Staphylococcal and Streptococcal Pneumonias

Omar H. Mohamedaly and Laura E. Crotty Alexander

Staphylococcus and Streptococcus are Gram-positive cocci responsible for a broad spectrum of human disease and are common causes of pneumonia. Staphylococci typically grow in clusters, whereas streptococci occur in pairs and chains. Recovery of staphylococci from sputum culture is more reliable than for streptococci since antibiotics administered prior to obtaining culture specimens commonly inhibit streptococcal growth more than staphylococci.

Staphylococci secrete various catalases, which can be used to discriminate among species. S. aureus, a common pathogen in humans, is coagulase positive, which distinguishes it from the common contaminants S. epidermidis and S. saprophyticus, S. aureus is common in healthcare-associated pneumonia (HCAP). It is isolated in 15% to 23% of HCAP cases, compared to 3% to 9% of community-acquired pneumonia (CAP) cases. The incidence of S. aureus pneumonia continues to rise in both the HCAP and CAP settings. Risk factors for infection with S. aureus reflect impairment of host defenses, which include lung structure derangements (e.g., cystic fibrosis and bronchiectasis) as well as immunological defects (e.g., diabetes mellitus, alcoholism or postinfluenza).

S. aureus pneumonia commonly presents with fever, productive cough, and pleuritic chest pain. Radiographic patterns include extensive bilateral consolidation and cavitary lesions, especially early in the disease course. Pleural effusions are common. Empyema complicates about 20% of S. aureus pneumonias and the incidence appears to be rising; national registry data show a 3.3-fold increase in staphylococcal empyema between 1996 and 2008. Bacteremia may complicate as many as 60% of all S. aureus pneumonias.

Since it was first identified in 1961 on the basis of resistance to semisynthetic penicillins, methicillin-resistant S. aureus (MRSA) has come to represent a large proportion of staphylococcal diseases: over 60% of S. aureus isolates from US intensive care units are MRSA. Use of antibiotics, especially fluoroquinolones and cephalosporins, increases the risk of MRSA colonization and infection. Mortality is higher in invasive disease caused by MRSA as compared to methicillin-sensitive S. aureus (MSSA), with an odds ratio of 1.93.

MRSA more commonly causes HCAP than CAP (26.5% vs. 8.9% in one survey of 59 US hospitals covering 4,543 patients); however, the incidence is rising in the community setting. In particular, influenza patients who develop S. aureus super-infection most commonly have MRSA. The USA300 strain is a community-acquired MRSA that has rapidly spread across the world and is likely to continue increasing in prevalence and severity. It is characterized by the presence of the arginine catabolic mobile element (ACME) and production of Panton–Valentine leukocidin (PVL), a bicomponent pore-forming toxin responsible for neutrophil lysis, adhesion to mucous membranes, and an inflammatory response mediated by NF-κB. There are conflicting data on the morbidity and mortality attributable to PVL-positive strains. Another S. aureus virulence factor, α-hemolysin, might be more directly responsible for pneumonia-related mortality. Further investigation of other virulence factors implicates the superantigens responsible for staphylococcal toxic shock syndrome in the development of necrotizing pneumonias, for example, the small secreted protein SEIX, which is encoded by mobile genetic elements that are easily transmitted horizontally among strains.

The initial antimicrobial choice for S. aureus should be guided by local patterns of resistance and the degree of suspicion for MRSA. It can be tailored to culture and sensitivity results once they are available. Vancomycin remains the antimicrobial of choice for MRSA coverage. Though resistance is rare, minimum inhibitory concentration (MIC) creep is an increasing problem that has given rise to vancomycin-intermediate S. aureus (VISA), whichrequires higher doses to achieve sufficient MIC. High vancomycin doses, however, can be problematic in critically ill patients with renal failure. One emerging source of resistance is β-lactam-induced vancomycin resistance (BIVR), the clinical implications of which are not fully apparent at this point. Line-zolid resistance has also been identified, but with stricter control of linezolid prescription practices, it has been kept from spreading. It is noteworthy the concentration of vancomycin in the alveolar epithelium is only 12% of the vancomycin plasma concentration, which is far less than the 415% noted with linezolid. Linezolid has the additional advantage that its volume of distribution is not affected by critical illness and volume shifts. However, a major clinical trial comparing vancomycin to linezolid for MRSA pneumonia treatment (ZEPHYR) did not demonstrate superiority of linezolid and had significant methodological flaws limiting its generalizability. The fifth-generation cephalosporins, ceftaroline and ceftobiprole, have some potential for MRSA treatment. They have been shown to be noninferior to the older cephalosporins and to linezolid.

Promising efforts are underway to develop vaccines against S. aureus. Several targets are being investigated, including PVL (despite the lack of a direct link to morbidity and mortality), cell surface proteins, and peptidoglycan cell wall components. Blockade of ADAM10 receptor binding by α-hemolysin has shown efficacy in protecting against lethal pneumonia in animal models. Multi-antigenic approaches to vaccination against S. aureus are likely to be developed in the future.

Although there are more streptococcal species than staphylococcal, only three, S. pyogenes, S. agalactiae, and S. pneumoniae, play a major role in human lung infection. Streptococci are classified by the pattern of hemolysis on blood agar culture media: α-hemolysis refers to partial or green hemolysis related to oxidation of iron in hemoglobin within red blood cells, β refers to complete hemolysis causing RBC rupture, γ refers to lack of hemolysis. β-hemolytic streptococci are further classified by Lancefield group: 20 serotypes named A to V (sans I and J), referring to the carbohydrate antigenic composition of their cell walls.

Group A streptococcus, S. pyogenes, is the etiologic organism of some of the most publicized diseases in medicine: streptococcal pharyngitis, necrotizing fasciitis (for which it earned the label “flesh-eating bacteria”), and toxic shock syndrome. It is also responsible for some of the most severe cases of CAP, although it fortunately remains a rare cause of CAP, accounting only for less than 1% of cases. Group A streptococcus outbreaks have occurred in nursing homes, in military recruitment facilities, and in families. Presenting symptoms include cough, fever, sore throat, pleuritic chest pain, and dyspnea. Group A streptococcal pneumonia is typically multilobar (59%). Parapneumonic effusion are more common in group A streptococcal pneumonia (23%) than in pneumonia caused by S. pneumoniae

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