ORIGINAL ARTICLE Retrospective study of outcome in patients treated for Staphy 1ococcus aureus b ac teremia Pauline E. Gosdenl, Barnaby C. Reeves2,]ames R. S. Osborne3, Andrew Turner' and Michael R. Millarl 'Department of mcrobiology, 2Research and Development Support Unit, and 3Department of Pathology, University of Bristol, Bristol Royal Infirmary, United Bristol Healthcare Trust, Bristol, UK Objective: To investigate whether a change in current treatment practice for Staphylococcus aureus bacteremia from flucloxacillin and aminoglycoside to flucloxacillin and fusidic acid was associated with any changes in outcome. Methods: A retrospective analysis was carried out of 316 episodes of S. aureus bacteremia diagnosed and treated in a tertiary hospital complex between 1983 and 1993. Outcomes considered were (1) death related to the infection and (2) relapse following cessation of antibiotic therapy. Results: Mortality related to infection, which occurred in 24% of patients, was unrelated to treatment with the combination of flucloxacillin and fusidic acid; however, increasing age was a significant risk factor (OR per decade = 1.35, 95% CI = 1.1&1.55), and increasing duration of treatment (OR per week of treatment = 0.63,95% CI = 0.52-0.77), use of flucloxacillin (OR= 0.30,95% CI = 0.14-0.64). presence of an intravascular device (OR= 0.39,95% CI = 0.20-0.78) and presence of a skin lesion (OR = 0.51, 95% CI = 0.26-0.99) were significant protective factors. The only factor significantly related to relapse, which occurred in 11% of patients, was treatment with the combination of flucloxacillin and fusidic acid (OR = 0.32, 95% CI = 0.12-0.85). There was approximately a 70% reduction in the risk of relapse if this combination was used. Conclusions: This retrospective analysis suggests a clinically important protective effect of fusidic acid against relapse in patients with S. aureus bacteremia. Although the results were adjusted for potential confounding factors, the possibility of bias remains. There is a need for a prospective randomized trial to evaluate the effectiveness of flucloxacillin and fusidic acid for treating S. aureus bacteremia. Key words: Staphylococcus aureus, bacteremia, fusidic acid, antibiotics INTRODUCTION and the presence of foreign bodies, although infection may arise without a predisposing factor. Infection with Staphylococcus aureus is the most fiequent cause of S. aureus is frequently associated with bacteremia and bacteremia due to Gram-positive bacteria and the metastatic disease [6-81. commonest cause of wound infection in the UK. The Conflicting observations have resulted in un- reported mortality associated with S. aureus bacteremia certainty concerning the optimum duration of anti- ranges fiom 21% to 43% [l-51. Factors that preckspose biotic therapy for bacteremia caused by S. aureus [8]. to infection with S. aureus include breaches in the skin Many believe that all patients with S. aureus bacteremia should be treated with a 4-6 week course of intra- venous antibiotics [9,10] in order to prevent serious sequelae such as endocarditis. Recently, some authors Corresponding author and reprint requests: have suggested that shorter courses of therapy for Pauline E. Gosden, Department of Microbiology, Level 8, catheter-related bacteremia and uncomplicated right- Bristol Royal Infirmary, United Bristol Healthcare Trust, sided endocarditis in intravenous drug users would be Marlborough Street, Bristol, BS2 8HW. UK adequate [ll-161, whereas others have maintained that Tel: 0117-9282567 Fax: 01 17-9299162 short-course therapy results in unacceptable rates of Accepted 17 August 1996 complication and relapse [17,18]. 32 Gosden et al: Outcome in patients treated for Staph. aureus bacteremia 33 Fusidic acid is frequently used in the UK but rarely micin, fusidic acid and erythromycin [22]. Suscepti- in the USA [19,20]. Use of fusidic acid was not bility to methicillin was determined with a paper emphasized in the laboratory recommendations for strip containing 25 pg methicillin, on blood agar and the treatment of S. aureus bacteremia in the United mannitol salt plates incubated at 30°C and 37OC Bristol Hospital Trust (UBHT) complex of hospitals respectively. until 1991, when a laboratory recommendation of Demographic data recorded from the notes flucloxacillin and fusidic acid, given as the sodium salt included date of birth, sex, age at time of the positive for 4 weeks, was introduced. blood culture, and whether infection was acquired in At dus time it was felt that an antibiotic combina- the community or the hospital. Associated condtions tion including hsidc acid would, because of its better whch might influence outcome, such as malignancy, tissue penetration, offer benefit in terms of outcome for diabetes mellitus, rheumatoid arthritis, cardiac disease, the patient over a combination involving an amino- intravenous drug use and immunosuppression (asplenia, glycoside. We report a review of the outcome of steroid therapy, neutropenia, cytotoxic therapy), were patients treated for S. aureus bacteremia in the UBHT documented. Possible risk factors for infection, such between 1983 and 1993 with particular emphasis on as bone fracture, skin lesions, transcutaneous foreign the impact of the use of fusidic acid. bodies, operation within the previous year, prosthetic joints, bone screws and nails and prosthetic heart valves, were also recorded. Microbiological data included the PATIENTS AND METHODS date of the positive blood culture, and whether S. aureus was isolated &om the respiratory tract, urinary tract, Data were collected by a retrospective review of case skin/wound lesions or intravascular line tips. Treatment records for patients diagnosed and treated for S. aureus information recorded included antibiotics and their bacteremia between January 1983 and December 1993 duration of use. in the UBHT hospital complex. These hospitals form Information about the outcome of treatment a large teaching hospital unit with regional specialities included the date of death, whether death was related including cardiac surgery, oncology services and neo- to infection and whether a relapse occurred. The natal intensive care. In 1993, 54 000 inpatients were infection was classified as community acquired if the treated in the UBHT. In addtion to drawing patients blood cultures had been collected within 48 h of from the central and south Bristol areas, it also acts as hospital admission &om the community and as hospital a referral centre for the southwest of England. The acquired in all other cases. A relapse was said to have Bristol catchment population was 361 000 in 1983, occurred if a patient developed a new suppurative rising to 370 000 in 1991 (estimates based on Office complication or blood culture with S. aureus within 5 of Population and Censuses Surveys 1993 mid-year years following cessation of antibiotic therapy. In 92% population). of cases, relapse occurred within 10 months. Phage The UBHT cases were identified by searching typing was documented in only three cases and showed laboratory records of blood cultures, collected between identical phage types for both isolates. Antibiotic January 1983 and December 1993, from which S. susceptibility profiles were identical in all cases with the aureus had been grown. Patients with no clinical diag- exception of one. Death was considered to be related nosis of infection and who were not treated for to infection (DRI) if the death resulted from acute infection, and those with polymicrobial bacteremia sepsis syndrome or a complication of S. aureus without corroborating clinical or laboratory evidence bacteremia, such as endocarditis. Post-mortem data of S. aureus infection, were excluded. were used when available. The method of obtaining blood cultures changed Information recorded fi-om the notes was trans- in July 1988. Prior to 1988, blood cultures were ferred to a database. Descriptive statistics for demo- performed by inoculation of 5-10 d of aseptically graphic and relevant clinical data were calculated, drawn blood into brain-heart infusion (Oxoid CM including the proportions of patients receiving fusidic 225, Unipath Ltd, Basingstoke) and thioglycollate acid and the proportion experiencing the outcomes of broths. Broth cultures were subcultured onto solid interest, in each year. The effects of various clinical media afker 2 and 7 days. After July 1988 a commercial factors and treatment combinations on each outcome automated blood culture system was adopted (Bactec were then investigated in more detail by statistical 660, Becton Dickinson UK Ltd, Oxford). Identifica- modeling using multiple logistic regression, allowing tion of S. aureus was carried out by standard methods estimates of odds ratios (ORs) for different factors to [21]. Antibiotic susceptibility was determined by Stokes' be obtained with and without adjustment for possible method for the following antibiotics: penicillin, genta- confounding variables. 34 Clinical Microbiology and Infection, Volume 3 Number 1, February 1997 RESULTS The number of cases in each year ranged from 15 to 45. There appeared to be an increase in the number The total number of patients for whom blood cultures of cases occurring over time, paralleling the increase in were requested &om 1985 to 1993 was 66 447 and total requests and positive blood cultures, despite an requests showed an upwards trend from 6523 in 1985 essentially constant catchment population (x2=23.65, to 9193 in 1993. Data for total requests were unobtain- degrees of fieedom 10, p<O.Ol; linear regression of able for 1983 and 1984, as laboratory computerization number of cases against time gave a p coefficient for was not implemented until 1985. The annual total of each year of 1.95 cases, p=0.004). These trends may all patients with positive blood cultures rose from 437 have been due to better detection of cases, better use in 1985 to 739 in 1993, but the proportion positive for of the laboratory or a real increase in numbers of cases. S. aureus remained constant at approximately 11% of The median age was 51.6 years with an inter- the total. Between January 1983 and December 1993, quartile range (41-43) of 20.8-68.5 years.