Nosocomial Pneumonia

Etiology

Common pathogens of HAP and VAP 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 S. aureus, Streptococcus spp). Differences in host factors and in the hospital flora of an institution affect the patterns of the causative pathogens.[2]

Risk Factors for Multidrug-Resistant (MDR) VAP

• Septic shock at the time of VAP
• ARDS before VAP onset
• Intravenous antibiotic use within 90 days of VAP
• Hospitalization more than 5 days before the occurrence of VAP
• Acute renal replacement therapy before VAP onset 

Risk Factors for MDR HAP 

• Intravenous antibiotic use within 90 days of HAP 

Risk Factors for MRSA VAP/HAP 

• Intravenous antibiotic use within 90 days of HAP or VAP 

Risk Factors for MDR Pseudomonas VAP/HAP

• Intravenous antibiotic use within 90 days of HAP or VAP.[1][3][2]

Epidemiology

HAP 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. Over 90% of pneumonia episodes developing in ICUs occur in patients who are intubated and mechanically ventilated.[1][3]

History and Physical

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

Evaluation

Clinical Evaluation

Establishing the diagnosis of HAP remains controversial, and there is no superior method. In the guidelines for the management of HAP and VAP by the Infectious Diseases Society of America/American Thoracic Society 2016, diagnosis is based upon the presence of a 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 [4][5]

Bacteriologic Evaluation

For patients with VAP sampling the lower airways to get quantitative cultures can be done by:

• Blind tracheobronchial aspiration (TBAS) 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 which may not be tolerated by some patients. 
• Protected specimen brush (PSB) 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.[6] 

For patients with HAP (non-VAP), noninvasive methods for sampling the lower airways include spontaneous expectoration, sputum induction, and 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. Microscopy can be helpful in determining a possible pathogen and 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-BAL 10,000 CFU/mL
• PSB 1000 CFU/mL[6][7]

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.[8]

Treatment / Management

Initial empiric therapy for HAP and VAP 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 healthcare facilities and also based on the patient's risk factors for multidrug resistance.[9][2](A1)

• For patients with HAP who have a risk factor for MRSA infection, specifically 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 HAP and septic shock.                                               
• For patients with HAP 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 HAP 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 HAP may be prescribed a single antibiotic active against P. aeruginosa, like piperacillin-tazobactam, cefepime, ceftazidime, levofloxacin, ciprofloxacin, imipenem, meropenem, amikacin, gentamicin, and aztreonam.[2]
(A1)

Continuation Therapy

All patients with HAP or VAP should be reevaluated for clinical response and 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 been 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.[2]
(A1)

Duration of antibiotic therapy in most patients with HAP or VAP of 7 days appears to be as effective as longer durations and may limit the emergence of 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.[2](A1)

Differential Diagnosis

• Acinetobacter

• Adenovirus

• Bacterial sepsis

• Burn wound infections 

• Clostridioides

• Colitis

• Croup

• Enterobacter infections 

• Enterococcal infections 

• E-coli infections

Prognosis

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

• The severity of illness at the time of diagnosis (eg., shock, coma, respiratory failure, acute respiratory distress syndrome)
• Bacteremia
• The underlying co-morbidities[10]