Antibiotic Choices for Treatment of MRSA

by Stephanie Chieng

Introduction
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Methicillin-resistant Staphylococcus aureus (MRSA). Is a bacterial infection that is highly resistant to some antibiotics especially beta-lactams (eg penicillins, cephalosporins, carbapenems) Staph infections, occur most frequently among persons/staff in hospitals and healthcare facilities who have weakened immune systems- HA-MRSA (hos acquired) MRSA infections that are acquired by persons who have not been recently (within the past year) hospitalized or had a medical procedure are known as CA-MRSA infections (community acquired). It can be transmitted via person to person contact or come in contact with any objects that have been touched by MRSA infected or carrier.

HA-MRSA vs CA-MRSA

“Community Associated Methicillin Resistant StaphyococcusAureus (CA MRSA) –Guidelines for Management and Control of Transmission”, PPH 42160, October 2005, Wisconsin DFHS

Infections
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Skin & soft tissue infections (SSTIs) are the most commonly seen in MRSA infection. Cellulitis [infection of the skin or the fat and tissues that lie immediately beneath the skin, usually starting as small red bumps on the skin] Boils [pus-filled infections of hair follicles] Abscesses [collections of pus under the skin] Carbuncles [infections larger than an abscess ] Generally starts as small red bumps that resemble pimples, boils or spider bitescan turn into deep, painful abscesses that require surgical draining.

Infections (cont’)
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Can also penetrate into the body, causing potentially life-threatening infections in bones, joints, surgical wounds, the bloodstream, heart valves and lungs. Some severe & invasive staph infections include: Endocarditis, necrotising fasciitis, osteomyelitis, sepsis etc

MRSA Skin Infection
MRSA skin lesions may begin as small papules and then develop into larger pustules or abscesses with areas of necrosis and surrounding erythema. Lesions are often confused with spider bites- CA MRSA.

A ruptured MRSA cyst.

Treatment
1)Glycopeptides (vancomycin, teicoplanin) -Bactericidal activity against aerobic & anaerobic gram+ve bac including MRSA. -Dose: IV 1g bd; 500mg q6h Paed: 10mg/kg q6h IV over 1hr -However, emergence of MRSA with reduced susceptibility to glycopeptides – VRS, VISA -TDM is important to monitor efficacy of treatment & toxicity. Higher trough level may be required in MRSA strains with higher MIC. -S/e: nephrotoxicity & ototoxicity

JAC recommend upper limit of pre-dose levels might best be set at 15-20mg/L. However, lack of evidence of improve outcome does not justify an increase in levels of dose, but absence of toxicity suggests this change in levels may be acceptable.

Treatment
2)Linezolid (oxazolidinones)
-FDA approved for Tx of complicated skin infections & HA pneumonia due to MRSA in adults. -Dose: 600mg q12hrs for 10-14d orally/IV Paed: 10mg/kg 8H-12H oral/IV -Associated with a risk of dose- and duration- dependent reversible In a 140-site international trials, patients with presumed MRSA infection myelosuppression, principally thrombocytopenia. Hence, the importance (2/3 culture confirm) receivecounts in pts receiving it for > 2 weeks. of monitoring complete blood either IV Vanco 1g BD or linezolid 600mg BD, concluded both have similar duration twds mild- mod MRSA infections. Linezolid's -Manufacturer recommend max efficacy of up to 28 days only. oral dosing option widespread resistance, should be reserves for patients. Both -To limit potential for may allow earlier discharge of hospitalizeduse in more severe well tolerated. treatments are infections. -As it is a reversible MAO I, avoid tyramine- rick food eg mature cheese, yeast extracts, alcohol, fermented soya bean products.

A systemic review & meta-analysis this year showed no differences between vanco & linezolid Tx in SSTIs. But a trends twds higher effectiveness of linezolid was observed.

Treatment(cont’)
3)Clindamycin -FDA approved for Tx of serious infections due to S.Aureus. However, there are reports of clindamycin being used successfully to Tx CAMRSA -A D-zone test should be performed to identify inducible clindamycin resistance in S.Aureus isolates Dose: 150-300mg q6hrs orally; up to 450mg q6hrs in severe infections. Involves placement of erythromycin and clindamycin disks4.8g daily IV 0.6-2.7g daily (in 2-4 divided doses) up to in close promimity on an agar plate inoculated with a standardized suspension Paed: different doses based on age group Flattening of the clindamycin s/e: ABx associated colitis zone of inhibition in the area between the two disks (resulting in a D-shaped zone of inhibition) indicates the presence of inducible clindamycin resistance (positive D-zone test).

Treatment (cont’)
4) Fusidic Acid -Indicated for infection caused by staph including MRSA by KKM -Evidence supporting its efficacy is limited and does not support the use of it as monotherapy. Limited studies done on use of topical fusidic acid on MRSA. -Emergence of resistance twds fusidicwith co-trimoxazole in eradication Has been use in combination acid is increasing as well. -Dose: 250-500mg BD oral Paed: 15-20mg/kg 8H oral of nasal carriage of MRSA. 5) Rifampicin (only combination use) -Should not be used alone in MRSA infection as S.aureus strains easily develop resistance twds it. -As rifampicin achieves high concentration in mucosal surfaces, theoretical benefit of including it is that it may promote eradication of MRSA carriage. -Dose: Rifampicin was shown to be effective as adjunct therapy to 450-600mg as single dose oral Paed: 10-15mg/kg OD

vancomycin non-responsive cases (with MIC <1mg/L) of MRSA caused septicaemia in burn patients.

Treatment (cont)
6)Mupirocin 2% cream & ointment -Topical Mupirocin has been used as eradication of nasal MRSA colonisation. -However, a Cochrane review concluded there was insufficient evidence to support the use of topical/ systemic antimicrobial therapy for eradicating nasal or extra- nasal MRSA. -JAC proposed that more studies are needed to confirm whether mupirocin remains useful in clearing carriage of MRSA especially when low- level of mupirocin resistance is present. 7)Trimethoprim- Sulphamethoxazole -Is not FDA approved for any Tx of staph infection. However, medical literature contains several cases of successful use. -It has been shown to be effective against MRSA both in vitro and in vivo in mice, as well as in clinical reports on meningitis, septicemia, and endocarditis.

2 european animal trials concluded high dose co-trimoxazole is as efficacious as vancomycin in pneumonia caused by MRSA.

Treatment (new drugs)
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Recently, few new drugs available for Tx of MRSA Ceftobiprole- is the 5th generation cephalosporin; a recent multinational, randomized, double-blind trial, comparing IV ceftobiprole with vancomycin + ceftazidime showed similar clinical cure rate in MRSA. Telavancin- synthetic derivative of vancomycin; FDA approved for Tx of adults with complicated SSTI caused by susceptible Gram-positive bacteria, including MRSA.

Management SSTIs
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Cutaneous abscesses with no systemic signs (otherwise healthy patients) Incision & drainage Recent randomised, placebo-controlled trial in adult patients with deep skin absesses & surrounding cellulitis (majority which were caused by MRSA), Tx success rates were over 90% for pts Tx with incision & drainage alone. For small furuncles not amenable to incision & drainage or collection of material for culture, moist heat may be satisfactory to promote drainage.

Prevention

Practice good hygiene especially in community:
Keep hands clean by washing thoroughly with soap and water or using an alcohol-based hand sanitizer. Keep cuts and scrapes clean and covered with a bandage until healed. Avoid contact with other people’s wounds or bandages. Avoid sharing personal items such as towels or razors. Finish whole course of ABx to prevent resistance In hospital: Wash hands frequently, make sure that IV tubes and catheters are inserted under sterile conditions, eg wearing gloves and mask.

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References:
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http://www.nlm.nih.gov/medlineplus/ency/article/007261.htm Centers for Disease Control and Prevention. Overview of community-associated MRSA. October 26, 2007. Community Associated Methicillin Resistant StaphyococcusAureus (CA MRSA) –Guidelines for Management and Control of Transmission”, PPH 42160, October 2005, Wisconsin DFHS http://www.medicinenet.com/mrsa_infection/article.htm Gemmell C.G.,Edwards D.I.,Fraise A.P et al. Guidelines for the prophylaxis and treatment of MRSA infections un the UK. Journal of Antimicrobial Chemotherapy.2006.57:589-608 http://adc.bmj.com/cgi/content/full/89/1/74 http://cme.medscape.com/viewarticle/544583 Bonten M, Wenzel R, Kluytmans J et al. Mupirocin ointment for preventing Staphylococcus aureus infections in nasal carriers. Cochrane Database Syst Rev. 2008 Oct 8;(4):CD006216

References
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Sabel KG, Brandberg A. Treatment of meningitis and septicemia in infancy with a sulphamethoxazole trimethoprim combination. Acta Paediatrica Scandinavica 1975;64:25-32. Tamer MA, Bray JD. Trimethoprim-sulfamethoxazole treatment of multiantibiotic-resistant staphylococcal endocarditis and meningitis. Clin Pediatr 1982;21:125-6. http://findarticles.com/p/articles/mi_m0GVK/is_9_9/ai_108647594/ http://infectious-diseases.jwatch.org/cgi/content/full/2002/621/1 BNF 57. March 2009 Parras F, Guerrero MC, Bouza E et al.Comparative study of mupirocin and oral co-trimoxazole plus topical fusidic acid in eradication of nasal carriage of methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 1995 Jan;39(1):175-9

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