Methicillin-sensitive S. Aureus Bacteremia Research Articles

793. Rifabutin Use in Staphylococcal Prosthetic Material Infections: A Case Series

BackgroundBacterial biofilm formation is of clinical concern among patients with staphylococcal infections involving prosthetic material. While rifampin has in-vitro, animal and clinical data to support its adjunctive role in these types of infections, its potent induction of multiple cytochrome P450 enzymes and P-glycoprotein transport system proteins can pose significant drug-drug interactions. Rifabutin has comparable in-vitro anti-staphylococcal activity but less drug-drug interaction potential than rifampin. However, minimal clinical data exists to support rifabutin use as adjunctive treatment of prosthetic infections.MethodsThis case series describes 7 patients who received adjunctive rifabutin for staphylococcal prosthetic material infections between February 2018 and January 2021 at Massachusetts General Hospital. The primary outcome of infection recurrence was defined as need for surgical intervention for suspected or proven recurrence infection within 6 months after starting rifabutin therapy. Incidence of adverse effects was the main secondary outcome.ResultsMost patients (6/7) had methicillin-sensitive S. aureus (MSSA) and one patient had S. epidermidis infection. Three patients had spinal fusion hardware infection, one patient had hardware-associated spinal osteomyelitis/ diskitis with epidural abscess, two patients had prosthetic joint infection, and one patient had MSSA bacteremia with left ventricular assistance device involvement. All patients except one underwent surgical management prior to starting rifabutin. Infection recurrence was noted in one of seven patients who required surgical washout. Adverse events were uncommon (n=1 treatment-related nausea, n=1 leukopenia).ConclusionThis small case series suggests favorable outcomes with use of rifabutin instead of rifampin for staphylococcal infections with prosthetic material involvement.Disclosures Sandra B. Nelson, MD, UpToDate (Other Financial or Material Support, author)

Staphylococcus Aureus Bacteremia Due to Central Venous Catheter Infection: A Clinical Comparison of Infections Caused by Methicillin-Resistant and Methicillin-Susceptible Strains.

Objectives: Staphylococcus aureus bacteremia has a mortality rate of 20-40% and is mainly caused by central venous catheter (CVC) infection. We aimed to investigate differences between patients with methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA) bacteremia due to CVC infection.Methods: This retrospective study, of data collected between August 2004 and March 2016 at a single Tokyo hospital, compared the clinical background characteristics, complications, and 60-day mortality rates with positive peripheral blood cultures and positive semiquantitative cultures. MRSA carrier is defined as those with a history of MRSA detection by skin, urine, or sputum culture.Results: The median ages for the 17 MRSA and 19 MSSA patients were 72 and 55 years, respectively (P < 0.01). The occurrences of baseline disease (MRSA vs. MSSA) were 59% vs. 16% (P = 0.01), respectively, while those of complications, including septic shock, were 48% vs. 16% (P = 0.07), respectively. Catheter placement duration, time from fever onset to CVC removal, and time from fever onset to antimicrobial therapy initiation were similar in both groups. Sixty-day mortality rates were 35% and 5.3% (P = 0.04) in the MRSA and MSSA groups, respectively.Conclusion: MRSA carriers and older patients were at higher risks of CVC infection than MSSA bacteremia patients. Patients with MRSA bacteremia had higher septic shock and 60-day mortality rates despite appropriate antimicrobial therapy.

282. Epidemiological Evaluation of Methicillin-Resistant Staphylococcus aureus (MRSA) and Methicillin-Susceptible Staphylococcus aureus (MSSA) Bacteremia: A Comprehensive Cancer Center’s 10-Year Experience

BackgroundCoagulase-positive Staphylococcus aureus bacteremia among cancer patients carries significant morbidity and mortality. This study aims to compare the risk factors and clinical outcomes among cancer patients diagnosed with bloodstream infection (BSI) with methicillin-sensitive S. aureus (MSSA) or methicillin-resistant S. aureus (MRSA).MethodsWe performed a retrospective cohort study on all patients diagnosed with an active solid tumor or hematologic cancer with positive blood culture for S. aureus from January 2009 to May 2019. We collected data on demographics, comorbidities, malignancy type, venous access, neutropenia status, echocardiogram results, treatment (tx) duration, antibiotics usage pre/post culture, hospital LOS, infection severity, and 7-day and 30-day mortality. We used the Chi-square test to analyze categorical variables, t-test to analyze continuous variables, and the Kaplan-Meier survival curve and multivariate regression to analyze mortality.ResultsTwo hundred eighty-three cases with malignancies and S. aureus BSIs were reviewed, and 168 were identified with BSIs for MRSA or MSSA during the ten years. The mean age for MRSA cases was 73.1 (±13.7) and 70.1 (± 14.6) for MSSA; male patients were most of the sex (P < 0.01). MRSA and MSSA bacteremia presented equally in hematologic malignancies, while MSSA was observed more in skin cancer than MRSA. Cancers that obstruct GU tracts may be associated with MRSA and MSSA from urine source as both were overrepresented in patients with bladder and rectal cancer. In most patients, the CVC was promptly removed and appropriate antibiotics were given promptly within 1 hour of the positive blood culture. For patients who underwent echocardiogram, most had a negative result in both groups. There was no significant difference for seven and 30-day mortality between the two groups. The mean hospital LOS was longer for MRSA cases (10.5 ± 13.5) versus MSSA cases (4.88 ± 9.1), (P < 0.01). Figures 1 & 2. Kaplan-Meier Survival Curve Comparing 7 and 30-day Mortality of Cancer Patients with MRSA vs MSSA BSI Figure 3 & 4. Distribution of Cancer Types for MRSA (n=84) and MSSA (n=84) BSI ConclusionEndocarditis with either MRSA or MSSA BSI is not a prominent finding among cancer patients at our institution. Given the extensive usage of CVCs and devices in patients with malignancies, prompt removal and antibiotic administration are essential to reduce morbidity; even then, the LOS for MRSA BSI remains longer than MSSA BSI.Disclosures All Authors: No reported disclosures

1809. Improved Vancomycin Utilization With Rapidly Available Xpert MRSA/SA BC PCR and Microbiologist Case Review

Background Staphylococcus aureus bloodstream infections are life threatening, and are empirically treated with vancomycin. Our objective was to assess the impact of a rapidly available PCR for methicillin-resistant S. aureus (MRSA) on the amount and duration of vancomycin use in methicillin-sensitive S. aureus (MSSA) bloodstream infections.MethodsIn October 2016, the Xpert® MRSA/SA BC assay, a PCR to detect MRSA from blood cultures, was implemented at Kelowna General Hospital. MRSA PCR was performed on one bottle per episode for blood cultures with Gram-positive cocci in clusters in at least 3/4 bottles. The medical microbiologist promptly phoned the most responsible physician with results to streamline antibiotics. All episodes of MSSA bacteremia between January 1, 2013 to September 30, 2016 (pre-implementation group) and November 1, 2016 to January 31, 2018 (post-implementation group), were matched to corresponding vancomycin defined daily doses (DDD) and days of therapy (DOT) in pharmacy records. Patients with ≥5 DOTs were excluded if they had allergies to β-lactams, polymicrobial infections with organisms requiring vancomycin, were on hemodialysis (vancomycin convenience dosing), or were transferred from another hospital with known S. aureus bacteremia. Mean vancomycin DDDs and DOTs, and the proportion of patients receiving at least one dose of vancomycin, were compared between groups. Categorical variables were analyzed using the chi-square test, while continuous variables were compared using the t-test.ResultsIn the pre-PCR group, 383 episodes of MSSA bacteremia were identified, with 21 excluded. In the post-PCR group, 100 episodes were found, with 3 excluded.Significantly more patients received at least one dose of vancomycin in the pre-PCR (70.2%) compared with the post-PCR group (54.6%) (P < 0.01). The mean DDD was 1.5 in the post-PCR group, less than the pre-PCR group at 2.8 (P < 0.01). The mean DOT also decreased, with the post-PCR group receiving less vancomycin (1.6 days) compared with the pre-PCR group (2.5 days) (P < 0.01).ConclusionRapidly available MRSA PCR for S. aureus bloodstream infection coupled with antimicrobial stewardship performed by medical microbiologists led to a significant decrease in vancomycin use.Disclosures All authors: No reported disclosures.

Factors associated with 12 week case-fatality in Staphylococcus aureus bacteraemia: a prospective cohort study

Staphylococcus aureus bacteraemia (SAB) is a frequent and deadly disease. Given the lack of a randomized trial, optimal first-line antibiotic treatment is still debated. Our aim was to identify prognostic factors in SAB patients and to analyse the impact of first-line antibiotics. The VIRSTA prospective cohort study was conducted in eight tertiary care centres in France. Consecutive incident adults in whom a blood culture drawn in participating centres grew S. aureus between April 2009 and October 2011 were prospectively followed for 12 weeks. Factors associated with 12-week case-fatality were identified by multivariate logistic regression. We enrolled 2091 patients and analysed survival in 1972 (median age 67.8 years, interquartile range 55.5–78.9; females 692/1972, 35.1%). SAB was nosocomial or healthcare-related in 1372/1972 (69.6%) of cases and the primary focus was unknown in 414/1972 (21.0%) of cases. Week 12 case-fatality rate was 671/1972 (34.0%). The main independent prognostic factors on multivariate analysis were age (adjusted OR by 10-year increment 1.56; 95% CI 1.44–1.69), septic shock (OR 5.11; 95% CI 3.84–6.80), metastatic cancer (OR 4.28; 95% CI 2.88–6.38), and unknown primary focus (OR 2.62; 95% CI 2.02–3.41). In the 1538 patients with methicillin-sensitive S. aureus (MSSA) bacteraemia, first-line empiric antistaphylococcal penicillins (OR 0.40; 95% CI 0.17–0.95) and vancomycin (OR 0.37; 95% CI 0.17–0.83), alone or combined with an aminoglycoside, were associated with better outcome compared with other antibiotics. There are few modifiable prognostic factors for SAB. Initiating empiric antibiotics with antistaphylococcal penicillins or vancomycin may be associated with better outcome in MSSA bacteraemia.

Long term molecular epidemiology of methicillin-susceptible Staphylococcus aureus bacteremia isolates in Sweden.

Staphylococcus aureus is one of the major pathogens that causes bacteremia; therefore, it is important to understand the long-term molecular epidemiology of S. aureus bacteremia infections. In particular, little is known about the population structure of methicillin-sensitive S. aureus (MSSA) compared to that of methicillin-resistant S. aureus. We investigated potential changes in the MSSA molecular epidemiology in Örebro County, Sweden, from 1980 through 2010. 400 MSSA bacteremia isolates, the first 100 isolated each decade from 1980 through 2010, were retrospectively identified and analyzed regarding assignment to clonal complexes (CCs), presence of virulence genes and antibiotic resistant determinants with DNA microarray-based genotyping. 24 different CCs were identified. Most isolates (80%) belonged to 6 predominant lineages. Of those, the number of isolates assigned to CC5 and CC15 increased, and those assigned to CC8, CC25, and CC30 decreased. The most prevalent clone, CC45, did not show a significant change in prevalence during the study period. A change in prevalence was observed for some of the virulence genes, mainly attributed with their association to certain CCs. With the exception of the common blaZ gene (encoding penicillinase), antibiotic resistance genes were only sporadically detected. In conclusion, the MSSA population structure was genetically diverse. We observed decadal changes in assignments to five predominant clones, and corresponding changes in the prevalence of some virulence genes linked to CC affiliation. In light of the restrictive antibiotics prescriptions and extensive infection control procedures in Sweden, antibiotic resistance genes were rarely detected and their prevalence unaffected during the study period.

New therapeutic approach for the treatment for staphylococcal bacteremia and sepsis

Introduction. Staphylococcal bacteremia is an early and dangerous manifestation of infection, it indicates to the presence of the source of infection in the bloodstream or the dissemination ofgerms from otherfoci, is the cause of high mortality rate. In that the approaches to the treatment for bacteremia/sepsis caused by S.aureus, have surprisingly low conclusiveness and require the optimization of antibiotic therapy, duration of treatment, criteria for cure. The aim of this study was to perform the systematic analysis of the current literature devoted to the problem of antibiotic treatment for staphylococcal infection, primarily followed by bacteremia and sepsis. Objectives of the study: the detection of the problem factors having the negative impact on the effectiveness of the antibiotic treatment of severe staphylococcal infections followed by bacteremia, and prospects for the use of new antibiotics. For the solution of the designated objectives in the scientific medical databases Medscape and Pubmed there was performed the search for the publications on subject headings, covering these problems Conclusion. Bacteremia and sepsis caused by S.aureus is not uncommon and severe infection which occurs everywhere, but remains to be poorly understood. The single isolation of S.aureus from the blood always is to be considered as clinically significant due to the high pathogenicity, high probability of infection and complications, rarity of contamination of blood samples with S.aureus. In cases of the isolation of staphylococci from the blood there is required an immediate and thorough search for any focus of invasion and deep metastatic foci of infection. There are strong evidences that the removal of the origin or the drainage of the locus of infection improves the results of the treatment. There is substantially less certainty about the patients with uncomplicated infections that can receive short courses of ABT. There is discussed the optimal choice of antibiotics, the duration and method of administration for the treatment of S. aureus bacteremia (SAB). Available data indicate to the more higher efficiency of f-lactams compared with glycopeptides for the treatment for infections caused by methicillin-sensitive SAB, the emergence of glycopeptide-intermediate Staphylococcus aureus (GISA) or hetero-GISA reduces the role of glycopeptides in the treatment of bacteremia caused by MRSA. Daptomycin showed the high efficacy in the treatment for severe staphylococcal infections accompanied by bacteremia and sepsis, especially when using in a dose of 6 mg/kg/ day and above. There is insufficient data for the assertion that cephalosporins are also effective as penicillins for treating SAB, but they are probably more effective than vancomycin for the treatment of methicillinsensitive SAB. The optimal duration of treatment is considered to be 10-14 days of intravenous administration for most cases of uncomplicated SAB associated with vascular catheterization, upon condition of the removal of the catheter and low risk of endocarditis.

Epidemiology of Staphylococcus aureus Bacteraemia at a Tertiary Children’s Hospital in Cape Town, South Africa

Background Staphylococcus aureus is an important pathogen in paediatric patients with bloodstream infections. The epidemiology of S. aureus bacteraemia, however, has not been well documented in children in South Africa.MethodsA retrospective study was conducted at a children’s hospital in Cape Town, South Africa, to investigate the epidemiology of S. aureus bacteraemia from 2007-2011. The incidence, clinical presentation, risk factors, management and outcomes of methicillin sensitive S. aureus (MSSA) and methicillin resistant S. aureus (MRSA) bacteraemia were compared.ResultsOver the five year study period, 365 episodes of S. aureus bacteraemia were identified. The annual incidence was 3.28 cases per 1000 hospital admissions. MRSA was responsible for 26% of S. aureus bacteraemia and 72% of nosocomial infections. Only six possible cases of community-acquired MRSA infections were described. MSSA bacteraemia was more likely to present as pulmonary and bone or joint infections, while bacteraemia without a source was the most common presentation with MRSA. Infants, children with malnutrition, and residents of long-term care facilities were at highest risk for MRSA bacteraemia. The overall case fatality rate for S. aureus bacteraemia was 8.8% over five years, with MRSA being the only significant risk factor for mortality.ConclusionThe incidence of S. aureus bacteraemia and MRSA bacteraemia in children has remained stable over the past five years. MRSA is a predominantly nosocomial pathogen in children with S. aureus bacteraemia in Cape Town, South Africa.

Staphylococcus Aureus colonization and bacteremia in children with cancer.

Abstract 3666Poster Board III-602 BackgroundStaphylococcus aureus is an important cause of blood stream infections in children and adults. In recent years, new strains of methicillin-resistant S. aureus (MRSA), also known as community-acquired (CA)-MRSA have been isolated from otherwise healthy individuals. These strains frequently carry the Panton-Valentine Leukocidin (PVL) leukotoxin and belong to spa type 8; USA300 genotype, which is the most common strain causing CA-MRSA infections in the U.S. The clinical course of infections with PVL-positive S.aureus strains appears to be more severe than infection from PVL-negative strains. Bacteremia due to these strains has been reported in children, adolescents and adults. It is not known if methcillin-resistance or infection with CA-MRSA strains adversely affects outcome in children with cancer. Colonization of MRSA in healthy children has increased significantly since 2001 and has shown to be a risk factor for subsequent infection. However the prevalence of nasal and rectal colonization with MRSA; in particular with PVL-positive strains and the relationship between colonization and infection is not known in children or adults with cancer. MethodsThe epidemiology of MRSA and methicillin-sensitive S.aureus (MSSA) bacteremia and prevalence of MRSA nasal and rectal colonization in children with cancer was retrospectively studied from 2000 to 2007. Medical record review included patient demographics, underlying disease and antimicrobial susceptibility patterns of the MRSA and MSSA bacteremia isolates. Molecular typing was performed by polymerase chain reaction (PCR) on all isolates for detection of the PVL genes. Staphylococcus cassette chromosome (SCC) mec and spa typing was performed on all PVL-positive MRSA and MSSA bacteremia isolates and MRSA isolates causing colonization and infection. Demographic and treatment variables were compared between patients with MRSA and MSSA bacteremia and patients with PVL-positive and PVL-negative MRSA and MSSA bacteremia using exact two-sample Wilcoxon rank sum test or robust rank sum test for unequal variances and Fisher's exact chi-square test. The trend of MRSA/MSSA bacteremia and MRSA colonization was evaluated by logistic regression models. ResultsTen (19%) MRSA and 42 (81%) MSSA isolates from clinically distinct infectious bacteremic episodes were collected from 52 patients with cancer during the eight year study period. The proportion of cancer patients with MRSA, or MSSA bacteremia did not change significantly over the duration of the study. A third of the patients, 17 (33%), had complications. Thirty-eight (73%) of the bacteremic episodes were catheter-related. Catheters were removed significantly more often for MRSA infections than for MSSA infections for persistently positive blood cultures or complications (p=0.003). Subcutaneous ports was removed significantly more often than Hickman catheters (p= 0.005). The number of patients with persistently positive MRSA bacteremia were higher as compared to MSSA bacteremia (p= 0.004). Methicillin resistance was associated with decreased susceptibility to erythromycin (p=0.0003) and gentamicin (p=0.03). The difference in PVL positivity between MRSA and MSSA was statistically significant (P=0.01). None of the other variables studied including complications were significantly different between patients with MRSA or MSSA bacteremia or between patients with PVL-positive and PVL-negative S.aureus bacteremia. The number of patients colonized with MRSA compared to the total number of samples tested increased significantly between 2000-2001 and 2006-2007 (p=0.0007). PVL-positivity was associated both with increased colonization (p=0.004) and with an increased risk of infection (p=0.0005). There was a discordance in the spa types between the colonization and infection isolates. ConclusionsThis report represents the first description of the epidemiology of S.aureus bacteremia and colonization including analysis of PVL-positive strains in children with cancer. Methicillin-resistance or PVL-positivity did not appear to be associated with a worse outcome in our patient population. The number of patients colonized with MRSA increased significantly during this time period. PVL-positivity was associated with an increased risk of colonization and infection. Further studies are needed to confirm these observations in patients with cancer. Disclosures:No relevant conflicts of interest to declare.

MRSA, screening and implications for the anaesthetist

MRSA, screening and implications for the anaesthetist

Persistent methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia due to a linezolid “tolerant” strain

Antibiotic "tolerance" is a rare cause of antibiotic failure. Antibiotic "tolerance" is defined as an minimal bactericidal concentration (MBC) 32x the minimal inhibitory concentration (MIC) of the isolate. Although susceptibility testing based on the MIC suggests susceptibility of "tolerant" strains, bactericidal concentrations are often beyond achievable serum levels and therapeutic failure may result. We present a case of persistent methicillin-sensitive S. aureus (MSSA) bacteremia due to a linezolid "tolerant" strain unresponsive to daptomycin therapy. We believe this is the first report of persistent MSSA bacteremia due to a linezolid "tolerant" strain.

New agents for Staphylococcus aureus endocarditis

The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) as well as newly discovered S. aureus strains with reduced susceptibility to vancomycin mandates development of new antistaphylococcal agents. This review summarizes currently available and forthcoming antimicrobials for treatment of S. aureus endocarditis. No new antimicrobial has been proven superior to antistaphylococcal penicillins for treatment of methicillin-sensitive S. aureus (MSSA) endocarditis. Vancomycin has become standard treatment for MRSA but poor outcomes have been reported, both with susceptible and intermediately resistant S. aureus strains (VISA). Linezolid has successfully treated individual cases of MRSA endocarditis, but limitations include long-term safety. Daptomycin has recently been proven effective and well tolerated for MSSA and MRSA bacteremia, including right-sided endocarditis. New glycopeptides, including dalbavancin and telavancin, as well as the new cephalosporin ceftobiprole, have not yet been studied for treatment of endocarditis but appear active against MRSA and potentially VISA. Antistaphylococcal penicillins remain the treatment of choice for MSSA. Of the currently available newer agents, daptomycin appears to have the most rapid bactericidal activity and provides a much-needed alternative to vancomycin for treatment of MRSA or MSSA bacteremia and right-sided endocarditis.

Comparison of community-acquired methicillin-resistant Staphylococcus aureus bacteremia to other staphylococcal species in a neonatal intensive care unit

Hospital acquired infections including staphylococcal species are common in neonatal intensive care units. Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) was recently observed in our unit. The clinical and laboratory characteristics of all neonates with Staphylococcus aureus bacteremia during an 11-year period were retrospectively reviewed. Three groups of patients were compared: 1. Patients with CA-MRSA defined as MRSA-resistant only to beta-lactams, but sensitive to all other antibiotic groups and carried SCCmec IV. 2. Patients with multi-drug-resistant (MDR)-MRSA and 3. Patients with MSSA (methicillin-sensitive S. aureus). Forty-three neonates with documented S. aureus bacteremia were included. Of these 41 were preterm babies. Eleven infants had CA-MRSA, 20 had MDR-MRSA and 12 had MSSA bacteremia, the Panton-Valentine-Leukocidine gene (pvl-gene) was not present in any of these strains. Risk factors, clinical manifestations and laboratory tests were similar in all three groups studied. Although neonates infected with CA-MRSA were more premature and had more related diseases, the mortality rate was similar in all groups (9.1% in the CA-MRSA group). Skin infections, osteomyelitis or pneumatocele were not observed more frequently in the CA-MRSA group. We did not find significant differences in risk factors or outcomes in neonates in the three groups. One possible explanation for this observation is that the CA-MRSA outbreak strain did not contain the pvl-gene, which has been suggested to be a significant virulence factor.

Staphylococcus aureus bacteremia and endocarditis: the Grady Memorial Hospital experience with methicillin-sensitive S aureus and methicillin-resistant S aureus bacteremia

Background Staphylococcus aureus has become the leading cause of endocarditis in most published series, and nosocomial acquisition is becoming more frequent. Previous studies involved community acquired methicillin-sensitive S aureus (MSSA), but recently, methicillin-resistant S aureus(MRSA) infection has increased. This may reflect the growing presence of this microorganism in clinical practice. Few data exist comparing the relative rates of endocarditis with MSSA and MRSA bacteremia. The purpose of this study was to compare these rates in a bacteremic population referred for diagnostic echocardiography. Methods Since July 1999, the demographic and clinical information of 104 consecutive patients with at least 2 blood cultures with positive results for S aureus who were referred for echocardiography to be evaluated for endocarditis at Grady Memorial Hospital (Atlanta, Ga) have been entered into a database. This database has further been restricted to patients who have undergone either a transesophageal echocardiogram or a transthoracic echocardiogram. Results Of the 104 patients with S aureus bacteremia, 53 had an infection of MSSA and 51 had an infection of MRSA. There were 33 patients (31.7%) with echocardiographically confirmed endocarditis, 23 patients (43.4%) in the MSSA group versus10 patients (19.6%) in the MRSA group ( P <.009). Community-acquired MSSA bacteremia was the cause of most of the community-acquired S aureus endocarditis (20 patients [87%] vs 3 patients [30%], P = .004), and the nosocomial-acquired MRSA bacteremia was the cause of most of the nosocomial-acquired S aureus endocarditis (3 patients [13%] vs 7 patients [70%], P = .0001). Conclusion Our study confirms that S aureus bacteremia is associated with high rates of endocarditis. MSSA bacteremia is associated with higher rates of endocarditis than MRSA. Community MSSA is the cause of most of the community endocarditis, whereas nosocomial MRSA is the cause of most of the MRSA endocarditis. Patients with S aureus bacteremia should be aggressively evaluated for endocarditis.

Vancomycin for Staphylococcus aureus therapy of respiratory tract infections: the end of an era?

In 1991, Karchmer [1] raised several key issues related to the pathogenesis and optimal treatment of Staphylococcus aureus infections. The main issue concerned the role of vancomycin in treating serious or invasive methicillin-sensitive S. aureus ( MSSA) and methicillinresistant S. aureus (MRSA) infections. He recognized and envisaged the current global epidemic of MRSA infections in hospitals [2], and to a lesser extent the community [3], and concluded that ‘there is an urgent need for effective alternatives to vancomycin for the treatment of MRSA infections’. Since then we have emerging evidence, a recent meta-analysis, that in patients with S. aureus -related bacteraemia, MRSA is an independent risk factor for higher mortality compared with MSSA bacteraemia [4]. This adds further support to the ongoing debate about the virulence of MRSA infections compared with MSSA and the need for optimal antibiotics at the onset of treatment. The reality, a decade later, is the occurrence of a broad range of serious and invasive MRSA infections, often in vulnerable patients in ‘high risk’ clinical settings [5]. The need to treat many of these patients empirically with a view to ‘covering’ the most likely offending pathogens is perceived to be high if the critical therapeutic window of opportunity for optimal antibiotic therapy is not to be missed. The undesirable consequences of not getting the ‘right drug, to the right patient, in the right dose at the right time’ are clear [6]. The rapid laboratory and clinical capability of predicting patients likely to be infected with MRSA continues to improve but is by no means ideal [7,8]. Additionally, we are witnessing the concurrent rise in S. aureus strains that exhibits glycopeptide-intermediate susceptibility from several countries including Japan, France and US that has been subject to recent review [9]. For example, strains with MIC to vancomycin of 4 mg/l have caused clinical infections that failed to respond to vancomycin therapy. Traditionally, when the effectiveness of an antimicrobial agent in serious infections is considered, there has been an overemphasis on the need for bactericidal activity as a pre-requisite for a good outcome. Many of us now accept that local tissue penetration should be considered of equal importance. This is particularly important when looking at treatment options for staphylococcal infections, especially in tissues such as lung or the endovascular lining. Vancomycin is still regarded as the ‘gold-standard’ therapy for serious or invasive MRSA infections. Considering Karchmer’s concerns of a decade ago, we examine what more have we learnt about vancomycin treatment and summarize the emerging evidence for new or combination therapies. Vancomycin is bactericidal and appears to exert its effect by binding to the precursor units of peptidoglycan synthesis inhibiting the transpeptidase reaction. It exhibits concentration-independent bactericidal action against susceptible bacteria and is more bactericidal in aerobic conditions. This effect is exerted without a lag period but acts only on multiplying organisms and with a post-antibiotic effect of about 2 h. Against MSSA, it is a less active agent than b-lactams [1,10 /12] by virtue of being more slowly and incompletely bactericidal compared with equivalent concentrations of a b-lactam. A recent illustration of this phenomenon in clinical practice was demonstrated by Tam et al. [13] in haemodialysis patients with MSSA bacteraemia. This study revealed that persistent bacteraemia 24 h after therapy was significantly greater (37% vs. 25%, P /0.05) in patients initially treated with vancomycin compared with those with a b-lactam. Additionally, in patients with MSSA endocarditis and related bacteraemia, there * Corresponding author. Tel.: /44-1382-660-111; fax: /44-1382816-178. E-mail address: dilip.nathwani@tuht.scot.nhs.uk (D. Nathwani). International Journal of Antimicrobial Agents 21 (2003) 521 /524

Risk of death from methicillin‐resistant Staphylococcus aureus bacteraemia: a meta‐analysis

To estimate the risk of death from healthcare-associated (nosocomial) bacteraemia caused by methicillin-resistant Staphylococcus aureus (MRSA), and compare it with that of nosocomial bacteraemia caused by methicillin-sensitive S. aureus (MSSA), by meta-analysis of selected studies. Medline, EMBASE, Current Contents and Cochrane Library were searched for the period January 1978 (or earliest date of the database, if later than 1978) to December 2000. Studies which compared mortality of nosocomial MRSA and MSSA bacteraemia. Nine studies were analysed. All but one found an increased relative risk (RR) of death from MRSA bacteraemia, with RR ranging from 0.89 to 4.94. Meta-analysis showed that patients with MRSA bacteraemia have an RR of death, compared with patients with MSSA bacteraemia, of 2.12 (95% CI, 1.76-2.57) using the fixed-effect method, and 2.03 (95% CI, 1.55-2.65) using the random-effect method. MRSA bacteraemia is associated with a real increase in risk of death, further justifying ongoing MRSA surveillance and control in healthcare facilities.

Risk of death from methicillin-resistant Staphylococcus aureus bacteraemia: a meta-analysis.

To estimate the risk of death from healthcare-associated (nosocomial) bacteraemia caused by methicillin-resistant Staphylococcus aureus (MRSA), and compare it with that of nosocomial bacteraemia caused by methicillin-sensitive S. aureus (MSSA), by meta-analysis of selected studies. Medline, EMBASE, Current Contents and Cochrane Library were searched for the period January 1978 (or earliest date of the database, if later than 1978) to December 2000. Studies which compared mortality of nosocomial MRSA and MSSA bacteraemia. Nine studies were analysed. All but one found an increased relative risk (RR) of death from MRSA bacteraemia, with RR ranging from 0.89 to 4.94. Meta-analysis showed that patients with MRSA bacteraemia have an RR of death, compared with patients with MSSA bacteraemia, of 2.12 (95% CI, 1.76-2.57) using the fixed-effect method, and 2.03 (95% CI, 1.55-2.65) using the random-effect method. MRSA bacteraemia is associated with a real increase in risk of death, further justifying ongoing MRSA surveillance and control in healthcare facilities.