Tolerability of prolonged linezolid therapy in bone and joint infection: protective effect of rifampicin on the occurrence of anaemia?

J Antimicrob Chemother. 2010 Jul 29;

Authors: Legout L, Valette M, Dezeque H, Nguyen S, Lemaire X, Loïez C, Caillaux M, Beltrand E, Dubreuil L, Yazdanpanah Y, Migaud H, Senneville E

Background Linezolid therapy has shown high rates of clinical success in patients with osteomyelitis and prosthetic joint infections caused by Gram-positive cocci. Recent studies have demonstrated that linezolid/rifampicin combination therapy prevents the emergence of rifampicin-resistant mutations in vitro. However, linezolid/rifampicin combination-related haematological and neurological toxicities have not been evaluated. Objectives To assess the tolerability of prolonged linezolid/rifampicin combination therapy compared with other linezolid-containing regimens in patients with bone and joint infections. Methods We reviewed the medical records of 94 patients who had received linezolid for >4 weeks after bone and joint infections. Anaemia was defined as a >/=2 g/dL reduction in haemoglobin, leucopenia as a total leucocyte count <4 x 10(9)/L, and thrombocytopenia as a reduction in platelet count to <75% of baseline. Results Anaemia was less frequent among patients on linezolid/rifampicin combination therapy than among patients on linezolid alone or in combination with other drugs (9.3%, 44% and 52%, respectively; P < 0.01). In multivariate analysis, age and treatment group were independently associated with anaemia. Thrombocytopenia was reported in 44% of patients on linezolid/rifampicin combination therapy, in 48% of patients on linezolid alone and in 57.7% of patients on other linezolid-containing regimens. Age was the only variable associated with thrombocytopenia (P = 0.019) in univariate analysis. Conclusions Linezolid/rifampicin combination therapy was associated with a significantly reduced incidence of anaemia among patients with bone and joint infections, but it did not have an effect on thrombocytopenia and peripheral neuropathy rates. Linezolid/rifampicin combination therapy was not associated with poor clinical outcomes.

PMID: 20675299 [PubMed - as supplied by publisher]

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Newer antibacterial agents and their potential role in cystic fibrosis pulmonary exacerbation management.

J Antimicrob Chemother. 2010 Jul 6;

Authors: Parkins MD, Elborn JS

Pulmonary exacerbations in cystic fibrosis (CF) are frequent events and account for a substantial proportion of the burden of morbidity and mortality in this disease. Antibacterial therapies to treat pulmonary exacerbations are instituted empirically and are individualized based on both patient factors (severity of exacerbation, frequency of exacerbation, recent courses of anti-infectives) and pathogen factors (previously isolated pathogens and in vitro predicted susceptibilities). However, the epidemiology of pathogens infecting CF airways is changing, with increased incidence of methicillin-resistant Staphylococcus aureus (MRSA), drug-resistant Pseudomonas aeruginosa and other Gram-negative non-fermenters such as Stenotrophomonas maltophilia and Achromobacter xylosoxidans. Accordingly, a great need for new and novel agents for the management of acute exacerbations in CF exists. While several antibiotics have recently been approved or are close to approval for clinical use, frequently their emphasis has been for Gram-positive, and specifically MRSA-related, disease. Despite this, these agents may have a role in CF-related exacerbations. This article reviews the spectrum of activity, pharmacokinetics and clinical and theoretical evidence for the use of newer agents including tigecycline, doripenem and ceftobiprole in the management of CF pulmonary exacerbations. Appropriate use of these agents in CF will require detailed CF-specific pharmacokinetic and pharmacodynamic data.

PMID: 20605846 [PubMed - as supplied by publisher]

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A multicentre study to evaluate the impact of timing of caspofungin administration on outcomes of invasive candidiasis in non-immunocompromised adult patients.

J Antimicrob Chemother. 2010 Jun 16;

Authors: Hsu DI, Nguyen M, Nguyen L, Law A, Wong-Beringer A

Objectives Candida non-albicans species cause an increasing proportion of invasive candidiasis (IC). Prompt initiation of effective antifungal therapy has been shown to positively impact the outcomes of IC. Caspofungin is often reserved as a second-line agent after suboptimal response to initial therapy. We determined the impact of the timing of caspofungin administration on outcomes of IC. Methods Medical records were reviewed on all hospitalized adults who received >/=72 h of caspofungin for IC (isolation of Candida species from blood, intra-abdominal or other sterile sites). Clinical data were extracted from medical charts and recorded. Patients were classified based on delayed initiation (DI; >3 days) versus early initiation (EI; </=3 days) of caspofungin relative to the time the culture was obtained. Results A total of 169 patients received caspofungin for IC; Candida glabrata (n = 78, 46%) was the most common cause, followed by mixed species (n = 36, 21%), Candida albicans (n = 36, 21%), Candida parapsilosis (n = 9, 6%), Candida tropicalis (n = 6, 3%), Candida krusei and other species (n = 4, 2%). Infection sites were bloodstream related (n = 119, 71%), intra-abdominal (n = 44, 26%) and other sterile sites (n = 6, 3%). DI of caspofungin was associated with a lower response rate (35/62, 56% versus 82/107, 77%; P = 0.006), longer time to achieve clinical stability (10 versus 4 days; P = 0.002) and longer length of stay after isolation of the organism (28 versus 21 days; P = 0.007), compared with EI (n = 107). Conclusions Non-albicans Candida species accounted for the majority of IC in caspofungin-treated patients. Improved outcomes were observed for patients initiated with caspofungin within 72 h of positive culture compared with those who received delayed therapy.

PMID: 20554567 [PubMed - as supplied by publisher]

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Efficacy of the new cephalosporin ceftaroline in the treatment of experimental methicillin-resistant Staphylococcus aureus acute osteomyelitis.

J Antimicrob Chemother. 2010 Jun 8;

Authors: Jacqueline C, Amador G, Caillon J, Le Mabecque V, Batard E, Miègeville AF, Biek D, Ge Y, Potel G, Hamel A

Objectives To evaluate the activity of a new cephalosporin, ceftaroline, in comparison with other antistaphylococcal drugs (linezolid and vancomycin) at projected human therapeutic doses against methicillin-resistant Staphylococcus aureus (MRSA) and glycopeptide-intermediate S. aureus (GISA) strains. Methods Using a rabbit experimental model of acute osteomyelitis, efficacy was assessed following 4 days of treatment by colony counts of infected bone tissues (joint fluid, femoral bone marrow and bone). Results Although vancomycin remains the standard treatment for MRSA osteomyelitis, it was ineffective against the MRSA strain and poorly active against GISA infections in this model. Ceftaroline and linezolid demonstrated significant activity in bone marrow and bone, and were significantly better than vancomycin treatment. However, ceftaroline was the only drug to exhibit significant activity against MRSA in infected joint fluid. Conclusions The present study supports ceftaroline as a promising therapeutic option for the treatment of severe MRSA infections, including osteomyelitis.

PMID: 20530506 [PubMed - as supplied by publisher]

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Efficacy of the new cephalosporin ceftaroline in the treatment of experimental methicillin-resistant Staphylococcus aureus acute osteomyelitis.

J Antimicrob Chemother. 2010 Jun 8;

Authors: Jacqueline C, Amador G, Caillon J, Le Mabecque V, Batard E, Miègeville AF, Biek D, Ge Y, Potel G, Hamel A

Objectives To evaluate the activity of a new cephalosporin, ceftaroline, in comparison with other antistaphylococcal drugs (linezolid and vancomycin) at projected human therapeutic doses against methicillin-resistant Staphylococcus aureus (MRSA) and glycopeptide-intermediate S. aureus (GISA) strains. Methods Using a rabbit experimental model of acute osteomyelitis, efficacy was assessed following 4 days of treatment by colony counts of infected bone tissues (joint fluid, femoral bone marrow and bone). Results Although vancomycin remains the standard treatment for MRSA osteomyelitis, it was ineffective against the MRSA strain and poorly active against GISA infections in this model. Ceftaroline and linezolid demonstrated significant activity in bone marrow and bone, and were significantly better than vancomycin treatment. However, ceftaroline was the only drug to exhibit significant activity against MRSA in infected joint fluid. Conclusions The present study supports ceftaroline as a promising therapeutic option for the treatment of severe MRSA infections, including osteomyelitis.

PMID: 20530506 [PubMed - as supplied by publisher]

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Related Articles

Proposed changes to management of lower respiratory tract infections in response to the Clostridium difficile epidemic.

J Antimicrob Chemother. 2010 Apr;65(4):608-18

Authors: Chalmers JD, Al-Khairalla M, Short PM, Fardon TC, Winter JH

Clostridium difficile infection (CDI) remains a major healthcare problem associated with antibiotic use in hospitals. Recent years have seen a dramatic increase in the incidence of CDI in the UK and internationally. Lower respiratory tract infections (LRTIs) are the leading indication for antibiotic prescription in hospitals and are therefore a critical battleground in the fight against inappropriate antibiotic use and healthcare-associated infections. This article reviews the evidence for interventions to reduce CDI in hospitalized patients with LRTIs. Reducing prescriptions of cephalosporins and fluoroquinolones in favour of penicillin-based regimens and increased use of tetracyclines have been proposed. Expanding outpatient management of LRTIs and reducing length of hospital stay will limit patient exposure to the healthcare environment in which C. difficile is most easily acquired. Intravenous (iv) broad-spectrum antibiotics are often prescribed when narrower spectrum, oral antimicrobials would be equally effective and, in a proportion of patients, antibiotic therapy is used unnecessarily. Shorter antibiotic regimes may be as effective as prolonged therapy and reduce antibiotic-related complications. Early switch from iv to oral therapy allows simpler antibiotic regimens and facilitates early discharge from hospital. Simple improvements in the management of LRTIs have the potential to reduce the incidence of healthcare-associated infections.

PMID: 20179023 [PubMed - indexed for MEDLINE]

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Risk factors for mortality in patients with persistent methicillin-resistant Staphylococcus aureus bacteraemia in a tertiary care hospital in Taiwan.

J Antimicrob Chemother. 2010 May 28;

Authors: Lin SH, Liao WH, Lai CC, Liao CH, Tan CK, Wang CY, Huang YT, Hsueh PR

Objectives To investigate the determinants of outcome in patients with persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia. Methods All patients >/=18 years old with MRSA bacteraemia for >/=7 days from 2000 to 2008 treated at National Taiwan University Hospital were investigated. The associations of mortality with clinical characteristics, management and vancomycin MICs for serial MRSA isolates were analysed. Results Persistent MRSA bacteraemia occurred in 227 patients. Decreasing trends in the incidence of MRSA bacteraemia (P < 0.001) and persistent MRSA bacteraemia (P = 0.031) were found. Elevated vancomycin MICs for subsequent MRSA isolates were found in 49 (24.6%) of 199 patients, especially those with infective endocarditis (41.9% versus 21.4%; P = 0.027). Metastatic infection [odds ratio (OR) 5.23; 95% confidence interval (CI) 2.17-12.59; P < 0.001], congestive heart failure (OR 4.78; 95% CI 2.19-10.42; P < 0.001) and elevated vancomycin MICs for subsequent MRSA isolates (OR 3.21; 95% CI 1.46-7.07; P = 0.004) were independent predictors of MRSA-related mortality, while metastatic infection (OR 3.01; 95% CI 1.45-6.28, P = 0.003) and congestive heart failure (OR 2.85; 95% CI 1.44-5.56, P = 0.003) were predictors of 30 day mortality. No significant impact of empirical glycopeptide therapy on MRSA-related (P = 0.89) or 30 day mortality (P = 0.26) was found. The 30 day mortality rate was lower in patients who received complete foci eradication (35.6% versus 51.1%; P = 0.03). Conclusions Congestive heart failure and metastatic infections were predictors of mortality. Isolates with decreased susceptibility to vancomycin that emerged during persistent MRSA bacteraemia were associated with mortality. Aggressive attempts to completely eradicate foci should be encouraged.

PMID: 20511366 [PubMed - as supplied by publisher]

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The interaction between prior antimicrobial drug exposure and resistance in human Salmonella infections.

J Antimicrob Chemother. 2010 May 27;

Authors: Koningstein M, Simonsen J, Helms M, Mølbak K

Objectives The use of antimicrobial drugs for food animals selects for resistant non-typhoid Salmonella strains, but human consumption of antimicrobial drugs may also increase the risk of subsequent infection. The aim of this study was to determine the risk of salmonellosis attributable to human consumption of antimicrobial drugs in a case-control study of 22 602 laboratory-confirmed Salmonella infections, diagnosed in Denmark between 1997 and 2005. Methods A population registry-based case-control study, using several Danish databases: the National Prescription Database; the National Registry for Enteric Pathogens; the Civil Registry System; and the Integrated Database on Labour Market Research. Results Exposure to trimethoprim, sulphonamides, broad-spectrum penicillins, tetracyclines and fluoroquinolones, during the year prior to diagnosis, was associated with an increased risk of non-typhoid Salmonella infection. Overall, the highest risk was associated with the prior use of fluoroquinolones. This risk increased as the time window of exposure approached the infection date. Previous use of fluoroquinolones was associated with an odds ratio (OR) of 4.55 [95% confidence interval (CI): 3.78-5.47] for Salmonella serotypes other than Salmonella Typhimurium or Salmonella Enteritidis, an OR of 2.21 (95% CI: 1.70-2.86) for Salmonella Typhimurium and an OR of 2.07 (95% CI: 1.76-2.42) for Salmonella Enteritidis. In particular for fluoroquinolones, there was an interaction between the pathogen resistance pattern and a history of antibiotic drug use. Conclusions The increasing use of antibiotics, particularly fluoroquinolones, is likely to result in increased incidence of foodborne infections with drug-resistant Salmonella.

PMID: 20507862 [PubMed - as supplied by publisher]

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Co-trimoxazole versus vancomycin for the treatment of methicillin-resistant Staphylococcus aureus bacteraemia: a retrospective cohort study.

J Antimicrob Chemother. 2010 May 27;

Authors: Goldberg E, Paul M, Talker O, Samra Z, Raskin M, Hazzan R, Leibovici L, Bishara J

Objectives To evaluate the efficacy and safety of co-trimoxazole versus that of vancomycin in adults with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia. Patients and methods Retrospective matched cohort study. Thirty-eight patients with MRSA bacteraemia, treated with co-trimoxazole as the main therapeutic agent, were matched with 76 patients treated with vancomycin as the main agent. The groups were matched for age, sex, functional status, endovascular source of infection, appropriateness of empirical antibiotic therapy, presence of a foreign body, sepsis severity and Charlson score. The outcomes collected were 30 day mortality, persistent bacteraemia [defined as positive blood culture (BC) >14 days after the first positive BC, but within 30 days], relapse (defined as recurrence of the same phenotype >30 days after the first positive BC within 12 months) and adverse events. Results The groups were well matched. Thirty day mortality was not significantly different between the groups [co-trimoxazole 13/38 (34.2%); vancomycin 31/76 (40.8%); odds ratio 0.76, 95% confidence interval 0.34-1.7]. There was only one case of relapse in the co-trimoxazole group (2.6%) compared with nine cases in the vancomycin group (11.8%). Incidence of relapse or persistent bacteraemia was lower in the co-trimoxazole group (3/38, 7.9%) than in the vancomycin group (13/76, 17.1%), although the difference was not statistically significant (P = 0.182). Development of renal failure was similar [co-trimoxazole 11/38 (28.9%); vancomycin 21/76 (27.6%)]. Conclusions Within the limitations of a small retrospective study, co-trimoxazole had a safety and efficacy profile similar to that of vancomycin and may offer an attractive additional therapeutic option for MRSA bacteraemia. A prospective, randomized controlled trial is warranted.

PMID: 20507860 [PubMed - as supplied by publisher]

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Effectiveness and safety of neuraminidase inhibitors in reducing influenza complications: a meta-analysis of randomized controlled trials.

J Antimicrob Chemother. 2010 May 20;

Authors: Falagas ME, Koletsi PK, Vouloumanou EK, Rafailidis PI, Kapaskelis AM, Rello J

Background Several studies suggest that neuraminidase inhibitors (NIs) can reduce the duration of influenza symptoms. However, data regarding their effectiveness in reducing influenza complications are scarce. Methods We evaluated the effectiveness of NIs in reducing influenza complications and mortality of patients with seasonal influenza, by performing a meta-analysis of randomized controlled trials (RCTs), retrieved from PubMed, Cochrane Central Register of Controlled Trials and Scopus databases, comparing NIs with placebo. Results Eleven RCTs (10 double-blind) were included; 8 involved adults/adolescents. In total, 5315 patients were included; 3491 (65.7%) with confirmed infection. Total influenza-related complications were significantly less likely in otherwise healthy patients with confirmed influenza infection that were treated with NIs versus placebo [7 RCTs, 2621 patients, risk ratio (RR) = 0.74, 95% confidence interval (CI) = 0.58-0.95] This finding was more pronounced in high-risk patients [4 RCTs, 475 patients, RR = 0.37, 95% CI = 0.24-0.59]; P < 0.01 for the chi(2) test for subgroup differences. In the comparisons regarding individual complications, a trend in favour of NIs was observed. Acute otitis media was significantly less likely in patients with confirmed influenza infection treated with NIs versus placebo (3 RCTs, 1124 patients, RR = 0.50, 95% CI = 0.30-0.85). No differences were found in the comparisons regarding the safety outcomes. No deaths were observed in trials that reported on mortality. Conclusions NIs seem to be effective in reducing total influenza-related complications in otherwise healthy and high-risk patients, and have an acceptable safety profile. However, RCTs providing separate data for mild to serious complications and detailed reporting of adverse events and mortality are needed.

PMID: 20488984 [PubMed - as supplied by publisher]

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Ertapenem administered as outpatient parenteral antibiotic therapy for urinary tract infections caused by extended-spectrum-{beta}-lactamase-producing Gram-negative organisms.

J Antimicrob Chemother. 2010 May 11;

Authors: Bazaz R, Chapman AL, Winstanley TG

Objectives Infections with extended-spectrum-beta-lactamase-producing organisms are an increasing public health concern. We reviewed the use of an outpatient parenteral antibiotic therapy (OPAT) programme to facilitate the early discharge from hospital of patients with ESBL-associated urinary tract infections. Methods A retrospective review of patients treated for urinary tract infections caused by ESBL-producing organisms through the OPAT programme at the Royal Hallamshire Hospital, Sheffield, UK over a 4 year period to January 2010 was conducted. Data on patient demographics, clinical presentation and laboratory results were collected. Results Twenty-four OPAT episodes involving 11 patients were identified. Six patients (54.5%) had an underlying urological abnormality on presentation to OPAT. All patients were treated with parenteral ertapenem. Two patients had multiple infections treated by OPAT. The mean duration of the OPAT episodes was 9.9 days (range 3-42). A total of 238 inpatient bed days were avoided, with resultant cost savings. Conclusions Ertapenem administration through OPAT may help to decrease the costs associated with ESBL infections by reducing the number of inpatient bed days required for their successful treatment.

PMID: 20460397 [PubMed - as supplied by publisher]

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Soft tissue and bone penetration abilities of daptomycin in diabetic patients with bacterial foot infections.

J Antimicrob Chemother. 2010 Apr 7;

Authors: Traunmüller F, Schintler MV, Metzler J, Spendel S, Mauric O, Popovic M, Konz KH, Scharnagl E, Joukhadar C

Objectives In the attempt to overcome increasing glycopeptide- and methicillin-resistant soft tissue infections, daptomycin is presently considered as an attractive alternative to the class of glycopeptides. However, daptomycin dosing and its ability to penetrate into inflamed target tissues are still a matter of controversy. Thus, in the present investigation, we set out to evaluate daptomycin’s ability to penetrate into inflamed subcutaneous adipose tissue and bone in diabetic patients presenting with severe bacterial foot infection. Patients and methods The microdialysis technique was utilized to collect interstitial space fluid from inflamed subcutaneous adipose tissue and metatarsal bone. Plasma and unaffected subcutaneous adipose tissue served as reference compartments. Serial sampling of specimens at steady-state was performed from 0 to 8 h post-dose in five patients (Group A) and from 8 to 16 h after study drug administration in another group of four patients (Group B). In all subjects, daptomycin was administered intravenously once daily at a dosage of 6 mg/kg body weight for 4 consecutive days at minimum. Results Equilibrium between free tissue and plasma concentrations was achieved approximately 2 h post-infusion. Under steady-state conditions, the degree of tissue penetration was assessed by the calculation of the ratio of free (f) AUC of daptomycin in plasma to the fAUC in tissues. The mean ratios of the fAUC(0-16 tissue) to the fAUC(0-16 plasma) were 1.44, 0.98 and 1.08 for healthy tissue, inflamed subcutaneous adipose tissue and bone, respectively. The corresponding ratios of the fAUCs from 0 to 24 h were 1.54, 1.06 and 1.17, respectively. Conclusions With the reservation that pharmacokinetic-pharmacodynamic targets for daptomycin in tissues are currently not established, we conclude that daptomycin given at intravenous doses of 6 mg/kg body weight once daily may be considered an effective treatment regimen in diabetic patients suffering from bacterial foot infection and osteomyelitis.

PMID: 20375031 [PubMed - as supplied by publisher]

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Improved susceptibility of Gram-negative bacteria in an intensive care unit following implementation of a computerized antibiotic decision support system.

J Antimicrob Chemother. 2010 Mar 9;

Authors: Yong MK, Buising KL, Cheng AC, Thursky KA

Objectives Emergence of multiresistant Gram-negative organisms in intensive care units (ICUs) throughout the world is a concerning problem. Therefore we undertook a study to follow the resistance patterns of the most common clinically isolated Gram-negative organisms within our ICU following an antibiotic stewardship intervention to evaluate whether a reduction in broad-spectrum antibiotics improves local antibiotic resistance patterns. Methods This prospective study was conducted over a 7 year period within an ICU at a tertiary teaching hospital in Melbourne, Australia. All clinically isolated Gram-negative organisms were identified and extracted from the hospital pathology system. Three monthly antibiograms were created. The pre-interventional period occurred between January 2000 and June 2002 (10 quarters) and the post-interventional period was defined from July 2002 to December 2006 (18 quarters). Segmented linear regression was used to analyse for a difference in the rates of change in susceptibility. Results A total of 2838 Gram-negative organisms were isolated from clinical sites from ICU patients during the study period. There was significant improvement in susceptibility of Pseudomonas to imipenem 18.3%/year [95% confidence interval (CI): 4.9-31.6; P = 0.009] and gentamicin 11.6%/year (95% CI: 1.8-21.5; P = 0.02) compared with the pre-intervention trend. Significant changes in the rates of gentamicin and ciprofloxacin susceptibility were also observed in the inducible Enterobacteriaceae group although these were less clinically significant. Conclusions This study demonstrates improved antibiotic susceptibility of ICU Gram-negative isolates including Pseudomonas following an intervention aimed at reducing broad-spectrum antibiotics.

PMID: 20215130 [PubMed - as supplied by publisher]

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Candidaemia in adult cancer patients: risks for fluconazole-resistant isolates and death.

J Antimicrob Chemother. 2010 Mar 4;

Authors: Slavin MA, Sorrell TC, Marriott D, Thursky KA, Nguyen Q, Ellis DH, Morrissey CO, Chen SC,

Background Candidaemia in cancer patients is associated with increasing fluconazole resistance. Models for predicting such isolates and their clinical impact are required. Methods Clinical, treatment and outcome data from a population-based candidaemia survey (2001-2004) were collected at 5 and 30 days after diagnosis. Speciation and antifungal susceptibility testing was performed. Results There were 138 candidaemia episodes (33% Candida albicans) in adults with haematological malignancies and 150 (51% C. albicans) in adults with solid organ malignancies. Thirty-nine isolates had fluconazole MICs of >/=64 mg/L and 40 had MICs of 16-32 mg/L (predominantly Candida glabrata and Candida krusei). By multivariate analysis, triazole therapy, gastrointestinal tract (GIT) surgery in the 30 days before candidaemia and age >65 years were predictive of fluconazole-resistant candidaemia. Thirty day crude mortality was 40% in haematology patients and 45% in oncology patients. Fluconazole-resistant isolates were associated with increased risk of mortality by univariate (P = 0.04) and Kaplan-Meier survival analyses. By Cox proportional hazards modelling, the strongest predictors of mortality at onset of candidaemia were invasive ventilation, elevated creatinine, intensive care unit (ICU) admission and receipt of systemic triazoles or corticosteroids in the previous 30 days. Removal of a central venous access device (CVAD) at or within 5 days of onset was associated with decreased mortality. Conclusions Risk factors for fluconazole-resistant candidaemia in adults with cancer include fluconazole/triazole exposure and GIT surgery. ICU admission, invasive ventilation, renal impairment, age >65 years and prior exposure to corticosteroids and triazoles are risk factors for death. CVAD removal reduced mortality. These findings should be integrated into surveillance and treatment algorithms.

PMID: 20202987 [PubMed - as supplied by publisher]

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Predictors of persistent methicillin-resistant Staphylococcus aureus bacteraemia in patients treated with vancomycin.

J Antimicrob Chemother. 2010 Mar 3;

Authors: Yoon YK, Kim JY, Park DW, Sohn JW, Kim MJ

Objectives The high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) coupled with an increase in vancomycin use have induced vancomycin tolerance in MRSA, adversely affecting the outcome of MRSA bacteraemia. This study aimed to identify predictors of persistent MRSA bacteraemia (PMRSAB) in patients treated with vancomycin. Methods A retrospective, case-control study was performed at a university hospital in Korea from January 2006 to February 2009. Subjects included 96 patients who had MRSA bacteraemia and received vancomycin under therapeutic drug monitoring. We compared the clinical characteristics, management and outcomes of cases with PMRSAB (>/=7 days, n = 31) with controls with non-PMRSAB (</=3 days, n = 32). Vancomycin MICs were determined by the Vitek 2 system. Results Of 96 patients with MRSA bacteraemia, MRSA isolates from 21 patients (21.9%) showed a vancomycin MIC of 2 mg/L. Independent predictors of PMRSAB were: retention of implicated medical devices [odds ratio (OR), 10.35; 95% confidence interval (CI), 1.03-104.55]; MRSA infection of at least two sites (OR, 10.24; 95% CI, 1.72-61.01); and vancomycin MIC of 2 mg/L (OR, 6.34; 95% CI, 1.21-33.09). The frequency of side effects and mean trough serum vancomycin concentrations were not significantly different between the two groups. Sixteen patients with PMRSAB subsequently received teicoplanin +/- arbekacin, linezolid or quinupristin/dalfopristin, due to vancomycin failure or intolerance. Conclusions To minimize the risk of PMRSAB, early removal of implicated devices and evaluation for metastatic infections should be encouraged. Alternative antibiotic therapy is warranted for infections due to isolates with elevated vancomycin MICs, as well as for the high rates of side effects.

PMID: 20200036 [PubMed - as supplied by publisher]

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