US Pharm. 2010;35(7):HS-2-HS-4.
Nosocomial pneumonia, the second leading cause of hospital-acquired infections in the United States, has the highest morbidity and mortality rates of all hospital-acquired infections. All-cause mortality rates are as high as 70% among patients receiving mechanical ventilation. Nosocomial pneumonia is categorized into hospital-acquired pneumonia (HAP), health care (HC)-associated pneumonia (HCAP), and ventilator-associated pneumonia (VAP).1 This article reviews the epidemiology, clinical characteristics, diagnosis, risk factors, prevention, and treatment of nosocomial pneumonia. Finally, the pharmacist's role in managing this disease is discussed.
Nosocomial pneumonia, whether HAP, HCAP, or VAP, has a profound impact on the HC system and is an important cause of morbidity and mortality despite preventive measures and improvements in technology and antimicrobial therapy.2 HAP is defined as pneumonia occurring 48 or more hours after admission that was not incubating at the time of admission. HCAP includes any patient who was hospitalized in an acute-care hospital for more than 2 days or in a long-term care facility (LTCF); received recent IV antibiotic therapy, chemotherapy, or wound care within the past 30 days of infection; or attended a hospital or hemodialysis clinic. VAP is pneumonia that occurs 48 to 72 hours after endotracheal intubation.1-4 The goal of therapy is to initiate appropriate antibiotics at the appropriate doses and duration based on microbiologic cultures, if available. Clinicians should recognize interinstitution variability and consider local microbiologic data when recommending specific antimicrobials for patients with pneumonia.
Current estimates indicate that HAP occurs at a rate of 5 to 10 cases per 1,000 hospitalizations.1 Hospital length of stay increases in HAP patients by an average of 7 to 9 days per patient, and the estimated cost exceeds $40,000 per patient.1 HAP is responsible for approximately 25% of all ICU infections and for more than 50% of antibiotics prescribed. Time of onset can be a predictor of outcome, as early-onset HAP is associated with a better prognosis, largely owing to bacteria that are more susceptible to antibacterial agents. Late-onset HAP (
>5 days) is more frequently caused by multidrug-resistant (MDR) organisms. Although the mortality rate associated with HAP may be as high as 30% to 70%, many critically ill patients with HAP die as a result of the underlying disease, not the pneumonia.2
Numerical estimates for HCAP are difficult to determine since HCAP encompasses nursing home residents, dialysis patients, patients receiving home infusion therapy or wound care, patients undergoing chemotherapy, patients hospitalized in the last 90 days, and patients with a relative who is harboring an MDR infection.3 However, current estimates indicate that the annual incidence of pneumonia among long-term care facility (LTCF) residents is 99 to 912 per 1,000 persons (median 365/1,000), with a hospitalization rate 30 times higher than the general population.3 Although a specific estimate of the incidence of dialysis-associated pneumonia was not located, pneumonia is common in hemodialysis patients and is associated with a high mortality rate. Approximately 15% to 25% of patients with profound neutropenia after intensive chemotherapy experience pulmonary infiltrates, and these patients have a high rate of mortality. No epidemiologic data were located for patients receiving home infusion therapy or wound care, patients with a prior hospitalization in the last 90 days, or patients with a relative harboring an MDR infection. Although HCAP patients are relatively similar to HAP patients with respect to age, functional status, and number and severity of comorbidities, slight differences exist in the populations of patients affected with HCAP. LTCF patients who have experienced large-volume aspirations and sedative medications have an increased risk of HCAP. Mortality rates for HCAP range from 10% to 20%.3
Current estimates indicate that VAP occurs in 9% to 27% of all intubated patients, and in ICU patients nearly all cases (90%) occur when patients are mechanically ventilated. The highest risk of VAP occurs within the first 5 days of ventilation, and approximately 50% of all episodes occur within the first 4 days of mechanical ventilation. Early-onset VAP is typically associated with a better prognosis, as these infections are less likely to be caused by antibiotic-resistant organisms. Late-onset (³5 days) infections are more likely caused by MDR pathogens.2
Common pathogens for HAP include aerobic gram-negative bacilli (e.g., Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Acinetobacter species (spp). Although infections with gram-positive organisms such as Staphylococcus aureus have been developing, pneumonia due to S aureus is more common in patients with diabetes mellitus, those with head trauma, and those hospitalized in the ICU.2 The most common microorganisms yielded in HCAP infections are S aureus, methicillin-resistant S aureus (MRSA), and P aeruginosa. Early VAP is associated with microorganisms currently encountered in community-acquired pneumonia (CAP) (e.g., Haemophilus influenzae, Streptococcus pneumoniae, S aureus). Late VAP is associated with Pseudomonas spp, Acinetobacter spp, and MRSA.5
Risk Factors and Prevention
Risk factors for HAP are categorized as modifiable or nonmodifiable. Some risk factors are patient-related (e.g., male sex, pre-existing pulmonary disease, multiple organ system failure) or treatment-related (intubation, enteral feeding). Modifiable risk factors are suitable for prevention and involve infection control; alcohol-based disinfection; use of microbiologic surveillance for local MDR pathogens; monitoring and removal of IV devices; and initiation of programs to reduce or alter antibiotic prescribing practices.2 Enteral nutrition is a risk factor for the development of HAP owing to the increased risk of aspiration of gastric contents. A meta-analysis indicated that postpyloric feeding was associated with a significant reduction in HAP acquired in the ICU setting (RR 0.76; 95% CI 0.59-0.99).6 Although selective decontamination of the digestive tract has been considered as a preventive measure for the development of HAP, this procedure may increase the number of antibiotic-resistant microorganisms.2
Several medications known to increase the pH of the stomach contents have been reported to be independent risk factors for HAP, including H2 antagonists, antacids, and proton pump inhibitors (PPIs).2,7,8 Several studies assessing the increased risk of nosocomial pneumonia due to PPIs in critically ill patients have had conflicting results.7,8 Beaulieu et al evaluated whether the use of gastric acid-suppressive agents increased the risk of nosocomial pneumonia in a medical ICU in a retrospective cohort study of 787 patients.7 It was concluded that prior use of a PPI was not associated with a significant increase in the risk of developing nosocomial pneumonia.7 Miano et al evaluated the risk of nosocomial pneumonia with pantoprazole or ranitidine in a retrospective review of cardiothoracic surgery patients.8 Patients receiving pantoprazole (n = 377) had a higher risk of nosocomial pneumonia than patients receiving ranitidine (n = 457; OR 2.7%; 95% CI 1.1-6.7; P = .034).8
Some patients may be at increased risk for MDR pathogens. Risk factors include antimicrobial therapy in the preceding 90 days, current hospitalization for at least 5 days, and high frequency of antibiotic resistance in the community or hospital unit.4
Risk factors for MDR infection in HCAP patients include presence of a chronic indwelling device; prior antibiotic use in the last 3 months; chronic and advanced pulmonary diseases; and history of alcoholism and immunosuppression.3 Patients with HCAP also have several risk factors for MDR pathogens, including hospitalization for 2 or more days in the preceding 90 days; residence in a nursing home or extended-care facility; home infusion therapy (including antibiotics); chronic dialysis within 30 days; home wound care; a family member with infection involving an MDR pathogen; and immunosuppressive disease and/or therapy.4
Risk factors for VAP are the same as for other types of pneumonia. However, intubation and mechanical ventilation increase the risk of pneumonia six- to 21-fold and should be avoided whenever possible.2 Procedures to hasten weaning and improved methods of sedation reduce the risk of VAP.2 Specific types of endotracheal tubes have been associated with a reduction in the rate of VAP.2 Subglottic secretions should be aspirated continuously, and contaminated condensate should be emptied from ventilator circuits to prevent colonization of the tubing.2
Clinical Characteristics and Diagnosis
Clinical characteristics of pneumonia vary between the classifications and the patient populations affected. HAP is characterized by a radiographic infiltrate that is new or progressive plus clinical signs of infection (e.g., new-onset fever, leukocytosis, purulent sputum, decline in oxygen). Definitive diagnosis is complex owing to the difficulty in obtaining samples of lower respiratory tract secretions.2
The clinical presentation of HCAP may be different from what is typically observed in other pneumonia classifications owing to a variety of factors, including advanced age, presence of multiple chronic disease states, and differences in neurologic disorders.9 Typical symptoms in elderly patients (e.g., cough, expectorations, dyspnea, pleuritic chest pain) are mild and less frequent in younger patients. In addition, symptoms in older patients may be present for a longer duration compared with younger patients. Other symptoms in elderly patients may include mental confusion and gastrointestinal disorders (e.g., anorexia, nausea, vomiting, abdominal pain). Owing to the reduced ability of elderly patients to mount an immune response, fever is less commonly present in older patients. HCAP patients typically have a worse clinical presentation than CAP patients.8
In addition to the above diagnostic criteria, patients with suspected VAP should have blood cultures collected to evaluate potential microorganisms.2 A meta-analysis was conducted to evaluate different methods of VAP prevention.10 The use of oral decontamination (e.g., chlorhexidine solution in various concentrations, oral care with chlorhexidine) was assessed, and conflicting results were revealed. One analysis indicated that no significant reduction in VAP was observed; however, other studies indicated beneficial effects of chlorhexidine. Nasopharynx and oropharynx rinsing of 20 mL of povidone-iodine solution 10% was associated with beneficial effects.11 In the meta-analysis, no evidence was available to support closed or open systems to avoid VAP.10 Various infection-control methods revealed a range of improvement in VAP rates from 31% to 57%.10
Although community-acquired MRSA infections appear to be more virulent than HC-associated infections, early diagnosis is important in guiding empirical therapy.12 MRSA strains are responsible for up to 20% to 55% of cases of HAP and VAP.13 However, distinguishing HC-associated MRSA infections from methicillin-sensitive injections or other pathogens may be difficult. Evidence is conflicting regarding whether mortality rates for MRSA pneumonia are higher than those for methicillin-susceptible S aureus infections.12
Selection of the appropriate therapy is of paramount importance to the prognosis, as a delay in the initiation of appropriate antibiotic therapy in HAP patients is associated with increased mortality. Antibiotic therapy should be selected based on risk factors for specific organisms, knowledge of local patterns of antibiotic resistance, and the prevalence of offending organisms. Therapy should be modified based on clinical response on days 2 and 3 and appropriate cultures of lower respiratory tract secretions. TABLES 1 and 2 outline empiric antibiotic therapy in patients with and without known risk factors for MDR pathogens.2,14,15
Role of the Pharmacist
Pharmacists can be instrumental in helping determine the appropriate antibiotic therapy for patients with nosocomial pneumonia. Practice guidelines aid with empiric therapy for HCAP, and new guidelines will be available from the Infectious Diseases Society of America in autumn 2010.16 Recognition of patients with increased risk factors for HCAP may lead to improved outcomes through selection of the most appropriate agents.
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3. Polverino E, Torres A. Current perspective of the HCAP problem: is it CAP or is it HAP? Semin Respir Crit Care Med. 2009;30:239-248.
4. Anand N, Kollef MH. The alphabet soup of pneumonia: CAP, HAP, HCAP, NHAP, and VAP. Semin Resp Crit Care Med. 2009;30:3-9.
5. Aarts MA, Hancock JN, Heyland D, et al. Empiric antibiotic therapy for suspected ventilator-associated pneumonia: a systematic review and meta-analysis of randomized trials. Crit Care Med. 2008;36:108-117.
6. Heyland DK, Drover JW, MacDonald S, et al. Effect of postpyloric feeding on gastroesophageal regurgitation and pulmonary microaspiration: results of a randomized controlled trial. Crit Care Med. 2001;29:1495-1501.
7. Beaulieu M, Williamson D, Sirois C, Lachaine J. Do proton-pump inhibitors increase the risk for nosocomial pneumonia in a medical intensive care unit? J Crit Care. 2008;23:513-518.
8. Miano TA, Reichert MG, Houle TT, et al. Nosocomial pneumonia risk and stress ulcer prophylaxis: a comparison of pantoprazole vs ranitidine in cardiothoracic surgery patients. Chest. 2009;136:440-447.
9. Polverino E, Torres A. Diagnostic strategies for health-care associated pneumonia. Semin Respir Crit Care Med. 2009;30:36-45.
10. Gastmeier P, Geffers C. Prevention of ventilator-associated pneumonia: analysis of studies published since 2004. J Hosp Infect. 2007;67:1-8.
11. Seguin P, Tanguy M, Laviolle B, et al. Effect of oropharyngeal decontamination by povidone-iodine on ventilator-associated pneumonia in patients with head trauma. Crit Care Med. 2006;34:1514-1519.
12. Tacconelli E, De Angelis G. Pneumonia due to methicillin-resistant Staphylococcus aureus: clinical features, diagnosis and management. Curr Opin Pulm Med. 2009;15:218-222.
13. Luna CM, Boyeras Navarro ID. Management of methicillin-resistant Staphylococcus aureus pneumonia. Curr Opin Infect Dis. 2010;23:178-184.
14. Park DR. Antimicrobial treatment of ventilator-associated pneumonia. Resp Care. 2005;50:932-952.
15. Clinical Pharmacology online database [subscription required]. http://clinicalpharmacology- 2008;21:380-389.
aspx?cpnum=638&sec=monindi. Accessed June 1, 2010.
16. Infectious Diseases Society of America. Hospital-acquired pneumonia (HAP). www.idsociety.org/content.
aspx?id=4430#hap. Accessed March 15, 2010.
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