Guidelines of the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections: As Applied to Oral and Maxillofacial Clinical Practice

Abstract

Purpose

The purpose of this paper was to undertake a systematic review of literature on methicillin-resistant Staphylococcus aureus infections in oral and maxillofacial online data-bases and discuss the Infectious Diseases Society of America (IDSA) guidelines and its applications in maxillofacial clinical practice.

Materials and Methods

The available literature in oral and maxillofacial online databases was searched. The only inclusion criterion was to review published reports, abstracts and retrospective studies with emphasis on the treatment of clinical cases with methicillin-resistant S. aureus infections. Clinical Practice Guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant S. aureus infections in adults and children was reviewed and included in the study.

Results

Out of 18 articles found with the search terms “Methicillin-resistant S. aureus” and “MRSA” in the online databases 12 articles met the inclusion criteria for this study. The relevant data was extracted and tabulated.

Conclusions

Conclusions were drawn and discussed based on the reviewed maxillofacial literature and the Guidelines by the IDSA.

Introduction

Staphylococcus aureus has been long associated with a wide spectrum of infectious diseases ranging from skin infections including impetigo, furuncles, folliculitis, carbuncles, abscesses, wound infections to more serious infections such as pneumonia, meningitis, osteomyelitis, endocarditis, toxic shock syndrome, staphylococcal bacteremia, and sepsis. This Gram-positive micro-organism has been frequently reported to have acquired resistance to antimicrobials [1]. Methicillin-resistant Staphylococcus aureus (MRSA) infections were first described after the introduction of methicillin in 1959 [2]. S. aureus and MRSA have been reported to colonize as commensals in humans without causing infection. Over the past few years, MRSA has emerged as one of the most dreaded nosocomial pathogens, responsible for multiple institutional outbreaks [1]. The oral and nasal cavities are regions that commonly harbor MRSA [3]. Recent reports of MRSA strains circulating at the community level are on the rise [4, 5]. It has been emphasised in a retrospective study by Minoru Miyake et al. [6] that elimination of MRSA is of critical importance in oral and maxillofacial surgical practice, as control is very difficult once infection of an oral tumor or oral wound with MRSA is established. Recently, Infectious Diseases Society of America (IDSA) has released its first guidelines, for the treatment of increasingly common MRSA infections [7]. The presented study reviews the available literature in oral and maxillofacial online data-bases and discusses the IDSA guidelines and its application in maxillofacial clinical practice.

Materials and Methods

A systematic search of the literature was carried out to identify eligible articles. The investigators searched the literature using the terms ‘‘methicillin-resistant Staphylococcus aureus’’ and ‘‘MRSA’’ in the online databases of the Journal of Oral and Maxillofacial Surgery; International Journal of Oral and Maxillofacial Surgery; British Journal of Oral and Maxillofacial Surgery; Oral Surgery, Oral Medicine, Oral Pathology’ Oral Radiology and Endodontics. The only inclusion criterion was to review published reports, abstracts and retrospective studies with emphasis on the treatment of clinical cases with MRSA infections between 2002 and 2010. Clinical Practice Guidelines by the IDSA for the Treatment of MRSA Infections in Adults and Children was reviewed and included in the study. As this study involved only the online database search and review of published data, it was exempt from Institutional Ethics Committee (IEC) approval.

Results

Out of 18 articles found with the search terms ‘‘methicillin-resistant Staphylococcus aureus’’ and ‘‘MRSA’’ in the online databases 12 articles met the inclusion criteria for this study. The relevant data was extracted and tabulated (Table 1). Conclusions were drawn and discussed based on the reviewed maxillofacial literature and the Guidelines by the IDSA.

Table 1.

Literature published between 2002 to 2010 in the data-bases searched for reports on MRSA in maxillofacial literature

Sl. no.	Author	Year	Number of patients with MRSA	Infection site/type of surgery	Antibiotics used	Maximum duration of antibiotic usage	Comments
1	Avery [18]	2002	2	Infection of radial donor site	Vancomycin (IV), teicoplanin (IV)	1 week	Emphasis on wound debridement
2	Cohen [1]	2003	1	Osteomyelitis maxilla	Vancomycin (IV), oral ciprofloxacin	12 days (IV) 2 weeks (oral)	First reported case of osteomyelitis of the maxilla in a healthy nurse
3	Yoshinari Morimoto [3]	2005	2	Mandibular resection with fibula reconstruction	Vancomycin (IV), ceftazidime (IV)	1 week (IV) 4 weeks (Beads)	Intravenous antibiotics cannot sufficiently penetrate the target tissue because of limited blood supply to the failed graft, local drug delivery is beneficial
4	Carter [4]	2005	11	Community Acquired MRSA Facial Abscesses	Vancomycin (IV) was found sensitive in all cases	14 days	Facial abscesses caused by MRSA responds well to vancomycin
5	Avery [8]	2006	17	Free flap reconstructions of defects after excision of lesions in the head and neck	Cefuroxime (IV), metronidazole (IV)	5 days	The median length of hospital admission was greater for patients that acquired MRSA
6	Bruno [5]	2007	1	Lip Abscess progressing to necrotizing pneumonia	Vancomycin, piperacillin/tazobatam, and gentamycin (IV)	Patient expired	Community-acquired MRSA infection with fatal necrotizing pneumonia from lip abscess
7	Minoru Miyake [6]	2007	518	Oral cancer	Mupirocin ointment	–	Mupirocin nasal ointment in conjunction with comprehensive hygienic care provides an effective measure for preventing MRSA in oral cancer patients at risk of the infection
8	Rogers [9]	2008	97	All patients with oral and oropharyngeal squamous cell carcinoma: primary sites after surgery, sputum, nose tracheostomy, drain site, blood culture, gastrostomy, groin, urine, intravenous cannula, Eye, oral/pharyngeal	–	–	MRSA infection is more prevalent among oncology patients particularly those requiring free tissue transfer
9	Ward [12]	2008	1	Sinus lift bone grafting and dental implants	Vancomycin (IV) and levofloxacin	6-week	MRSA sinusitis
10	Aysegul Mine Tuzuner-Oncul [10]	2009	1	Osteomyelitis mandible	Clindamycin (IV), local rifampicin irrigation	13 days	Osteomyelitis following parasymphyseal mandible fracture
11	Burduk [11]	2010	1	Osteomyelitis maxilla	Ceftazidime (IV), metronidazole (IV), oral clarithromycin	3 weeks (IV) 2 weeks (oral)	Healthy young man with osteomyelitis of the maxilla caused by Methicillin resistant S epidermidis (MRSE)
12	Zhang [19]	2010	1	Cervical necrotizing fasciitis	Vancomycin (IV)	6 weeks	Patient developed mediastinitis

Discussion

MRSA is a common nosocomial infection that worsens prognosis, increase the length of the hospital stay and is a great financial burden on the health care systems world-wide. It was the need of the day to have clear guidelines on management of infections complicated by the presence of MRSA. The 13 member MRSA guidelines panel was convened by the IDSA Standards and Practice Guidelines Committee in 2007 to develop evidence-based guidelines for managing patients with MRSA infections, the outcome of which forms a framework for clinicians to handle MRSA infections in a more systematic manner [7]. The guidelines are based on the review and analysis of data published from 1961 to 2010 in PUBMED, abstracts, national meetings, randomized clinical trials, observational studies, case series and the opinion of the expert panel.

Although the published reports of MRSA infection in the searched data bases for this study remained low, a clear understanding on managing such infections when encountered is essential (Fig. 1). In maxillofacial surgical practice, the most common group of patients to have MRSA infections were cancer patients treated with primary resections and requiring reconstruction with free flaps [8, 9]. A few cases of osteomyelitis of jaws complicated with MRSA are reported [1, 10, 11]. Bruno et al. [5] have reported a case of community acquired MRSA lip infection that progressed to necrotizing pneumonia and patient expired inspite of administration of appropriate antimicrobials and intensive care. Reports of MRSA infections following dento-alveolar procedures like dental implants and sinus lift is a warning signal warranting strict asepsis in all maxillofacial and dental setups [12].

Fig. 1.

Published articles in the data-bases searched for reports on MRSA in Maxillofacial literature. (X axis: year; Y axis: number of published reports)

According to the recommendations of Liu et al. [7] in the IDSA guidelines on management of MRSA infections, simple abscesses or boils would require incision and drainage alone, and antibiotic therapy is not needed. Antibiotic therapy is recommended for abscesses associated with the conditions summarized in Table 2. Among skin and soft tissue infections with current evidence of knowledge, purulent cellulitis should be treated empirically for MRSA and nonpurulent cellulitis should be treated empirically for β-hemolytic streptococci. Culture and sensitivity tests of appropriate biological samples should be sought. Based on the recommendations, oral antibiotics for community acquired MRSA are clindamycin, trimethoprim-sulfamethoxazole, a tetracycline (doxycycline/minocycline), or linezolid for a period of 5–10 days individualized on the basis of the patient’s clinical response. Patients requiring hospitalization for skin and soft tissue infections should receive a thorough surgical debridement, broad-spectrum antibiotics, and empiric MRSA treatment that includes intravenous vancomycin, oral or intravenous linezolid, daptomycin, telavancin, or clindamycin for a period of 7–14 days (Table 3).

Table 2.

Conditions requiring antibiotic therapy for abscesses [7]

Antibiotic therapy is recommended for abscesses associated with the following conditions
(1) Severe or extensive disease or rapid progression in presence of associated cellulitis
(2) Signs and symptoms of systemic illness
(3) Associated comorbidities or immunosuppression (diabetes, HIV)
(4) Abscess in area difficult to drain completely (e.g., face, hand, genitalia)
(5) Associated septic phlebitis
(6) Lack of response to incision and drainage alone
(7) Extremes of age

Table 3.

Antibiotics for patients requiring hospitalization for skin and soft tissue infections [7]

Drug	Dosage
Vancomycin	15–20 mg/kg/dose IV every 8–12 h, not to exceed 2 g per dose
Linezolid	600 mg PO/IV twice daily
Daptomycin	4 mg/kg/dose IV once daily
Telavancin	10 mg/kg/dose IV once daily
Clindamycin	600 mg IV/PO three times a day

Teeth bearing maxillofacial skeleton is commonly affected by osteomyelitis, which is one of the feared condition by most maxillofacial surgeons to treat [13]. Septic arthritis of the temporomandibular joint is a rare condition with high morbidity [14]. With the advent of various TMJ prosthesis, a vast number of patients are requiring total joint reconstruction are benefited. Although TMJ total joint prostheses can become infected, as any other prosthetic device in the human system [15]. According to the recommendations [7], for the management of MRSA bone and joint infections (osteomyelitis, septic arthritis and infections involving joint prosthesis) surgical debridement and drainage should be given emphasis and remain the mainstay of the treatment. Antibiotics for parenteral administration include vancomycin and daptomycin, trimethoprim-sulfamethoxazole in combination with rifampin, linezolid, clindamycin and refampin in combination to any of the previously mentioned antimicrobials. ESR and CRP levels are useful investigations to guide the clinicians to assess response to the therapy. Recommendations for choice of the antimicrobial, dosage and the duration for MRSA bone and joint infections is summarised in Table 4.

Table 4.

Antibiotic recommendations for MRSA bone and joint infections [7]

MRSA bone and joint infections	Recommended antibiotics	Duration	Comments
Osteomyelitis	IV Vancomycin 15–20 mg/kg/dose IV every 8–12 h, not to exceed 2 g per dose and daptomycin 6 mg/kg/dose IV once daily Trimethoprim-sulfamethoxazole 4 mg/kg/dose twice daily with rifampin 600 mg once daily Linezolid 600 mg twice daily Clindamycin 600 mg every 8 hourly	Minimum 8-week course	Importance to be given to surgical debridement and drainage
Septic Arthritis	Same as osteomyelitis	3–4-week course	Drainage/debridement of the joint space is mandatory
Prosthetic joint infections	Parenteral therapy same as osteomyelitis plus rifampin 600 mg daily or 300–450 mg PO twice daily	2 weeks parenteral therapy followed by oral antibiotics	Debridement, consider device removal. Initial parenteral therapy plus rifampin followed by prolonged oral therapy is recommended Long-term oral antibiotics (e.g. fluoroquinolones) to be given in conjunction with rifampin to prevent emergence of fluoroquinolone resistance.

It is not infrequent in maxillofacial surgical practice to encounter patients who are at a risk of developing bacteremia [16] and infective endocarditis [17]. Although the treatment and management of patients for MRSA bacteremia and infective endocarditis is beyond the scope of maxillofacial surgical practice, an insight in the drugs used for their management remains beneficial as many such patients may have associated MRSA soft or hard tissue facial infections. Vancomycin or daptomycin remains the recommended antimicrobials for uncomplicated bacteremia for at least 2 weeks where as complicated bacteremias need treatment for 4–6, and 6 weeks treatment for MRSA infective endocarditis [7].

Current evidence clearly demonstrates that vancomycin remains the drug of choice for MRSA infections. According to IDSA guidelines [7], in adults the dose of IV vancomycin is 15–20 mg/kg/dose every 8–12 h and should not exceed 2 g per dose. In children administration of 15 mg/kg/dose every 6 h is recommended. Determining “trough vancomycin concentration” is the most accurate and practical method to guide vancomycin dosing. Trough monitoring is recommended to achieve target concentrations of 15–20 μg/mL in patients with serious MRSA infections. In cases with skin and soft tissue infections, the vancomycin dose of 1 g every 12 h should suffice and trough levels monitoring is not necessary.

Treatment of MRSA infections is challenging. Prevention remains better than cure as MRSA infections once established require herculean efforts to attain resolution. The importance of strict adherence to sterilisation and asepsis protocols, good wound care with clean dry bandages, personal and environmental hygiene, surveillance cultures, decolonization and scientifically justified use of antimicrobial therapy should never be under-estimated.

Conclusions

IDSA guidelines have laid a framework for the management of patients with MRSA infections. Although published reports lack in number, maxillofacial MRSA infections are on the rise. Vancomycin remains the drug of choice for MRSA infections with adults dosage of IV vancomycin of 15–20 mg/kg/dose every 8–12 h which should not exceed 2 g/dose. For paediatric group dosage of 15 mg/kg/dose every 6 h is recommended.