Review
Expert Review of Respiratory Medicine Downloaded from informahealthcare.com by University of Queensland on 10/15/14 For personal use only.
Methicillin-resistant Staphylococcus aureus pneumonia in adults Expert Rev. Respir. Med. 8(5), 641–651 (2014)
Christian Woods* and Gene Colice Medstar Washington Hospital Center, Room 2A-38A, 110 Irving St NW, Washington, DC 20010, USA *Author for correspondence: Tel.: +1 202 877 7856 Fax: +1 202 877 0341 [email protected]
Methicillin-resistant Staphylococcus aureus (MRSA) has become one of the leading etiologies of nosocomial pneumonia as a result of an increase in staphylococcal infections caused by methicillin-resistant strains paired with extended ventilatory support of critically, and often, chronically ill patients. The prevalence of community-acquired MRSA pneumonia, which historically affects younger patients and is often preceded by an influenza-like illness, is also increasing. A high index of suspicion and early initiation of appropriate antibiotics are key factors for the successful treatment of this disease. Even with early diagnosis and appropriate treatment, MRSA pneumonia still carries an unacceptably high mortality rate. This article will review historical differences between hospital-acquired and community-acquired MRSA pneumonia, as well as, clinical features of, diagnosis and treatment of MRSA pneumonia. KEYWORDS: community-acquired pneumonia • hospital-acquired pneumonia • linezolid • methicillin-resistant Staphylococcus aureus • Panton–Valentine leukocidin • vancomycin • ventilator-associated pneumonia
Historically, Staphylococcus aureus was a rare cause of community-acquired pneumonia (CAP) accounting for 70% of patient had no underlying comorbid diseases. The mortality rate was 29% and four out of the five deaths in this study occurred in patients with pneumonia caused by MRSA. MRSA remains an important cause of pneumonia in both the community and the healthcare setting. Kollef et al. conducted a survey of 59 hospitals in the USA between January
2014 Informa UK Ltd
ISSN 1747-6348
641
Review
Woods & Colice
Expert Review of Respiratory Medicine Downloaded from informahealthcare.com by University of Queensland on 10/15/14 For personal use only.
Table 1. Classical characteristics of community-acquired methicillin-resistant Staphylococcus aureus versus hospital-acquired methicillin-resistant Staphylococcus aureus. CA-MRSA
HA-MRSA
Usual SCCmec type (clone)
IV and V (USA-300)
I, II and III (USA-100, USA-200)
PVL toxin
Common
Rare
Population commonly affected
Younger healthier; post-influenza
Older; more comorbidities; exposure to long-term care facilities
Antimicrobial resistance
b-lactam alone common Most susceptible to clindamycin and TMP/SMX
Resistance to multiple drug classes common
CA-MRSA: Community-acquired MRSA; HA-MRSA: Hospital-acquired MRSA; SCCmec: Staphylococcal cassette chromosome mec; TMP/SMX: Trimethoprim/ sulfamethoxazole. Data taken from [10–12,34–38].
2002 and January 2004 involving 4543 patients with cultureproven pneumonia [8]. MRSA was identified as the causative agent of pneumonia in 8.9% of CAP cases, 22.9% of HAP cases, 26.5% of healthcare-associated pneumonia (HCAP) cases and 14.6% of VAP cases. A recent study described the epidemiology and outcome of MRSA pneumonia in 11 Canadian hospitals in 2011 [9]. One hundred and sixty-one patients with MRSA pneumonia were identified. Of these 161 patients, 45 (28%) had CAP, 90 (56%) had HAP, 26 (16%) had HCAP and 23 (14%) had VAP. The mean (± standard deviation [SD]) incidence of MRSA HAP was 0.32 (± 0.26) per 10,000 patient-days, and of MRSA VAP was 0.30 (± 0.5) per 1000 ventilator-days. Comparison of CA-MRSA & hospital-acquired MRSA
There are key differences between CA-MRSA and hospitalacquired MRSA (HA-MRSA) (TABLE 1). CA-MRSA is distinguished from HA-MRSA by molecular testing. On pulse field gel electrophoresis, a majority of the HA-MRSA isolates were traditionally of the USA-100 or USA-200 clonal group. Nearly all MRSA isolates carry the mecA gene, which is part of a SCCmec. However, HA-MRSA strains tend to carry a large SCCmec that belongs to type I, II or III. They are usually resistant to most strains of non-b-lactam antibiotics. These strains also rarely carry the gene for PVL. In contrast, a majority of the CA-MRSA strain are of the USA-300 clonal group on pulse field gel electrophoresis. They tend to carry a smaller SCCmec of the type IV or V. They are resistant to fewer nonb-lactam classes of antibiotics and tend to frequently carry the PVL genes [10]. A retrospective study by Huang et al. reviewed all cases of MRSA isolated at a single institution from December 2003 through May 2004. Of the 283 documented MRSA 642
infections, 127 met the criteria for CA-MRSA. The USA-300 genotype accounted for 87% of all CA-MRSA cases, while the USA-100 genotype made up the largest proportion of HA-MRSA, accounting for 47% of cases. The CA-MRSA isolates were more likely to be susceptible to clindamycin (96 vs 48%; p < 0.001) and ciprofloxacin (53 vs 14%; p < 0.001) than HA-MRSA strains. This study also helped show that the distinction between CA-MRSA and HA-MRSA was becoming more problematic. Thirty-three percent of HAMRSA isolates were of the USA-300 genotype, and a sizable percentage of these isolates were susceptible to non-b-lactam classes of antibiotics [11]. A study conducted at the University of Chicago Hospitals from July 2004 through June 2005 further explored the relationship between the molecular profiles of HA- and CA-MRSA. Six hundred and sixteen MRSA infections were diagnosed. Of these, 404 (65.6%) had risk factors that would fulfill criteria for HAMRSA infection. Among these 404 isolates, 190 (47%) carried the PVL genes and 166 (41.1%) were susceptible to clindamycin. The conclusion of this study was that association with the healthcare environment has little predictive value for the molecular profiles and resistance patterns of MRSA [12]. Numerous studies have reported a similar increase in the percentage of typical HA-MRSA disease caused by genotype USA-300 [13–16]. The incidence of USA-300 genotype causing nosocomial disease was between 20 and 64% in these studies. This further supports the view that using exposure to the healthcare system, as the sole determinant of which MRSA genotypes are expected, is no longer a reliable method for categorization. The original CDC case definition for a CA-MRSA infection defined it as any MRSA infection for an outpatient or infection within 48 h of hospitalization if the patient lacked certain healthcare-associated risk factors, including residence in long-term care facility of hospitalization within previous year, hemodialysis, presence of indwelling catheter or percutaneous device at the time of culture, surgery or previous isolation of MRSA from the patient [17,18]. As a result of the increased prevalence of the USA-300 strain in HA-MRSA infections and the presence of HA-MRSA strains occurring in the community, CDC investigators created a third category for MRSA infection in 2006. The healthcare-associated, community-onset MRSA infections were cases that would meet the definition of HAMRSA by exposure but had their onset in the community [19]. The limitation of this definition is that exposure to the healthcare setting does not preclude acquisition of MRSA infection in the community setting. PVL & CA-MRSA
Van de Velde first described PVL in 1894 [20]. In 1932, Panton was able to show an association between the PVL and skin and soft tissue infections (SSTIs) [21]. Before the emergence of CA-MRSA in the early 1990s, the genes encoding PVL were thought to be present in 25% of VAP cases and have a diagnostic accuracy of
Expert Review of Respiratory Medicine Downloaded from informahealthcare.com by University of Queensland on 10/15/14 For personal use only.
Methicillin-resistant Staphylococcus aureus pneumonia in adults Expert Rev. Respir. Med. 8(5), 641–651 (2014)
Christian Woods* and Gene Colice Medstar Washington Hospital Center, Room 2A-38A, 110 Irving St NW, Washington, DC 20010, USA *Author for correspondence: Tel.: +1 202 877 7856 Fax: +1 202 877 0341 [email protected]
Methicillin-resistant Staphylococcus aureus (MRSA) has become one of the leading etiologies of nosocomial pneumonia as a result of an increase in staphylococcal infections caused by methicillin-resistant strains paired with extended ventilatory support of critically, and often, chronically ill patients. The prevalence of community-acquired MRSA pneumonia, which historically affects younger patients and is often preceded by an influenza-like illness, is also increasing. A high index of suspicion and early initiation of appropriate antibiotics are key factors for the successful treatment of this disease. Even with early diagnosis and appropriate treatment, MRSA pneumonia still carries an unacceptably high mortality rate. This article will review historical differences between hospital-acquired and community-acquired MRSA pneumonia, as well as, clinical features of, diagnosis and treatment of MRSA pneumonia. KEYWORDS: community-acquired pneumonia • hospital-acquired pneumonia • linezolid • methicillin-resistant Staphylococcus aureus • Panton–Valentine leukocidin • vancomycin • ventilator-associated pneumonia
Historically, Staphylococcus aureus was a rare cause of community-acquired pneumonia (CAP) accounting for 70% of patient had no underlying comorbid diseases. The mortality rate was 29% and four out of the five deaths in this study occurred in patients with pneumonia caused by MRSA. MRSA remains an important cause of pneumonia in both the community and the healthcare setting. Kollef et al. conducted a survey of 59 hospitals in the USA between January
2014 Informa UK Ltd
ISSN 1747-6348
641
Review
Woods & Colice
Expert Review of Respiratory Medicine Downloaded from informahealthcare.com by University of Queensland on 10/15/14 For personal use only.
Table 1. Classical characteristics of community-acquired methicillin-resistant Staphylococcus aureus versus hospital-acquired methicillin-resistant Staphylococcus aureus. CA-MRSA
HA-MRSA
Usual SCCmec type (clone)
IV and V (USA-300)
I, II and III (USA-100, USA-200)
PVL toxin
Common
Rare
Population commonly affected
Younger healthier; post-influenza
Older; more comorbidities; exposure to long-term care facilities
Antimicrobial resistance
b-lactam alone common Most susceptible to clindamycin and TMP/SMX
Resistance to multiple drug classes common
CA-MRSA: Community-acquired MRSA; HA-MRSA: Hospital-acquired MRSA; SCCmec: Staphylococcal cassette chromosome mec; TMP/SMX: Trimethoprim/ sulfamethoxazole. Data taken from [10–12,34–38].
2002 and January 2004 involving 4543 patients with cultureproven pneumonia [8]. MRSA was identified as the causative agent of pneumonia in 8.9% of CAP cases, 22.9% of HAP cases, 26.5% of healthcare-associated pneumonia (HCAP) cases and 14.6% of VAP cases. A recent study described the epidemiology and outcome of MRSA pneumonia in 11 Canadian hospitals in 2011 [9]. One hundred and sixty-one patients with MRSA pneumonia were identified. Of these 161 patients, 45 (28%) had CAP, 90 (56%) had HAP, 26 (16%) had HCAP and 23 (14%) had VAP. The mean (± standard deviation [SD]) incidence of MRSA HAP was 0.32 (± 0.26) per 10,000 patient-days, and of MRSA VAP was 0.30 (± 0.5) per 1000 ventilator-days. Comparison of CA-MRSA & hospital-acquired MRSA
There are key differences between CA-MRSA and hospitalacquired MRSA (HA-MRSA) (TABLE 1). CA-MRSA is distinguished from HA-MRSA by molecular testing. On pulse field gel electrophoresis, a majority of the HA-MRSA isolates were traditionally of the USA-100 or USA-200 clonal group. Nearly all MRSA isolates carry the mecA gene, which is part of a SCCmec. However, HA-MRSA strains tend to carry a large SCCmec that belongs to type I, II or III. They are usually resistant to most strains of non-b-lactam antibiotics. These strains also rarely carry the gene for PVL. In contrast, a majority of the CA-MRSA strain are of the USA-300 clonal group on pulse field gel electrophoresis. They tend to carry a smaller SCCmec of the type IV or V. They are resistant to fewer nonb-lactam classes of antibiotics and tend to frequently carry the PVL genes [10]. A retrospective study by Huang et al. reviewed all cases of MRSA isolated at a single institution from December 2003 through May 2004. Of the 283 documented MRSA 642
infections, 127 met the criteria for CA-MRSA. The USA-300 genotype accounted for 87% of all CA-MRSA cases, while the USA-100 genotype made up the largest proportion of HA-MRSA, accounting for 47% of cases. The CA-MRSA isolates were more likely to be susceptible to clindamycin (96 vs 48%; p < 0.001) and ciprofloxacin (53 vs 14%; p < 0.001) than HA-MRSA strains. This study also helped show that the distinction between CA-MRSA and HA-MRSA was becoming more problematic. Thirty-three percent of HAMRSA isolates were of the USA-300 genotype, and a sizable percentage of these isolates were susceptible to non-b-lactam classes of antibiotics [11]. A study conducted at the University of Chicago Hospitals from July 2004 through June 2005 further explored the relationship between the molecular profiles of HA- and CA-MRSA. Six hundred and sixteen MRSA infections were diagnosed. Of these, 404 (65.6%) had risk factors that would fulfill criteria for HAMRSA infection. Among these 404 isolates, 190 (47%) carried the PVL genes and 166 (41.1%) were susceptible to clindamycin. The conclusion of this study was that association with the healthcare environment has little predictive value for the molecular profiles and resistance patterns of MRSA [12]. Numerous studies have reported a similar increase in the percentage of typical HA-MRSA disease caused by genotype USA-300 [13–16]. The incidence of USA-300 genotype causing nosocomial disease was between 20 and 64% in these studies. This further supports the view that using exposure to the healthcare system, as the sole determinant of which MRSA genotypes are expected, is no longer a reliable method for categorization. The original CDC case definition for a CA-MRSA infection defined it as any MRSA infection for an outpatient or infection within 48 h of hospitalization if the patient lacked certain healthcare-associated risk factors, including residence in long-term care facility of hospitalization within previous year, hemodialysis, presence of indwelling catheter or percutaneous device at the time of culture, surgery or previous isolation of MRSA from the patient [17,18]. As a result of the increased prevalence of the USA-300 strain in HA-MRSA infections and the presence of HA-MRSA strains occurring in the community, CDC investigators created a third category for MRSA infection in 2006. The healthcare-associated, community-onset MRSA infections were cases that would meet the definition of HAMRSA by exposure but had their onset in the community [19]. The limitation of this definition is that exposure to the healthcare setting does not preclude acquisition of MRSA infection in the community setting. PVL & CA-MRSA
Van de Velde first described PVL in 1894 [20]. In 1932, Panton was able to show an association between the PVL and skin and soft tissue infections (SSTIs) [21]. Before the emergence of CA-MRSA in the early 1990s, the genes encoding PVL were thought to be present in 25% of VAP cases and have a diagnostic accuracy of
