The Role of β-Hemolytic Streptococci in Causing Diffuse, Nonculturable Cellulitis

Abstract

Staphylococcus aureus and beta-hemolytic streptococci (BHS) are the 2 main types of bacteria causing soft-tissue infections. Historically, BHS were believed to be the primary cause of diffuse, nonculturable cellulitis. However, with the recent epidemic of community-associated methicillin-resistant S aureus (MRSA) causing culturable soft-tissue infections, it is currently unclear what role either of these bacteria has in cases where the cellulitis is diffuse and nonculturable. This uncertainty has led to broad-spectrum and haphazard use of antibiotics for this infection type, which has led to increased risk of adverse drug reactions, health care costs, and emergence of resistance in bacteria. To investigate this issue, we conducted a prospective investigation between December 2004 and June 2007, enrolling all adult patients admitted to the inpatient service at the Olive View-UCLA Medical Center, a county hospital of Los Angeles, with diffuse, nonculturable cellulitis. Acute and convalescent serologies for anti-streptolysin-O and anti-DNase-B antibodies were obtained. Patient data were analyzed for response to beta-lactam antibiotics. The primary outcome was the proportion of these cases caused by BHS, as diagnosed by serologies and/or blood cultures, and the secondary outcome was the response rate of patients to beta-lactam antibiotics. Of 248 patients enrolled, 69 were dropped from analysis because of loss to follow-up or exclusion criteria. Of the 179 remaining patients, 73% of nonculturable cellulitis cases were caused by BHS. Analysis of outcomes to beta-lactam antibiotic treatment revealed that patients diagnosed with BHS had a 97% (71/73) response, while those who did not have BHS had a 91% (21/23) response, with an overall response rate of 95.8% (116/121). Results of this large, prospective study show that diffuse, nonculturable cellulitis is still mainly caused by BHS, despite the MRSA epidemic, and that for this infection type, treatment with beta-lactam antibiotics is still effective. A cost-effective, evidence-based algorithm can be useful for the empiric management of uncomplicated soft-tissue infections based on the presence or absence of a culturable source.

Hospitalist Perspective on the Treatment of Skin and Soft Tissue Infections

“…5 S aureus is one of the most predominant organisms, causing 44.6% to 46.9% of SSTIs, 6,28 particularly cellulitis that is purulent and associated with abscesses. 9,14 Among S aureus isolated from SSTIs, MRSA prevalence is high (35.9%-56.8%).…”

“…4 The most common organisms that cause SSTIs are Staphylococcus aureus and Streptococcus species. 5,6 Methicillin-resistant S aureus (MRSA) is a predominant pathogen that causes SSTIs, is associated with increased length of hospitalization, and is an independent risk factor for increased mortality and hospital charges compared with methicillin-susceptible S aureus (MSSA). 7,8 The increasing incidence of SSTIs in both ambulatory and hospital settings, coupled with the increase of MRSA as a causative pathogen, demands optimal management of these infections to improve outcomes.…”

Specific PCR, bacterial culture, serology and pharyngeal sampling to enhance the aetiological diagnosis of cellulitis

“…This study used a combination of PCR from skin swabs, skin swab culture, throat swab culture and serology to detect evidence of GAS or S. aureus in clinical cases of cellulitis; other studies have used immunofluorescence of skin biopsies (Bernard et al, 1989), PCR of tissue aspirates (Johnson et al, 2012) and serology (Jeng et al, 2010;Karppelin et al, 2014;Leppard et al, 1985). Despite this wide repertoire of testing, we were unable to achieve a confirmed bacteriological diagnosis in as many patients as those using serology alone.…”

“…The most likely reason for our poorer diagnostic yield from serology is the short period between the acute and convalescent samples. The two most recent previous studies had a period of 4 weeks (Karppelin et al, 2014) and 2-12 weeks (Jeng et al, 2010) between sampling. Our trial follow-up was limited to 10 days, and this may be insufficient time to generate a detectable difference between samples, especially as we were unable to determine absolute antibody values.…”

“…The bacterial aetiology of limb cellulitis is largely attributed to group A Streptococcus (GAS) and Staphylococcus aureus, but it is often difficult to get bacteriological confirmation (Jeng et al, 2010). As part of a National Institute for Health Research-funded clinical trial; Adjunctive Clindamycin for Cellulitis (C4C) trial (EudraCT Number: 2013-001218-14, ISRCTN: 86329346), which aims to evaluate the role of clindamycin in addition to flucloxacillin for the treatment of cellulitis, we wanted to secure a bacteriological aetiology in order to be able to increase our ability to generalize the findings to other GAS infections.…”