Methicillin-resistant Staphylococcus aureus (MRSA)

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Methicillin-resistant Staphylococcus aureus (MRSA)

Dirk M. Elston

Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports

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Management strategy

Healthcare-type strains of methicillin-resistant Staphylococcus aureus (MRSA) are associated with sepsis and are common colonists of chronic wounds, where debridement is typically the best strategy. Community-type MRSA infections typically present as an abscess or furunculosis. The most important intervention for an abscess remains surgical drainage. Purulent material can reform rapidly, so a punch or cruciate incision is advised, as it tends to remain open longer to allow adequate drainage. A curette is used to probe the wound and ensure that all pockets of purulent material have been adequately drained. Irrigation can be helpful, but packing is discouraged as purulent material often reforms behind the packing material. Evidence suggests that antibiotics are often unnecessary if an abscess is adequately drained. There are obvious reasons to avoid antibiotics when they are not needed, including the risk of Stevens–Johnson syndrome, antibiotic associated diarrhea, and selection of resistant strains.

Patients with significant surrounding cellulitis, refractory infection or systemic manifestations may require antibiotic therapy. Most community-associated (CA)-MRSA strains are sensitive to trimethoprim–sulfamethoxazole. Most strains are also sensitive to doxycycline and minocycline, but doxycycline does not penetrate well into the nares. Clindamycin resistance is emerging in many communities. For serious infections, therapy should be guided by culture and sensitivity. Vancomycin, linezolid, dalbavancin, telavancin, and daptomycin are often effective. Rifampin improves intracellular killing of bacteria by vancomycin. Quinupristin–dalfopristin and tigecycline may also be effective, but quinupristin–dalfopristin, like daptomycin, may not penetrate reliably into pulmonary tissue and tigecycline has a significant incidence of nausea. Ceptobiprole and oritavancin appear promising.

Spread occurs through skin-to-skin contact and via fomites. Decolonization may be indicated for prevention of recurrence or prevention of serious invasive disease in close contacts. The most effective decolonization regimens address the nares, intertriginous and anogenital sites, as well as eczematous skin. In some patients, gut colonization may also be an issue.

Specific investigations

Cultures should be obtained from the contents of purulent infections and resistant infections. New molecular diagnostic tests are being developed to screen for MRSA and identify genes associated with resistance.

Clinical importance of purulence in methicillin-resistant Staphylococcus aureus skin and soft tissue infections.

Crawford SE, David MZ, Glikman D, King KJ, Boyle-Vavra S, Daum RS. J Am Board Fam Med 2009; 22: 647–54.

In a study of 262 patients with purulent skin and soft tissue infections performed at the University of Chicago Medical Center, 253 (97%) contained the staphylococcal chromosomal cassette mec (SCCmec) IV and 245 (94%) contained Panton-Valentine leukocidin (pvl) genes, both common characteristics of community-associated MRSA strains. 231 of the isolated strains (88%) were susceptible to clindamycin. In contrast, among the 87 isolates from non-purulent infections, only 44% were susceptible to clindamycin.

These data suggest that, at least in Chicago, purulent MRSA infections are more likely to be caused by clindamycin-susceptible isolates.

First-line therapy

Treatment of MRSA abscesses
image Surgical drainage alone B
image Surgical drainage plus  
 – trimethoprim–sulfamethoxazole B
 – minocycline B
 – doxycycline B
 – clindamycin B
Eradication of colonization: nares
image Mupirocin B
image Tea tree oil B
Eradication of colonization: skin
image Bleach baths D
image Chlorhexidine B
image Triclosan B
image Tea tree oil soap B
image Undecylenamidopropyltrimonium methosulphate/phenoxyethanol C
image Octenidine dihydrochloride C

image

Comparative effectiveness of antibiotic treatment strategies for pediatric skin and soft-tissue infections.

Williams DJ, Cooper WO, Kaltenbach LA, Dudley JA, Kirschke DL, Jones TF, et al. Pediatrics 2011; 128: e479–87.

In a study of 6407 children who underwent drainage for MRSA infections, there were 568 treatment failures (8.9%). The rate of recurrence was high (22.8%). The adjusted odds ratios for treatment failure were 1.92 (95% confidence interval [CI]: 1.49–2.47) for trimethoprim–sulfamethoxazole and 2.23 (95% CI: 1.71–2.90) for β-lactams. Among the 41 094 children without a drainage procedure, there were 2435 treatment failures (5.9%), but the rate of recurrence was similar to the rate in those who required drainage (18.2%). The adjusted odds ratios for treatment failure were 1.67 (95% CI: 1.44–1.95) for trimethoprim–sulfamethoxazole and 1.22 (95% CI: 1.06-–1.41) for β-lactams. The authors concluded that, compared with data for clindamycin, use of both trimethoprim–sulfamethoxazole or β-lactams was associated with an increased risk of treatment failure.

MRSA abscesses typically respond to drainage alone, and it is the adequacy of the drainage procedure rather than the choice of antibiotic that is the prime determinant of outcome. It would also be important to know the local prevalence of inducible clindamycin resistance prior to recommending clindamycin over TMP-SMZ when an antibiotic is needed.

Children with atopic dermatitis appear less likely to be infected with community acquired methicillin-resistant Staphylococcus aureus: the San Diego experience.

Matiz C, Tom WL, Eichenfield LF, Pong A, Friedlander SF. Pediatr Dermatol 2011; 28: 6–11.

This study compared the rates CA-MRSA and methicillin-susceptible. Staphylococcus aureus skin and soft tissue infections in children with atopic dermatitis compared to the general pediatric population. The children with atopic dermatitis had a much lower rate of CA-MRSA infection compared with the general pediatric population. Clindamycin-inducible resistance was very low in both groups.

Abscesses that respond primarily to drainage and other skin infections are still predominantly caused by methicillin-sensitive staphylococci and streptococci. Inexpensive β-lactam drugs remain an excellent empiric choice for most skin infections, including those in atopic patients. Clindamycin remains a good alternative that covers both staphylococci and streptococci.

Trimethoprim–sulfamethoxazole or clindamycin for community-associated MRSA (CA-MRSA) skin infections.

Frei CR, Miller ML, Lewis JS 2nd, Lawson KA, Hunter JM, Oramasionwu CU, et al. J Am Board Fam Med 2010; 23: 714–19.

A retrospective cohort study of outpatients with skin and soft tissue infections showed that patients who did not receive incision and drainage were twice as likely to experience failure (57% vs 29%; p < 0.001). In this study, failure rates were lowest for incision and drainage plus an antibiotic. Among those who received incision and drainage, there were no significant differences between the TMP-SMX and clindamycin groups.

One would expect the choice of antibiotic to make the most difference for infections other than abscess. In scenarios such as cellulitis, where streptococci are common pathogens, clindamycin or a β-lactam may be a better initial choice than sulfa.

Targeted intranasal mupirocin to prevent colonization and infection by community-associated methicillin-resistant Staphylococcus aureus strains in soldiers: a cluster randomized controlled trial.

Ellis MW, Griffith ME, Dooley DP, McLean JC, Jorgensen JH, Patterson JE, et al. Antimicrob Agents Chemother 2007; 51: 3591–8.

A randomized, double-blind, placebo-controlled trial of intranasal mupirocin therapy in CA-MRSA-colonized soldiers found that 134 (3.9%) of the 3447 participants screened were colonized. Seven of 66 mupirocin-treated participants developed infections, compared with five of 65 placebo-treated participants. Despite eradication of nasal colonization, there was no decrease in infections and nasal eradication was ineffective in preventing new MRSA colonization in the study group.

Targeting the nares alone appears to be of little value. The skin and possibly the gastrointestinal tract are important reservoirs of MRSA.

Second-line therapy

image Vancomycin ± rifampin B
image Linezolid A
image Dalbavancin B
image Telavancin B
image Daptomycin B
Eradication of colonization: nares
image Retapamulin D
image Triple antibiotic ointment D
image Silver sulfadiazine cream D
Eradication of colonization: skin
image Benzoyl peroxide soap E
image Zinc pyrithione soap E

image

Linezolid and vancomycin in treatment of lower-extremity complicated skin and skin structure infections caused by methicillin-resistant Staphylococcus aureus in patients with and without vascular disease.

Duane TM, Weigelt JA, Puzniak LA, Huang DB. Surg Infect (Larchmt) 2012; 13: 147–53.

This study of patients with and without vascular disease treated with linezolid or vancomycin for a lower-extremity complicated MRSA skin and skin structure infection compared linezolid 600 mg intravenously (IV) or orally every 12 hours and vancomycin 15 mg/kg or 1 g IV every 12 hours. Among those with vascular disease (linezolid n = 139, vancomycin n = 135), the clinical success rate was 80.4% and 66.7% (p = 0.02) for linezolid and vancomycin, respectively. Among those without vascular disease (linezolid n = 91, vancomycin n = 112), the success rate was 94.5% and 89.4%, respectively (p = 0.24).

This study presents additional data suggesting outcomes with linezolid are better than those with vancomycin in serious MRSA infections. In this study, the linezolid-treated patients had fewer IV catheter-site complications and less renal impairment but more frequent thrombocytopenia than those who received vancomycin.

Antimicrobial susceptibility and molecular characteristics of 857 methicillin-resistant Staphylococcus aureus isolates from 16 medical centers in Japan (2008–2009): nationwide survey of community-acquired and nosocomial MRSA.

Yanagihara K, Araki N, Watanabe S, Kinebuchi T, Kaku M, Maesaki, et al. Diagn Microbiol Infect Dis 2012; 72: 253–7.

A recent Japanese survey of MRSA isolates, demonstrated a predominance of SCCmec type II (hospital type) strains. Community type IV stains accounted for 20%. The percentage of type IV isolates was significantly higher among outpatients. Most of the strains were sensitive to vancomycin (VCM, MIC ≤2 µg/mL), linezolid (MIC ≤4 µg/mL), and teicoplanin (MIC ≤8 µg/mL).

Community type stains have moved into hospitals, and vice-versa. Ambulatory patients are still more likely to have community strains. The majority of the isolates were sensitive to both vancomycin and linezolid.

In vitro pharmacokinetic/pharmacodynamic activity of NXL103 versus clindamycin and linezolid against clinical Staphylococcus aureus and Streptococcus pyogenes isolates.

Vidaillac C, Parra-Ruiz J, Winterfield P, Rybak MJ. Int J Antimicrob Agents 2011; 38: 301–6.

NXL103 (linopristin/flopristin, 30/70) is a novel oral streptogramin combination with activity against a large variety of multidrug-resistant Gram-positive pathogens. This study compared the in vitro activity of NXL103 with clindamycin and linezolid against four MRSA and two Streptococcus pyogenes isolates. NXL103 demonstrated significantly better activity than linezolid or clindamycin and was bactericidal.

This promising combination shows activity against both MRSA and Streptococcus pyogenes strains, including those resistant to clindamycin.

Third-line therapies

image Tigecycline B
image Ceptobiprole, ceftaroline C
image Oritavancin C
image Honey D
image Confectioner’s sugar E
image Sugar and povidone iodine E
image Botanical extracts D

Activity of oritavancin and comparators in vitro against standard and high inocula of Staphylococcus aureus.

Arhin FF, Sarmiento I, Parr TR Jr, Moeck G. Int J Antimicrob Agents 2012; 39: 159–62.

In a study of the impact of inoculum density on the growth inhibitory and killing activities of oritavancin, vancomycin, daptomycin and linezolid against four Staphylococcus aureus strains, minimal inhibitory concentrations (MICs) of the comparators were two- to eightfold higher when tested against a high inoculum. Oritavancin MICs were 16-fold higher for all strains at the high inoculum relative to the standard inoculum. However, in time-kill assays, oritavancin retained its bactericidal activity at both standard and high inocula.

In infections with a high concentration of organisms, different dosing and combinations of agents may be needed.

Results of a double-blind, randomized trial of ceftobiprole treatment of complicated skin and skin structure infections caused by Gram-positive bacteria.

Noel GJ, Strauss RS, Amsler K, Heep M, Pypstra R, Solomkin JS. Antimicrob Agents Chemother 2008; 52: 37–44.

In a randomized, double-blind trial of ceftobiprole 500 mg every 12 hours versus vancomycin 1 g every 12 hours (282 receiving ceftobiprole and 277 receiving vancomycin), 91.8% of the MRSA patients treated with ceftobiprole and 90.0% of those treated with vancomycin were cured (95% CI of difference, −8.4%, 12.1%). Adverse events were common and included nausea (14%) and taste disturbance (8%).

Ceftobiprole is a broad-spectrum cephalosporin active against MRSA. Although adverse effects were common, the rate was similar to that with vancomycin, and the drug had to be discontinued because of side effects in only 4% of patients.

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