Pneumonia Caused by Methicillin-Resistant Staphylococcus aureus
Ethan Rubinstein Marin H. Kollef Dilip Nathwani
Clinical Infectious Diseases, Volume 46, Issue Supplement_5, 1 June 2008, Pages S378–S385, https://doi.org/10.1086/533594
Published: 01 June 2008
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Abstract
A recent increase in staphylococcal infections caused by methicillin-resistant Staphylococcus aureus (MRSA), combined with frequent, prolonged ventilatory support of an aging, often chronically ill population, has resulted in a large increase in cases of
MRSA pneumonia in the health care setting. In addition, community-acquired MRSA pneumonia has become more prevalent. This type of pneumonia historically affects younger patients, follows infection with influenza virus, and is often severe, requiring
hospitalization and causing the death of a significant proportion of those affected. Ultimately, hospital-acquired MRSA and community-acquired MRSA are important causes of pneumonia and present diagnostic and therapeutic challenges. Rapid institution of
appropriate antibiotic therapy, including linezolid as an alternative to vancomycin, is crucial. Respiratory infection–control measures and de-escalation of initial broad-spectrum antibiotic regimens to avoid emergence of resistant organisms are also
important. This article reviews the clinical features of, diagnosis of, and therapies for MRSA pneumonia.

Topic: vancomycin pneumonia diagnosis linezolid methicillin-resistant staphylococcus aureus methicillin-resistant staphylococcal aureus pneumonia
Issue Section: supplement articles
Until recently, staphylococcal pneumonia was considered an uncommon community-acquired pneumonia (CAP), accounting for 1%–5% of all CAP cases and occurring primarily in patients with influenza [1]. In addition, Staphylococcus aureus was recognized as
an important but infrequent cause of nosocomial pneumonia, occurring especially in elderly persons [2, 3]. However, in the past 2 decades, there have been important changes in S. aureus pulmonary infection. First, most large medical centers in the United
States have seen a dramatic increase in the percentage of staphylococcal infections caused by methicillin-resistant S. aureus (MRSA). At the same time, frequent and prolonged ventilatory support of an aging, often chronically ill population has become
commonplace. The intersection of these developments has fueled a dramatic increase in cases of MRSA pneumonia. Indeed, MRSA now accounts for 20%–40% of all hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). Until recently,
most of the MRSA strains causing health care–associated pneumonia (HCAP), HAP, and VAP were labeled hospital-acquired MRSA (HA-MRSA) and contained the staphylococcal cassette chromosome (SCC) mec types I–III [4, 5]. Recently, however, a new variant
of MRSA has emerged as a pulmonary pathogen. This new variant of S. aureus that causes pneumonia is community-acquired MRSA (CA-MRSA), containing SCCmec type IV.

CA-MRSA, although primarily a cause of skin and soft-tissue infection, has proved to be a formidable cause of pneumonia. In France in 2002, Gillet et al. [6] described 16 cases of CAP caused by CA-MRSA containing SCCmec type IV, as well as the gene
encoding Panton-Valentine leukocidin (PVL), a toxin that destroys polymorphonuclear leukocytes. The patients were young (median age, 14.8 years), the pneumonia was frequently preceded by an influenza-like illness, the disease course was stormy, and the
48-h survival rate was 63% (figure 1). The lethal potential of this postinfluenza pneumonia was confirmed in the United States [7].

Figure 1
Probability of survival of patients with staphylococcal pneumonia, according to whether the pathogenic strain was positive or negative for the Panton-Valentine leukocidin (PVL) gene. Reprinted from [6], with permission from Elsevier.
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Probability of survival of patients with staphylococcal pneumonia, according to whether the pathogenic strain was positive or negative for the Panton-Valentine leukocidin (PVL) gene. Reprinted from [6], with permission from Elsevier.

Recently, CA-MRSA has moved into the health care setting. This migration has been quite variable among hospitals, regions, and countries and has made the epidemiologic differentiation of CA-MRSA and HA-MRSA genotypes particularly difficult. The
significance of this epidemiologic shift remains unknown. Although the point has been debated, PVL, commonly associated with CA-MRSA, has been considered a virulence factor associated with severe pneumonia. There may be other factors that increase the
virulence of CA-MRSA and HA-MRSA strains, causing the morbidity and mortality of staphylococcal pneumonia to increase dramatically.

Overall, MRSA is an important cause of pneumonia. A survey of 59 US hospitals, involving 4543 patients with culture-positive pneumonia, between January 2002 and January 2004 [5] identified MRSA as a potential pathogen in 8.9% of CAP cases, 26.5% of HCAP
cases, 22.9% of HAP cases, and 14.6% of VAP cases. Indeed, in this study, S. aureus was identified by logistic regression analysis as the only pathogen independently associated with mortality.

Clinical Features
HCAP, HAP, and VAP. Patients who develop staphylococcal pneumonia while in nursing homes or extended-care facilities (i.e., HCAP) or in hospitals (i.e., HAP and VAP) are often infected with HA-MRSA. These patients are frequently elderly and have
significant underlying diseases. Staphylococcal pneumonia in these patients is clinically similar to HCAP, HAP, and VAP secondary to gram-negative organisms. Bacteremia in patients with staphylococcal pneumonia occurs late (mean onset, 9 days after the
onset of pneumonia symptoms) during the course of HAP or VAP [8]. These pneumonia cases are associated with an all-cause mortality of 55.5%, despite early and appropriate therapy.

CAP. Pneumonia in young, previously healthy adults with a preceding influenza-like illness characterized by severe respiratory symptoms, hemoptysis, high fever, leukopenia, very high C-reactive protein level (>400 g/L), hypotension, and a chest x-ray
showing multilobular cavitating alveolar infiltrates should lead one to suspect CA-MRSA infection [6, 7, 9–13] (figure 2). Young age has been a remarkable feature of CA-MRSA pneumonia in both European and US series [6, 7, 14]. Importantly, preceding
influenza or influenza-like illness has been described in 75% of cases [6, 7]. The severity of these pneumonia cases is demonstrated by the fact that, in one series, 81% of hospitalized patients needed to be admitted to the intensive care unit, 62%
required intubation, 46% had chest tube placement, and 29% died [7].

Figure 2
Chest x-ray and CT scan of the chest of a young patient with community-associated methicillin-resistant Staphylococcus aureus pneumonia. Reprinted from [13], with permission from the American College of Chest Physicians.
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Chest x-ray and CT scan of the chest of a young patient with community-associated methicillin-resistant Staphylococcus aureus pneumonia. Reprinted from [13], with permission from the American College of Chest Physicians.

From December 2006 through January 2007, 10 additional cases of MRSA CAP were reported from the southern United States in young, healthy, patients with preceding influenza or influenza-like illness (table 1) [15]. Six of the 10 patients died a mean of 3.
5 days after the onset of symptoms. All tested isolates (isolates from 5 of the 10 patients) were positive for PVL and carried SCCmec type IVa. All isolates had an indistinguishable PFGE pattern, and all belonged to the USA300-0114 clone group. All
isolates were resistant to β-lactams and erythromycin, 2 strains had inducible resistance to clindamycin, and 2 strains were not susceptible to levofloxacin [15].

Table 1
Factors associated with 10 cases of community-acquired pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) reported to the Centers for Disease Control and Prevention (CDC), 2006–2007.
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Factors associated with 10 cases of community-acquired pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) reported to the Centers for Disease Control and Prevention (CDC), 2006–2007.

Diagnosis

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https://academic.oup.com/cid/article/46/Supplement_5/S378/474128

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