Hospital-acquired Respiratory-Tract Infections in the Teaching Hospitals of Sfax

Hospital-acquired Respiratory-Tract Infections (HARTIs) are identified as the most frequent type of hospital-acquired infections. They can engender significant morbidity and mortality rates, generating a heavy economic burden, especially in the limited resources countries. In this perspective, this study aimed to determine the prevalence of HARTIs in the University Hospitals (UHs) of Southern Tunisia and to identify their main associated factors. It was a cross-sectional study conducted in the two UHs of Sfax governorate, Tunisia, from July 10 to 24th, 2017, including all hospitalized patients for at least 48 hours. It was a 1-day pass per department and a 1-week survey per UH. In total, 34 cases of HARTIs were notified among 752 surveyed patients, accounting for an overall prevalence of 4.5%. The prevalence of HARTIs in the Intensive Care Units (ICU) was 20.6%. Multivariate logistic regression analysis showed that developing a HARTI in non-ICU was independently associated with tobacco use [Adjusted Odds Ratio (AOR) = 2.83; 95% Confidence Interval (95% CI) = [1.10–7.27]; p = 0.03], central vascular catheter (AOR = 5.70; 95% CI = [1.29–25.15]; p = 0.022) and McCabe Index ≥1 (AOR = 7.38; 95% CI = [2.73–19.97]; p < 0.001). In ICU, only endotracheal tube was independently associated with HARTIs (AOR = 42.5; 95% CI = [4.97–64.13]; p = 0.001). This study illustrated the extent of HARTIs problem threatening the quality of care in Southern Tunisia. Identifying the risk factors of HARTIs in both ICUs and non-ICUs may help healthcare workers to ascertain the avoidability of these infections.


INTRODUCTION
Hospital-acquired Infections (HAIs) represent a major public health problem.According to the latest estimates from the World Health Organization, 7% of hospitalized patients in developed countries would acquire at least one HAI, whereas in developing countries, 10% of these patients would develop a HAI [1].Hospital-acquired Respiratory Tract Infections (HARTIs) have been identified as the most frequent type of HAIs [2,3].They include upper respiratory tract infections, pneumonia, and other lower respiratory tract infections such as bronchitis and tracheobronchitis [4].Hospitalacquired Pneumonia (HAP) may be managed both in a medical ward and in an Intensive Care Unit (ICU), when the prognosis is more severe.As a subset of HAP, Ventilator-associated Pneumonia (VAP) is considered one of the most frequent infections in ICU patients [5].HAP and VAP may engender significant morbidity and mortality rates, prolong the hospital Length of Stay (LOS), and necessitate additional diagnostic and therapeutic interventions, generating a heavy economic burden, especially in countries with limited resources [6].The presence of specific hosts such as male sex, pre-existing pulmonary disease, and multiple organ system failure added to several invasive devices could enhance patients' susceptibility to develop HARTIs [7,8].Thorough knowledge and identification of the factors associated with these infections are recognized as a key step to develop infection control programs and design treatment protocols.However, in developing countries, the awareness gap of these risk factors and the lack of reliable data make it difficult to estimate the extent of this public health problem [9].In Tunisia, according to the first national survey conducted in 2005, HARTIs were the second most frequent type of HAIs, with a prevalence of 2.6% [10].The two University Hospitals (UHs) of Sfax governorate, which are the most qualified hospitals for healthcare management in Southern Tunisia, received numerous patients from neighboring governorates.With this perspective, this study aimed to determine the prevalence of HARTIs in the UHs of Sfax and to identify the main associated factors.
UH.The latter is divided into adult and pediatric departments, whereas HBUH has surgery and general medicine departments (neurology, oncology, and radiotherapy) as well as ICUs.

Study Population and Case Definition
The same protocol of the national Tunisian survey of HAI conducted in 2005 and 2012 was applied in this survey [4].Eligible patients were all inpatients admitted on the survey day for at least 48 hours.We excluded all patients hospitalized less than 48 hours or undergoing a same-day treatment or surgery, as well as departments of emergencies, hemodialysis, radiology and outpatient departments.

HARTI Definitions
All types of HARTIs were defined according to United States Centers of Disease Control and Prevention (CDC) criteria [11].HARTIs were classified as upper respiratory tract infections (HAURTIs), including angina, pharyngitis, laryngitis, sinusitis, otitis media and flu, and lower respiratory tract infections (HALRTIs) which include bronchitis, tracheobronchitis, bronchiolitis, tracheitis, lung abscess, and empyema [4].An infection was considered hospital-acquired unless it was present or incubating at the time of admission.We recorded only active HARTIs including those which were symptomatic or under anti-infective treatment on the day of the survey.HAP was defined as new or increased production of purulent sputum and/or fever >38°C with appropriate chest signs and/or new or progressive radiographic evidence of chest infiltrates not attributed to embolus or heart failure [12].The remaining cases were classified as bronchitis.All HALRTIs in patients who were mechanically ventilated were considered to be VAP [12].

Data Collection
A pilot study was undertaken prior to the survey, in June 2017, to examine the feasibility of the approach.Standard information was collected by epidemiologists and hygiene practitioners trained for this purpose using anonymous questionnaires.They collected data at bedside by interrogating and examining patients as well as consulting medical and nursing chart, microbiology reports, X-ray and temperature charts.Infections were also identified by consultation with the clinical team in charge of patient care.In fact, the diagnosis of HARTI was first suspected by the investigators and then confirmed by medical staff including expert doctors and hygiene referents in each department, who verified the diagnosis criteria for each patient.In a few cases, a follow-up of 2 or 3 days was required to have the results of complementary examinations done during the survey day and then to probably confirm (or disprove) the HARTI.For each patient, variables related to sociodemographic and clinical profile, exposure to indwelling invasive devices or a surgical procedure and anti-infective treatment prescribed on the day of the survey were recorded.Patients were classified according to the severity of their underlying condition as proposed by McCabe and Jackson (0 = non-fatal disease; 1 = ultimately fatal dis ease; 2 = rapidly fatal disease) [13].Other details dealing with organisms isolated in respiratory sputum were also collected.

Statistical Analysis
Statistical analyses were performed using SPSS version 20 (SPSS Inc., Chicago, IL, USA).Categorical variables were presented as percentages.The Kolmogorov-Smirnov test was used to assess the distribution of continuous variables.The results of continuous variables were presented as medians and Interquartile Ranges (IQR) when they were not normally distributed.Factors statistically associated with HARTIs were determined using univariate logistic regression analysis [Crude Odds Ratio (COR); 95% confidence interval (95% CI)].To define the independent risk factors predictive of HARTIs in both ICU and non-ICU, two multivariate analysis models were carried out using logistic regression [Adjusted Odds Ratio (AOR); 95% CI; p].All variables that had p value ≤0.2 at the logistic univariate analysis were included in the logistic regression model, and a backward stepwise approach was used.Any variable with a p < 0.05 was retained in the final model.

HARTIs Types and Their Distribution
According to Specialties HALRTIs represented 85.3% (29 cases) of all HARTIs, among which 86.2% had HAP (25 cases).The prevalence of HAP was 3.3%.Thirteen of the 25 patients with HAP (52%) had VAP.All cases with VAP were observed in the ICU.The highest prevalence of HARTIs was in ICUs (20.6%)Table 2.

DISCUSSION
Hospital-acquired respiratory tract infections are a serious patient safety issue in UHs worldwide.Thus, the prevention of these  infections has become a priority, whose essential component is establishing epidemiological surveillance systems of HARTIs in these hospitals.Otherwise, reliability of data is a challenge in developing countries.Prevalence surveys have proved their usefulness thanks to their lower cost and rapidity of execution.This survey is the first study to assess the burden of HARTIs in the local area.The overall prevalence of HARTIs in our UHs was relatively high (4.5%).Although prevalence studies have limitations in comparison, our result was similar to that of the UH of Center-East of Tunisia [14] and higher than the prevalence of HARTIs reported at the Tunisian national level in 2005 (2.05%) [4].Prevalence rates were even lower in France (1.4%) [15] and China (1.8%) [3].The reasons for differences observed in prevalence rates could be attributed to the differences in the diagnostic techniques used and the lack of standardized prevention methodology worldwide.Furthermore, the low sensitivity of radiological and clinical findings could result in a low degree of certainty in the diagnosis of HALRTIs and then the estimation of their real prevalence rate.
The study results demonstrated that HARTIs mainly occurred in the lower respiratory tract and the prevalence of HALRTIs was 3.8%.This rate was higher than that reported in a point prevalence survey conducted in France (1.2%) [15], Europe (2%) [16], and Greece (2.5%) [12].The majority of HALRTIs were HAP, with a prevalence of 3.3%.Previous studies conducted in both developed (1.3%) [2,15] and developing countries (1.1%) [17,18] showed lower prevalence rates.Possible explanations for these disparities may be differences in criteria used for HAP diagnosis, data collection procedures, as well as the vocation and the size of the studied UHs.In fact, rates comparison could only be worthwhile if similar methodologies have been adopted [19].Moreover, the increased susceptibility of our population to HALRTIs and precisely to HAP might be explained by the absence of an effective strategy of infection control in Southern Tunisia.Consequently, there is a lack of unified hygiene policies and awareness of healthcare workers toward preventive measures for HAP.Thus, healthcare providers would have poor compliance with HALRTI control practices including regular oral care, preventing cross-contamination or colonization via hands of personnel, appropriate disinfection or sterilization of respiratory-therapy devices and use of available vaccines to protect against particular infections.Other new measures are being investigated and involve reducing oropharyngeal and gastric colonization by pathogenic microorganisms [20].
The greatest prevalence of HARTIs was recorded in ICUs and all patients with HARTIs in ICUs had VAP.The reasons for this could be attributed to the alteration of the patients' natural barriers owing to the underlying illness severity, the virulence of infectious agents in ICUs and their antimicrobial resistance, as well as the use of advanced invasive medical procedures such as endotracheal tube.In fact, creating an artificial respiratory tract deprives a patient of the possibility to heat, humidify, and purify inhaled air [7].This, in turn, generates a series of nursing and medical interventions that may be conducive to developing HAP, a particular type of which is VAP [7].
Gram-negative bacilli represented the majority of all recovered microorganisms, among which Acinetobacter bau mannii was the most frequently isolated.These results were consistent with other studies conducted in Greece [12] and Cuba [21].In fact, Acinetobacter bau mannii is mainly encountered in hospital environments where it can survive for long periods owing mainly to its capacity to withstand desiccation.All these characteristics could increase the spread of epidemic strains especially through breathing machines or others equipment if they were not properly cleaned, and also through the hands of healthcare workers when appropriate control measures were not taken [21].Thus, inadequate cleaning and hygiene, environmental disinfection, poor adherence to hand hygiene or a general breakdown of hospital infection control protocols would lead to increasing rates of Acinetobacter bau mannii infection.These results suggest the need for thorough investigation of quality control systems to assess compliance with infection control norms in these UHs.
Tobacco use increased the risk of HARTIs in non-ICUs.In fact, it was well documented that there is an increased susceptibility to respiratory tract infections in smokers compared with non-smokers [22].
The mechanisms causing the enhanced vulnerability to respiratory infections in smokers include disruptive effects on the immune system such us alterations in the innate and adaptive immune responses, and modifications in the respiratory microbiota with fewer normal bacteria and more potential pathogens [22].Moreover, the McCabe index as well as the presence of central vascular catheter were significantly associated with the occurrence of HARTIs in the study population.Thus, the prevalence of HARTIs might be decreased by the judicious use of indwelling catheters and the strict adherence to CDC recommendations.Actually, the rational use of catheter and the reduction of its duration have been reported as a major factor in preventing HAIs.However, for most intensivists, it would be quite difficult to reduce it.Thus, respecting hygiene precautions and using aseptic techniques while handling these devices for fragile patients are highly recommended.
In the ICUs, endotracheal tube was an independent risk factor of HAP, as described in several studies [23][24][25].In fact, owing to differences in inspired gas and ambient air temperatures, a condensate will be formed in the tubing used in mechanical ventilation, which could lead to several problems [23].Indeed, this condensate could easily become contaminated.Furthermore, using an artificial airway could foster micro-aspirations by impairing effective removal of secretions from the respiratory tract to the outside.To mitigate the risk of inhalation of contaminated condensate, it is recommended to use in-line devices with one-way valves and to reduce the number of ventilation days or to resort to non-invasive ventilation [26].

LIMITATIONS
Although a standardized measurement approach was adopted and investigators were trained on collecting data, random measurement errors could arise from human investigators and the variance of clinical opinion among experts when diagnosing HARTIs.Furthermore, in the UHs of Sfax there was a lack of knowledge in some clinicians regarding infection control policies, especially for those who have a heavy workload, which can affect the care quality.

CONCLUSION
In conclusion, this study illustrated the extent of HARTIs problem threatening the quality of care in our region.The highest prevalence of these infections was noted in ICUs.Invasive respiratory devices were found to be the main risk factors.Thus, to reduce the burden of VAP, it is recommended to promote procedures that safely reduce duration of intubation whenever possible, to consider noninvasive ventilation, and to start an early and appropriate weaning protocol.Moreover, knowledge of the prevalent organisms helps to rationalize the use of antimicrobial agents.These findings pointed to an urgent need to manage the spread of these infections by implementing meticulous preventive measures in high-risk groups with adequate staffing and strict hospital infection control policy.

Table 1 |
Sociodemographic and clinical characteristics of patients with hospital-acquired respiratory tract infections LOS, length of hospital stay.

Table 3 |
Number and relative share of isolated microorganisms in patients with hospital-acquired respiratory tract infections

Table 4 |
Factors associated with hospital-acquired respiratory tract infections in non-intensive care units: results of univariate and relevant multivariate analysis *Statistically significant difference.AOR, adjusted odds ratio; CI, confidence interval; COR, crude odds ratio; HARTIs, hospital acquired respiratory tract infections; LOS, length of hospital stay.

Table 5 |
Factors associated with hospital-acquired respiratory tract infections in intensive care units: results of univariate and relevant multivariate analysis