data were related to gender, age, origin,

Data analysis
After completing the data collection instrument, the

Resistant microorganisms as causal agents of infection
In Table 2, infections caused by resistant microorganisms are described in relation to the variables selected after they had demonstrated statistical significance in bivariate analysis.In this study, four variables were considered to describe patients' use of invasive procedures: one is "invasive procedures", with the dichotomous response "yes" and "no", to describe the use of mechanical ventilation, indwelling urinary catheter and/or central venous catheter; the others are "mechanical ventilation", "indwelling urinary catheter" and "central venous catheter".Each of these is also dichotomous.
Due to the fact that almost 100% of patients with infections used invasive procedures, the statistical analysis models assessed this variable as a constant.Hence, these procedures were automatically removed from the analysis, as they exerted no significant effect on the response variable.Hence, for statistical analysis purposes, "mechanical ventilation", "indwelling urinary catheter" and "central venous catheter" were considered individually.Assuming that colonization was significant in the presented comparisons between HAI by resistant microorganisms and SM, the fact that determined the development of infections by resistant microorganisms was colonization by these microorganisms.The identified odds ratio, considerably higher than that of other variables in bi and multivariate analysis, reinforces this idea, evidencing its greater role in infection development caused by these microorganisms.study, where a large part of patients were admitted from other hospital sectors (other units and emergency care) and were hospitalized at the ICU for more than four days (14)(15) .

Mortality-associated factors
Besides, the severity of ICU patients makes them more vulnerable to HAI when compared with other units, with five to ten times higher probabilities of catching this kind of infection (16) .
Many factors are related with the risk of catching HAI, such as disease severity, underlying disease, duration of ICU hospitalization and invasive procedures, the latter of which is frequently associated with infection by resistant microorganisms, together with high patient density and this population's susceptibility (10,16) .
In line with this finding, research also related the occurrence of HAI with the use of invasive procedures.
Among these, the use of indwelling urinary catheters stood out, which is also considered a risk factor for HAI development (17)(18) .
Studies appoint that community-acquired infections affect between 13.5 and 61.3% of hospitalized patients.
When caused by Methicillin-resistant Staphylococcus aureus, infection rates increase, including surgical site infection, pneumonias associated with mechanical ventilation and bacteremia (15,(19)(20) .These studies, however, do not directly relate the presence of previous community-acquired infections with the occurrence of infections caused by resistant microorganisms.
Hence, available literature on ICU patients and infections caused by resistant microorganisms does not offer a defined profile yet that permits comparisons with the data found in this study.
Besides, patients with community-acquired bloodstream infections display mortality rates of approximately 40%, against 18% for patients without reports of community-acquired infections (21) .
Patients initially colonized by resistant microorganisms developed infections in 11.1% and 4% of cases, when the causal microorganism was MRSA and VRE, respectively (22)(23) .In the present study, 61.2% of colonized patients developed some kind of infection, but the type of microorganism was not specified.
A consensus exists in literature that bacterial resistance has been an important factor for increased mortality rates, mainly in critically ill patients (24)(25) .
In the assessment of risk factors for ICU mortality, this study identified statistical significance in bivariate analysis for all study variables, except patients' gender and age.In line with this finding, other studies described (4,10,22) lack of significance between gender/age and the development of infections by resistant microorganisms, even mentioning analysis of patients over 75 years of age.
Besides, some studies confirm these findings regarding the significant association between patients who developed infections and/or were submitted to mechanical ventilation, including the occurrence of deaths (4,10,(26)(27)(28)(29) .One of these studies mentions that the chance of death is between two and ten times higher for patients using this device, with death rates that can range between 24 e 76% (27) .According to some of these studies, in patients who received mechanical ventilation, respiratory tract infection with resistant microorganisms is common and associated with higher mortality (28)(29) .
In literature, however, divergence exists on the association between mortality and infection development, even when using multivariate logistic regression (4,10,22) .
On the other hand, infections constitute independent risk factor for mortality and, to the extent that bacterial resistance to antibiotics increases, the possibility of adequate infection treatment decreases, favoring outcomes like death (26) .

Conclusion
The emergence of resistant microorganisms is a source of concern for researchers and professionals intensive care units, multiple interventions and factors related to patients themselves.Data from North American studies indicate that up to 50% of ICU infections are associated with the use of invasive procedures, caused by resistant microorganisms, frequently Acinetobacter sp, methicillin-resistant Pseudomonas sp.Klebsiella sp.Staphylococcus aureus clinical severity index upon admission to the ICU, patient type, time of stay at the unit, community-acquired infection diagnosis, patient colonized with resistant microorganisms during hospitalization, use of invasive procedures, hospital infection and patient outcome.
responsible for healthcare-associated infection, and a priority all over the world.To establish control of these pathogens, getting to know the risk factors for infection development becomes essential, mainly when considering a clientele of critically ill patients.ICU hospitalizations for more than four days, diagnoses of community-acquired infections upon admission to the unit, use of indwelling urinary catheter and colonization by resistant microorganisms appeared as risk factors for the development of infections by resistant microorganisms.The patients' surgical profile and clinical severity upon admission to the ICU, besides the use of mechanical ventilation, appeared as risk factors for death.The detection of risk factors and the possibility of acting on them can enhance the control of bacterial resistance dissemination, entailing greater control of colonization and, consequently, of high infection rates at the ICU.Thus, monitoring patients with communityacquired infections and/or patients colonized by resistant microorganisms is extremely valuable for the early establishment of measures to reduce the possible dissemination of resistant microorganisms.Besides, patients with risk factors deserve special attention during care delivery by the entire health team.

Table 2 -
Estimated Odds Ratios (OR) based on logistic regression analysis, assessing the association between infection by resistant microorganism and different patient characteristics at the Intensive Care Unit.Belo Horizonte,

Table 3 -
Estimated Odds Ratios (OR) based on logistic regression analysis, assessing the association between mortality and different patient characteristics at the Intensive Care Unit.Belo Horizonte, 2009