What is nosocomial infection

Nosocomial infection also called hospital acquired infection. Nosocomial infection is defined as an infection occurring in a patient admitted to the health-care settings for more than 48 but without any evidence that the infection was present or incubating at the time of admission ¹. Nosocomial infection includes all infections acquired in the hospital but appearing after discharge usually after 48 hours of discharge. Nosocomial infection is an infection acquired in hospital by a patient who was admitted for a reason other than that infection. Nosocomial infections can also appear within 30 days of post-operative procedure, or within 90 days if there is an implant in place ².

Patients at higher risk for nosocomial infection and mortality frequently experience an immunosuppressed state characterized by defects in immune tolerance, exhaustion, and apoptosis ³.

In the hospitals or other health care facilities, nosocomial infection is a leading cause of increased morbidity, mortality and financial burden ⁴. The incidence of nosocomial infection as most studies reporting data ranged from 3.6 to 12% in high-income countries ⁵ and 5.7 to 19.1% in low- and middle-income coutries ⁶. Predisposing factors, i.e., the invasive procedures ⁷, long hospital stay ⁸, excessive antibiotics usage ⁵ and the existence of severe illness ⁹ lead to nosocomial infection rate in patients admitted to the intensive care unit (ICU) several fold higher than that in the general hospital population ¹⁰. Now, nosocomial infection is more concerned as the focus of safety and quality improvements efforts in many hospitals.

Historically, Staphylococcus, Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli (E. coli) have been the nosocomial infection triad; nosocomial pneumonia, surgical wound infections, and vascular access-related bacteremia have caused the most illness and death in hospitalized patients; and intensive care units have been the epicenters of antibiotic resistance ¹¹.

Nosocomial infection was associated with increased hospital length of stay in both studies, but the effect on mortality varied between 15 and 21% ³. The adjusted absolute increase in mortality specifically attributable to nosocomial infection (population attributable mortality fraction) was only 2% ¹². These data suggest that a significant portion of the difference in mortality after sepsis is actually due to competing factors such as higher admission illness severity rather than nosocomial infection. Other studies have made similar observations linking illness severity to outcome, rather than nosocomial infection ¹³. Furthermore, critically ill patients without sepsis had similarly high rates of nosocomial infection suggesting that ICU exposure, rather than sepsis itself, contributes largely to the development of nosocomial infections. However, infections in patients with sepsis were more commonly due to opportunistic pathogens (enterococci, Pseudomonas aeruginosa and viruses) implying there still may be a link to sepsis-related immunosuppression.

Both exposures and host susceptibility play a role in development of nosocomial infection. As such, differences among studies in nosocomial infection and mortality rates are likely due to differences in patient selection, ICU type, primary type of sepsis, infectious diagnostics/definitions, infection prevention practices, and geographical location. Regardless of their impact on mortality, nosocomial infections are common and remain a significant factor in morbidity during recovery from sepsis. In addition, they are a burden on the health care system and account for an additional $20,000–40,000 dollars per episode ¹⁴. Whether immunostimulatory therapies will reduce rates of secondary infection in patients with sepsis will be determined in ongoing clinical trials.

Nosocomial pathogens

Typical nosocomial pathogens ¹²:

Gram positive (45.2%)

• Staphylococcus epidermidis (14.7%)
• Enterococcus faecalis (12.0%)
• Enterococcus faecium (6.3%)
• Staphylococcus aureus (6.0%)
• Others (6.2%)

Gram negative (26.6%)

• Pseudomonas aeruginosa (9.0%)
• Escherichia coli (3.9%)
• Klebsiella pneumonia (2.7%)
• Stenotrophomonas maltophilia (2.7%)
• Others (8.3%)

Fungi (9.6%)

• Candida albicans (2.7%)
• Candida glabrata (1.2%)
• Others (5.7%)

Viruses (9.9%)

• Herpes simplex (3.9%)
• Cytomegalovirus (2.1%)
• Others (3.9%)

Most common nosocomial infection

One large retrospective study estimated that 1 in 3 patients with sepsis will develop a nosocomial infection and half of these infections will occur in the lung ¹⁵. A larger prospective study found that 1 in 8 patients will develop nosocomial infection and one-quarter of these will be pulmonary infections ¹⁶. In both studies, nosocomial infection developed in the late phase of sepsis at a median of 9 days from admission. In the study by Zhao and colleagues ¹⁵, the most common site of secondary infection was pulmonary (52.5%) and there was no association between primary site of infection (e.g., pulmonary, abdominal, skin/soft tissue, urinary) and the development of secondary infection. In the study of van Vught and colleagues ¹⁶, the most common site of secondary infection was cardiovascular (35.3%). The distribution of primary and secondary infection sites in both studies were distinct, suggesting that secondary infection resulted from a new infectious insult rather than inadequately managed primary infection. Patient risk factors for development of nosocomial infection were similar and included older age, higher illness severity score, longer intensive care unit (ICU) length of stay and respiratory insufficiency. ICU-specific exposures such as central venous catheterization and endotracheal intubation also increased risk. The most common causative pathogens were bacterial in both studies.

Table 1. Primary and secondary sites of infection and cause of secondary nosocomial infection in patients presenting with sepsis.

Infection site	Primary	Secondary
Pulmonary	48%	25.4%
Cardiovascular*	7.3%	35.3%
Abdominal	19%	15.9%
Neurological	2.2%	12.7%
Skin/Soft tissue	2.2%	3.9%
Urinary	4.3%	1.2%
Other¥	16.8%	19%

Footnotes:

* Cardiovascular site of infection included bacteremia and catheter-related bloodstream infections

¥ Other sites of infection included lung abscess, sinusitis, pharyngitis, tracheobronchitis, endocarditis, mediastinitis, myocarditis, postoperative wound infection, bone and joint infection, oral infection, eye infection, reproductive tract infection.

[Source ¹² ]

Nosocomial pneumonia

Nosocomial pneumonia also called hospital-acquired pneumonia (HAP), is defined as pneumonia that occurs 48 hours or more after hospital admission and not incubating at the admission time ¹⁷. Ventilator-associated pneumonia represents a significant sub-set of nosocomial pneumonia occurring in intensive care units (ICUs) and is defined as pneumonia that occurs more than 48 to 72 hours after tracheal intubation and is thought to affect 10% to 20% patients receiving mechanical ventilation for more than 48 hours ¹⁸.

Common pathogens of nosocomial pneumonia and ventilator-associated pneumonia include aerobic gram-negative bacilli (e.g. Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Enterobacter spp, Acinetobacter spp) and gram-positive cocci (e.g., Staphylococcus aureus, which includes methicillin-resistant Staphylococcus aureus, Streptococcus spp). Differences in host factors and in the hospital flora of an institution affect the patterns of the causative pathogens ¹⁹.

Nosocomial pneumonia occurs at a rate of 5 to 10 per 1000 hospital admissions and is considered the most common cause of hospital-acquired infection in Europe and the United States ¹⁷. Over 90% of pneumonia episodes developing in ICUs occur in patients who are intubated and mechanically ventilated ²⁰.

Risk factors for nosocomial pneumonia

Risk factors for multidrug-resistant ventilator-associated pneumonia

• Septic shock at the time of ventilator-associated pneumonia
• Acute respiratory distress syndrome (ARDS) before ventilator-associated pneumonia onset
• Intravenous antibiotic use within 90 days of ventilator-associated pneumonia
• Hospitalization more than 5 days of before the occurrence of ventilator-associated pneumonia
• Acute renal replacement therapy before ventilator-associated pneumonia onset

Risk factors for multidrug-resistant nosocomial pneumonia

• Intravenous antibiotic use within 90 days of nosocomial pneumonia

Risk factors for methicillin-resistant staphylococcus aureus (MRSA) ventilator-associated pneumonia/nosocomial pneumonia

• Intravenous antibiotic use within 90 days of nosocomial pneumonia or ventilator-associated pneumonia

Risk factors for multidrug-resistant pseudomonas ventilator-associated pneumonia/nosocomial pneumonia

• Intravenous antibiotic use within 90 days of nosocomial pneumonia or ventilator-associated pneumonia ¹⁸.

Nosocomial pneumonia symptoms

Nosocomial pneumonia symptoms may include cough, expectoration, a rise in body temperature, chest pain or dyspnea. Signs include fever, tachypnea, consolidations or crackles.

Nosocomial pneumonia diagnosis

Establishing the diagnosis of nosocomial pneumonia remains controversial and there is no superior method. In the guidelines for the management of nosocomial pneumonia and ventilator-associated pneumonia by Infectious Diseases Society of America/American Thoracic Society 2016, diagnosis is based upon a presence of new lung infiltrate and clinical evidence that the infiltrate is of an infectious cause (new onset of fever, purulent sputum, leukocytosis, and a decline in oxygenation). Clinical pulmonary infection score (CPIS), which includes clinical and radiological criteria, is suggested to increase the likelihood of the presence of pneumonia, but some investigators suggest that the CPIS while being sensitive, lacks specificity and leads to unnecessary antimicrobial treatment ²¹.

Bacteriologic evaluation

For patients with ventilator-associated pneumonia sampling the lower airways to get quantitative cultures can be done by:

• Blind tracheobronchial aspiration (TBAS), which is a noninvasive technique done by inserting a flexible catheter into the distal trachea via the endotracheal tube. This technique is relatively noninvasive. However, this blind technique prevents direct sampling of the lung segments which have an infiltrate on the radiograph, and this may lead to increasing the false-negative rate. Also, contamination of the suction catheter as it traverses the endotracheal tube and more proximal airways may increase the false-positive rate.
• Bronchoscopy with bronchoalveolar lavage (BAL) allows the sampling of the lung segments which are suspected to be affected by pneumonia decreasing the false-negative rate. But, the technique is operator dependent, and contamination of the bronchoscope can affect the results. Also, bronchoscopy can worsen hypoxemia that may not be tolerated by some patients.
• Protected specimen brush (PSB) which can be advanced through a bronchoscope and has the advantage of avoiding contamination with upper airway secretions, as it is not advanced until positioned in the distal airway ²².

For patients with nosocomial pneumonia (non-ventilator-associated pneumonia), noninvasive methods for sampling the lower airways include spontaneous expectoration, sputum induction, nasotracheal suctioning in a patient who cannot cooperate to produce a sputum sample.

All respiratory tract samples should be sent for microscopic analysis and culture.

Microscopic analysis

The microscopic analysis includes the analysis of polymorphonuclear leukocytes and a gram stain. The microscopy can be helpful in determining a possible pathogen and the antibiotic selection until the results of the culture are available. The presence of abundant neutrophils and the bacterial morphology may suggest a likely pathogen.

Quantitative cultures

Diagnostic thresholds include:

• Endotracheal aspirates 1,000,000 colony forming units (CFU)/mL
• Bronchoscopic- or mini-bronchoalveolar lavage 10,000 CFU/mL
• Protected specimen brush 1000 CFU/mL ²²

New molecular diagnostic tests

New molecular diagnostic tests like multiplex polymerase chain reaction assay, which detects an array of respiratory bacterial pathogens and many antibiotic resistance genes, offer the advantage of rapid identification of pathogens and resistance patterns for rapid choosing the antibiotic regimens ²³.

Nosocomial pneumonia treatment

Initial empiric therapy for nosocomial pneumonia and ventilator-associated pneumonia should include agents active against Staphylococcus aureus, Pseudomonas aeruginosa, and other gram-negative bacilli. The choice of antibiotics for empiric therapy should be based on the common pathogens and susceptibility patterns within the health care facilities and also based on the patient’s risk factors for multidrug resistance ²⁴.

• For patients with nosocomial pneumonia who have a risk factor for MRSA infection, specificall those with prior intravenous antibiotic use within 90 days, hospitalization in a unit where greater than 20% of S. aureus isolates are methicillin resistant, or the prevalence of MRSA is not known, or who are at high risk for mortality, prescribe an antibiotic active against MRSA like vancomycin or linezolid is recommended (weak recommendation, very low-quality evidence). Risk factors for mortality include the need for ventilator support due to nosocomial pneumonia and septic shock.
• For patients with nosocomial pneumonia with no risk factors for MRSA infection and not at high risk of mortality, prescribe an antibiotic with activity against MSSA like piperacillin-tazobactam, cefepime, levofloxacin, imipenem, or meropenem.
• For patients with nosocomial pneumonia who have factors for Pseudomonas or other gram-negative infection or high risk for mortality, prescribe antibiotics from 2 different classes with activity against P. aeruginosa (weak recommendation, very low-quality evidence). Other patients with nosocomial pneumonia may be prescribed a single antibiotic active against P. aeruginosa like piperacillin-tazobactam, cefepime, and ceftazidime, levofloxacin, ciprofloxacin, imipenem, meropenem, amikacin, gentamicin, and aztreonam ¹⁹.

Continuation therapy

All patients with nosocomial pneumonia or ventilator-associated pneumonia should be reevaluated for clinical response and the microbiologic results after initial empiric antimicrobial therapy.

• For patients in whom the causative organism has been identified, the empiric regimen should be narrowed according to the pathogen’s susceptibility.
• For patients who are clinically improving and who do not have an identified pathogen, empiric treatment for S. aureus or multidrug-resistant, gram-negative bacilli can be stopped if these organisms have not detected in culture from a high-quality specimen within 48 to 72 hours.
• Patients who have not improved within 72 hours of starting empiric antibiotics should be evaluated for complications, other sites of infection, and alternate diagnoses. If the diagnosis of pneumonia appears certain, and the patient has risk factors for drug-resistant pathogens additional pulmonary cultures should be done, and the empiric regimen should be expanded to cover additional resistant organisms ¹⁹.

Duration of antibiotic therapy in most patients with nosocomial pneumonia or ventilator-associated pneumonia of 7 days appears to be as effective as longer durations and may limit the emergence of a resistant organisms. However, for patients with a severe illness, bacteremia, slow response to therapy, immunocompromise, and complications such as empyema or lung abscess, a longer duration of therapy is indicated ¹⁹.

Nosocomial pneumonia prognosis

Many studies have found that nosocomial pneumonia is associated with an increased risk of death. The all-cause mortality associated with ventilator-associated pneumonia ranges from 20% to 50% in different studies. Variables associated with increased mortality include:

• Severity of illness at the time of diagnosis (e.g., shock, coma, respiratory failure, acute respiratory distress syndrome)
• Bacteremia
• The underlying co-morbidities ²⁵

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