A retrospective analysis of practice patterns in the treatment of methicillin-resistant Staphylococcus aureus skin and soft tissue infections at three Canadian tertiary care centres

BACKGROUND:

Methicillin-resistant Staphylococcus aureus (MRSA) infections are increasingly being encountered and pose an increasing burden to the health care system in Canada.

OBJECTIVE:

To elucidate and characterize the factors influencing the current MRSA treatment patterns in patients with skin and soft tissue infections (SSTIs) before linezolid became available on the Canadian market.

METHODS:

A retrospective study collected demographic, treatment and resource use data on patients hospitalized at one of three geographically distinct tertiary care facilities, where MRSA SSTI treatment was initiated with intravenous (IV) vancomycin. Analysis of opportunities for IV-to-oral switch therapy was based on eligibility criteria.

RESULTS:

Of 89 patients identified over a 43-month period, the mean (±SD) durations of anti-infective treatment and hospitalization were 22.4±21 days and 28.9±20.8 days, respectively. An infected surgical wound was most common, representing 62.9% of infections. The mean duration of vancomycin treatment was 19.5 days and the mean number of 1 g doses received was 29.0±32.9. The majority of patients (55.1%) initiated vancomycin therapy a mean of 5.4±8.9 days after confirmation of MRSA. Of the 70% of patients meeting criteria for IV-to-oral switch therapy, only 10% received oral treatment. The most common reason cited for not switching was lack of an effective oral alternative. Analysis of switch therapy criteria found that IV treatment continued for a mean of 13 days despite the appropriateness of the oral route.

CONCLUSIONS:

Considerable variation exists in treatment patterns for MRSA infections. Improvements in the initiation of therapy and the use of IV-to-oral switch therapy may improve care and reduce the duration of hospitalization for MRSA SSTIs.Key Words: Methicillin-resistant Staphylococcus aureus, Switch therapy, Treatment patterns, VancomycinAntibiotic resistance is of growing importance to health care systems worldwide, and Canada is no exception (1). Due to the serious nature of emerging antibiotic-resistant pathogens and the limited therapeutic options available to treat them, infections caused by these organisms may be associated with increased morbidity and mortality (2-4) compared with those caused by drug-sensitive organisms, and pose an increasing economic burden to health care systems (5). Among the resistant organisms, methicillin-resistant Staphylococcus aureus (MRSA) is increasingly being encountered in Canadian health care facilities (1). Although the first report of an MRSA isolate in Canada was in 1981 (6), only occasional reports followed. In 1995, the Canadian Nosocomial Infection Surveillance Program (CNISP) began following the incidence of MRSA prospectively and reported an increase from 1% of all S aureus isolates in 1995 to 8.1% in 2000 in the health care facilities participating in the CNISP (7). The majority of the increase in MRSA cases has occurred in Ontario and Quebec, followed by British Columbia (7). Although MRSA was initially a hospital-acquired pathogen, it has also recently been recognized as a community-acquired organism (8-11) in Canada, particularly among First Nations peoples.Because MRSA is often resistant to multiple antibiotics, treatment options may be limited. The usual treatment for serious infections caused by MRSA is vancomycin (12). This antibiotic is available only in the intravenous (IV) form for treatment of these types of infections, and it has the potential for greater toxicity and may be less effective than conventional therapy for infections caused by susceptible staphylococci (5). Furthermore, certain organisms have exhibited increasing rates of resistance to vancomycin, which may limit its usefulness. A Passive Reporting Network established within the CNISP identified 1315 cases of vancomycin-resistant enterococci throughout Canada between 1994 and 1998 (13). In addition, cases of vancomycin-intermediate strains of S aureus have been reported recently in Japan, Europe, Hong Kong and the United States (14-16), although no cases have yet been confirmed in Canada.Other than intravenous vancomycin, several oral MRSA treatment alternatives are available including trimethoprim-sulfamethoxazole, alone or in combination with rifampin; doxycycline; fusidic acid in combination with rifampin; or fluoroquinolones alone or in combination with rifampin, dependent on the susceptibility of the strain. Five years of MRSA surveillance in several hospitals across Canada found resistance rates to ciprofloxacin, trimethoprim-sulfamethoxazole, rifampin and fusidic acid to be 89%, 56%, 3% and 3%, respectively (17). Linezolid, an antibacterial agent available in both IV and oral forms, was approved for use in Canada following the completion of the present study and represents a new option for the treatment of Gram-positive infections, including those caused by MRSA.Although vancomycin IV has been identified as the current drug of choice for the treatment of MRSA infections, very little is known regarding the real-life practice patterns of treating physicians across Canada. In an effort to gain an understanding of how MRSA infections are currently being treated, we undertook a retrospective study of vancomycin treatment patterns for MRSA infections in geographically distinct regions across Canada, focusing on infections of the skin and soft tissue (SSTIs). Emphasis was placed on determining MRSA treatment characteristics including antimicrobial use, duration of therapy, length of hospital stay (LOS) and use of home IV care services. In addition, an analysis of IV-to-oral switch therapy patterns was conducted to understand the current level of acceptance of the practice, its potential benefits and the barriers to switch therapy in MRSA SSTIs.     

Quinacrine added to ongoing therapeutic regimens attenuates anticardiolipin antibody production in SLE

The benefit of combining quinacrine (Qn) with hydroxychloroquine (HCQ) in the treatment of systemic lupus erythematosus (SLE) was previously re-evaluated by us. In our current study we observed that, in 11 active SLE patients (SLEDAI score 5-12), the addition of Qn (100 mg/day) to their existing ongoing therapeutic regimens resulted in a significant attenuation of their previously persistent anticardiolipin antibody (aCL) response. This was in comparison with a matched non-Qn treated control group composed of 14 randomly chosen aCL-positive SLE patients with a similar SLEDAI score 6-10. Prior to Qn treatment the therapeutic regimens of 12 months' duration, included in all cases HCQ (400 mg/day), in many cases prednisone (P, 10-20 mg/day) and in some additional cases immunosuppressive drugs. SLEDAI scores and aCL levels were monitored during the entire follow-up period which totaled 24 months in the study group and 15-18 months in the controls. Along with the beneficial effect of the added Qn on SLEDAI scores, aCL disappearance was documented in eight of 11 patients and remained negative during 8-12 months of follow-up (P = 0.004), compared with such a change in only three of 14 non-Qn treated aCL-positive patients (P = 0.18). We conclude that the added Qn treatment to former established therapeutic protocols may eliminate aCL response in SLE patients. Whether this agent's effect is permanent needs further elucidation.     

Importance of delaying balloon angioplasty in patients with unstable angina pectoris

Angioplasty in patients with unstable coronary artery disease is associated with higher complication rates compared with patients with stable disease. In this report we describe our results from a group of patients with unstable disease (unstable angina pectoris and postmyocardial infarction) where a strategy of delaying angioplasty for >5 days after admission was undertaken. Included are 2069 consecutive patients: 1197 treated for stable angina pectoris and 872 treated during admission for unstable angina or myocardial infarction. There was no difference between the two groups in angioplasty success (92.1% stable, 92.3% unstable), failure to dilate without complication (6.4% stable, 6.1 % unstable), or in the rate of major complications: death (0.5% stable, 1.1% unstable), Q-wave myocardial infarction (0.9% stable, 1.1% unstable), and emergency coronary artery bypass (0.6% stable, 0.3% unstable). The duration of hospitalization following angioplasty was longer in the unstable group (5.6 ± 8.1 days vs. 4.2 ± 4.1 days; p < 0.001) because of longer duration of hep-arin infusion. There was no difference between groups in minor complications such as groin hematoma and pseudoa-neurysm, renal failure, or infections. It was concluded that delaying angioplasty in unstable patients for > 5 days after admission is a safe and effective therapeutic strategy for this group of patients. The need for prolonged heparin infusion after angioplasty is increased in unstable patients and thus the duration of hospitalization after the procedure is longer.     

Huge left atrial thrombus and valve degeneration in a patient with a bioprosthetic, porcine, mitral valve

A 43 year old man with a Hancock porcine bioprosthetic valve in the mitral position developed a huge thrombus filling the entire left atrium and chronic degeneration of the bioprosthetic mitral valve. The effective valve orifice was less than 2 mm. These severe findings leading to the patient's death remained undetected while he was alive. This case illustrates the great need for a serial phonoechocardiographic studies in all patients with prosthetic valves.     

Microscopic polyangiitis presenting as idiopathic pulmonary fibrosis: is anti-neutrophilic cytoplasmic antibody testing indicated?

We report a 55-year old woman with microscopic polyangiitis who presented with idiopathic pulmonary fibrosis and 1 year later developed hematuria and proteinuria. She had a high serum level of perinuclear anti-neutrophilic cytoplasmic antibodies. Renal angiogram was normal. The diagnosis of microscopic polyangiitis was confirmed by renal biopsy, which showed pauci-immune crescentic glomerulonephritis. The patient received immunosuppressive therapy and improved markedly. Consideration of small vessel vasculitis is important in the differential diagnosis of idiopathic pulmonary fibrosis.     

Spontaneous regression of congenital leukaemia with an 8;16 translocation

Congenital leukaemia (CL) is a rare disorder that presents with extramedullary infiltrates and a myeloid phenotype. CL can progress rapidly without adequate treatment, but, paradoxically, may also remit spontaneously. Because of the significant toxicity involved in delivering chemotherapy to newborns, it is important to identify those newborns who may not require treatment. We describe an infant who presented at 1 week of age with congenital myeloid leukaemia. Cytogenetic analysis revealed a t(8;16)(q11;p13) translocation. The infant's leukaemia underwent a spontaneous regression. This case further confirms the possibility of spontaneous remission in congenital leukaemia. Moreover, it suggests that the presence of a clonal cytogenetic aberration does not preclude the possibility of a spontaneous regression in CL.