Ceftaroline fosamil and treatment of acute bacterial skin and skin structure infections: CAPTURE study experience

Abstract

The Clinical Assessment Program and TEFLARO Utilization Registry (CAPTURE) is a multicentre retrospective cohort study in the USA describing treatment of acute bacterial skin and skin structure infection (ABSSSI) with ceftaroline fosamil (CPT-F). Charts for review were chosen by random selection. Among 647 evaluable patients, 52% were obese, 46% had diabetes mellitus (DM), and 19% had peripheral vascular disease (PVD). Methicillin-resistant Staphylococcus aureus (MRSA) was recovered in 28% and methicillin-susceptible S. aureus (MSSA), 11%. Antibiotics were administered prior to CPT-F treatment in 80%, and concurrently in 39%. Clinical success overall was 85%; in patients with DM, 83%; with PVD, 76%; and in obese patients, 88%. Clinical success was ≧ 79% across all infection types; 81% for MRSA and 83% for MSSA; and 86% for ceftaroline monotherapy and 84% for concurrent therapy. These high clinical success rates support CPT-F as an effective treatment option for ABSSSI, including infections due to MRSA and patients with significant co-morbidities.     

In vitro activity of ceftaroline and ceftobiprole against methicillin-resistant Staphylococcus aureus with decreased susceptibility to vancomycin isolated in paediatric patients

Minimal inhibitory concentrations (MIC, mg/l) of ceftaroline and ceftobiprole were evaluated over 70 methicillin-resistant Staphylococcus aureus (MRSA) strains with vancomycin MIC ≥1 isolated in a paediatric hospital. The proportion of non-wild-type strains (MIC?>?epidemiological cut off) was 18% for ceftobiprole and 64% for ceftaroline. Only 1.4% of strains was resistant to ceftobiprole, and none to ceftaroline. These results are worrisome, since show the presence of non-negligible proportions of MRSA strains with high MIC values for ceftaroline and ceftobiprole in a setting where both drugs were never used.     

Comparative in vitro activity of ceftaroline and comparator agents against nosocomial Gram-negative and Gram-positive clinically significant bacterial isolates from patients in a teaching hospital in Kuwait

The objective was to test the in vitro activities of ceftaroline and comparator agents against clinical isolates of Gram-negative and Gram-positive bacteria. Isolates were identified with VITEK II. Susceptibility testing was with E test. A total of 1264 isolates were tested. Compared to other cephalosporins, ceftaroline demonstrated excellent in vitro activities (MIC₉₀, ≤0.5 mg/L) against Escherichia coli, Salmonella spp. and Haemophilus influenzae. When matched with the comparator cephalosporins, ceftaroline demonstrated the greatest activity against methicillin-susceptible Staphylococcus aureus (MSSA), with MIC₉₀ of 0.25 mg/L. Ceftaroline’s MIC₉₀s against both community-associated methicillin-resistant S. aureus (MRSA) and hospital-acquired MRSA were 0.5 and 1 mg/L, respectively. Major discrepancies were noted between E test and disc diffusion tests for ceftaroline only against 16 Gram-negative and 16 Gram-positive isolates. Ceftaroline demonstrated an excellent in vitro activity against the majority of clinically significant Gram-negative and Gram-positive isolates obtained from proven cases of bacterial infections.     

Patients’ preference for radiotherapy fractionation schedule in the palliation of symptomatic unresectable lung cancer†

The palliative radiotherapeutic management of unresectable non‐small‐cell lung cancer is controversial, with various fractionation (Fx) schedules available. We aimed to determine patient’s choice of Fx schedule after involvement in a decision‐making process using a decision board. A decision board outlining the various advantages and disadvantages apparent in the Medical Research Council study of Fx schedules (17 Gy in two fractions vs 39 Gy in 13 fractions) was discussed with patients who met Medical Research Council eligibility criteria. Patients were then asked to indicate their preferred Fx schedules, reasons and their level of satisfaction with being involved in the decision‐making process. Radiation oncologists (RO) could prescribe radiotherapy schedules irrespective of patients’ preferences. Of 92 patients enrolled, 55% chose the longer schedule. English‐speaking patients were significantly more likely to choose the longer schedule (P = 0.02, 95% confidence interval: 1.2–7.6). Longer Fx was chosen because of longer survival (90%) and better local control (12%). Shorter Fx was chosen for shorter overall treatment duration (80%), cost (61%) and better symptom control (20%). In all, 56% of patients choosing the shorter schedule had their treatment altered by the treating RO, whereas only 4% of patients choosing longer Fx had their treatment altered (P < 0.001). Despite this, all (100%) patients were satisfied with being involved in the decision‐making process. The decision board was useful in aiding decision‐making, with both Fx schedules being acceptable to patients. Interestingly, despite the longer average survival associated with longer Fx, nearly half of the patients believed that this was not as important as a shorter duration of treatment and lower cost. Despite patients’ preferences, there were significant alterations of preferred schedules because of RO’s own biases.     

Activity of ceftaroline and comparator agents tested against contemporary Gram-positive and -negative (2011) isolates collected in Europe,Turkey, and Israel

Abstract

The activity of ceftaroline was tested against 8233 isolates mainly collected from bloodstream, urinary, respiratory and skin and soft tissue specimens in European medical centers during 2011. This cephalosporin displayed activity against Staphylococcus aureus (MIC₅₀, 0·25 mg/l), with greater activity against MRSA (MIC₅₀, 1 mg/l) than other β-lactams tested. Against Streptococcus pneumoniae, including penicillin-resistant strains, other streptococcal groups and Haemophilus spp., ceftaroline was highly active and MIC90 values ranged from ≤0·015 to 0·12 mg/l. Ceftaroline, like other cephalosporins, had limited activity against ESBL-phenotype Enterobacteriaceae, but showed good activity against isolates not displaying an ESBL-phenotype. Ceftaroline remains very active against MRSA and other organisms than could be associated with its approved indications in the EU (complicated skin and soft tissue infections and community-acquired pneumonia).     

Ceftaroline fosamil as first-line versus second-line treatment for acute bacterial skin and skin structure infections (ABSSSI) or community-acquired bacterial pneumonia (CABP)

The Clinical Assessment Program and Teflaro^® Utilization Registry (CAPTURE) is a multicenter registry study of acute bacterial skin and skin structure infection (ABSSSI) and community-acquired bacterial pneumonia (CABP) patients treated with ceftaroline fosamil in the US. Data for this analysis were collected between August 2011 and February 2013 at US study centres by randomly ordered chart review. Clinical success rates among ABSSSI patients were >81% when ceftaroline fosamil was used as first- or second-line therapy, including monotherapy and concurrent therapy. Among CABP patients, clinical success rates were >77% among first-line and second-line patients and patients who received first-line concurrent therapy or second line monotherapy or concurrent therapy. For CABP patients treated with ceftaroline fosamil as first-line monotherapy, the clinical success rate was 70%. Ceftaroline fosamil is an effective treatment option for patients with ABSSSI or CABP with similar clinical success rates when used as first-line or second-line treatment.     

Broad spectrum antibiotics in newborns increase multi-drug resistant infections.

Our objective was to determine if broad spectrum antibiotics (BSA) are associated with multi-resistant bacterial (MRB) infections in neonatal patients. We conducted a case-control study with two groups of patients: those with and without a MRB infection. We included 43 cases and 43 controls. MRB strains were: 21 S. maltophila (49%), 11 ESBL-producing Enterobacteriae (25%), 8 P. aeruginosa (19%) and 3 MRSA (7%). Odds ratio (OR) for MRB after seven days of carbapenems was 4.25 (95% confidence interval (CI) 1.4–17.4) and OR for MRB after seven days of third generation cephalosporin was 8 (95% CI 1.1–34.9). BSA longer than seven days, increases MRB infections 22.5 times in patients with bronchopulmonary dysplasia (BPD). Our data show a clear association between the use of BSA and the development of MRB infections, especially in BPD. Although we cannot state this is a causal relationship, we can recommend avoiding prolonged treatment with these antibiotics in preterm babies at risk of BPD.     

Predominance of hospital-associated MRSA among cystic fibrosis patients in a Turkish reference cystic fibrosis centre

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) strains are the major causative agents of numerous hospital- and community-acquired infections. Increasing prevalence of MRSA in cystic fibrosis (CF) populations is reported all over the world. Although there are papers reporting the prevalence and genetic backgrounds of MRSA isolates from different settings in Turkey, there is no information regarding the situation in the CF community. This study was conducted to characterize the MRSA strains recovered from CF patients followed-up at a Turkish reference CF centre. Microbiological testing of isolates was performed via conventional microbiological techniques. Molecular characterization of MRSA isolates was carried out by SCCmec typing by multiplex PCR and PVL gene determination. Among a total of 604 CF patients included in the study, 325 patients were found to harbour S. aureus (53·8%). Of those 325 patients, 24 were positive for MRSA during their follow-up (7·4%). Thirty-two MRSA isolates from these patients were chosen for further assessment of molecular characteristics. Twenty-six MRSA isolates exhibited a pattern like SCCmec type III (81·2%) and six consecutive MRSA isolates of a single patient revealed SCCmec type IV (18·7%). Our findings definitely support the need for further surveillance studies for CF-MRSA strains and highlight the need for infection control measures in the setting of CF centres.     

Evolution of Antibiotic Resistance in Gram-Positive Pathogens

Abstract

Staphylococcus aureus is a common cause of soft tissue infection, e.g. impetigo, cellulitis, or wound infection, and causes osteomyelitis, arthritis, bac-teremia with metastatic infection, and scalded skin and toxic shock syndromes. Coagulase-negative staphylococci have become increasingly important causes of nosocomial bacteremia associated with invasive monitoring, intravascular catheters and prosthetic heart valves or joints. Most staphylococci produce b-lactamase and are resistant to penicillin. An increasing proportion of S. aureus have intrinsic resistance to methicillin (MRSA) and present major problems in hospitals for the control of cross infection. The glycopeptides, teicoplanin and vancomycin, are the antibiotics of first choice for treatment of these infections.

After the first report describing a Japanese clinical isolate of vancomycin-resistant S. aureus (VRSA), several papers have documented the emergence of these microorganisms. Since the development and spreading of this phenomenon which is perceived as a fearsome threat to the already difficult therapy of nosocomial infections due to the prevalence of heterogeneous vancomycin resistance, we found the incidence of MRSA exceeds 35% in our hospital. Out of 179 methicillin-resistant S. aureus isolated during 1997-1998, two strains (1.1%) gave subclones with vancomycin MICs of 8 mg/L. PFGE showed identical restriction patterns for both isolates, suggesting transfer of a single clone between two different patients.     

Long-Term Intramuscular Teicoplanin Treatment of Chronic Osteomyelitis Due to Oxacillin-Resistant Staphylococcus aureus in Outpatients

Abstract

Oxacillin-resistant staphylococci are the most serious pathogens in chronic osteomyelitis and only glycopeptides have been shown to be efficacious against them. We assessed the safety and efficacy of a regimen of teicoplanin 400 mg/day i.m. as long-term treatment in outpatients with osteomyelitis. A total of 76 patients received teicoplanin. Twenty-five patients had chronic prosthetic osteomyelitis (20 hip) and 51 patients had osteomyelitis caused by osteo-syn-thesis devices. Oxacillin-resistant Staphylococcus aureus was isolated in pure culture in 55 patients (72%). A total of 21 patients had polymicrobial infection with a total of 48 isolated strains. All patients were treated with teicoplanin 400 mg i.m. once-a-day alone or with other drugs for a minimum of 4 months. Only one patient had side effects requiring discontinuation of treatment. The teicoplanin dose was reduced to 200 mg/day i.m. in 2 patients to decrease cre-atinine clearance values. Seventy out of 76 patients were cured.     

A prospective randomized trial comparing MVAC and CISCA chemotherapy for patients with metastatic urothelial tumors

To evaluate the relative efficacy of cisplatin, cyclophosphamide, and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) (CISCA) versus methotrexate, vinblastine, Adriamycin, and cisplatin (MVAC), a prospective randomized trial was performed in patients with advanced metastatic urothelial tumors. Patients were stratified by histologic disease type and degree of tumor dissemination. Equal distribution of the clinical characteristics was achieved. One hundred ten patients with metastatic disease of the urinary tract (86 bladder, 16 renal pelvis, seven ureter, one prostatic urethra) met eligibility criteria and were enrolled on study. These represented 82% of the total patients seen during the study period in the Section of Genitourinary Oncology who met the eligibility criteria. The combined complete and partial response rate was significantly higher for patients treated with MVAC than for those treated with CISCA (65% v 46%; P less than .05). The survival duration of MVAC-treated patients was significantly longer than that of CISCA-treated patients (mean, 62.6 weeks; median, 48.3; range, 5.0+ to 162.3+ v mean, 40.4 weeks; median, 36.1; range, 7+ to 147.1+). We conclude that MVAC chemotherapy is superior to CISCA chemotherapy, achieving a higher response rate and a longer survival for equivalent patients with metastatic urothelial tumors.     

Metronidazole Single versus Multiple Daily Dosing in Serious Intraabdominal/Pelvic and Diabetic Foot Infections

Abstract

The purpose of the study was to compare the clinical efficacy of once-daily versus multiple dose regimens of metronidazole in inpatients with serious/systemic Bacteroides fragilis infections, i.e., intraabdominal/pelvic and diabetic foot infections. A retrospective chart review was performed on 145 adult inpatients who received combination therapy with metronidazole for B. fragilis abdominal/pelvic infection or diabetic (deep) foot infections/osteomyelitis. Exclusion criteria included metronidazole given for indications other than those mentioned, patients who received only one dose of metronidazole, and patients who received oral metronidazole only. The 145 patients were in two groups: 66 patients in the metronidazole 1 g (i.v.) q24h (Group A) and 79 patients who received metronidazole 500 mg (i.v./p.o.) q6-8h dosing (Group B). Patient demographics included age, gender, indications of metronidazole, concomitant antibiotics, and co-morbidities. Data collection also included length of stay (LOS), antibiotic days, and clinical outcomes. The 145 patients in our study had a mean age of 66 years, 61% were female and 39% male. Most patients were being treated for definitive intraabdominal/pelvic infections (82%), or probable intraabdominal/pelvic infections (22%). Only 6% had deep diabetic foot infections of osteomyelitis (percentages exceed 100% since a patient can have more than one indication) and were included since B. fragilis is also an important pathogen in diabetic osteomyelitis. Group A patients had more concomitant antibiotics and co-morbidities (p <0.0001 and p <0.05 respectively, chi-square test for trend) than Group B patients. There were no statistically significant differences between groups A and B for LOS and antibiotic days (p = 0.42 and p = 0.92 respectively, by rank-sum test), but after adjusting for concomitant antibiotics and co-morbidities Group A patients had clinically shorter LOS and fewer antibiotic days. Unadjusted mortality and failure rates were non-significantly higher in group A (relative ratios of 12.1% / 6.3% = 1.91 and 18.2% / 10.1% = 1.80 respectively), but after adjusting for concomitant antibiotics and co-morbidities with stratification analysis, groups A and B were virtually the same (risk differences of ≤1% ). The authors conclude that for B. fragilis infections, as part of combination therapy, metronidazole 1 g (i.v.) q24h appears to be as efficacious and not inferior to multiply- dosed metronidazole regimens. Once daily metronidazole, i.e., 1 g (i.v.) q24h for the treatment of serious systemic infections where B. fragilis is an important co-pathogen (intraabdominal/pelvic and deep diabetic foot infections) has pharmacokinetic and pharmaco-economic advantages.     

Comparison of the efficacy of tigecycline and teicoplanin in an experimental methicillin-resistant Staphylococcus aureus osteomyelitis model

We evaluated the efficacy of tigecycline and teicoplanin in a rat model of MRSA osteomyelitis. Osteomyelitis was induced with an intramedullary injection of 10(8 )colony-forming units (cfu) of MRSA. After osteomyelitis formation was confirmed on Day 14, infected rats were randomly divided into three groups: tigecycline (n=13), teicoplanin (n=13), and no-treatment control (n=14). A 28-day antibiotic therapy with a subcutaneous injection of tigecycline (14 mg/kg twice daily) or intramuscular administration of teicoplanin (20 mg/kg daily) was administered. Rats were then sacrificed, and the tibias were harvested. The bones were weighed and then cultured. Our results indicated that bacterial growth was significantly reduced in teicoplanin and tigecycline groups, compared to the control group (p=0.019 and p=0.006, respectively). However, no difference was detected between the two antibiotic groups (p=1.000). No bacterial growth was detected in 7 out of 13 and 9 out of 13 specimens of the teicoplanin and tigecycline treated groups, respectively. Although this result was numerically in favor of tigecycline, the difference was not statistically significant (p=0.427). In conclusion, tigecycline, a novel antibiotic, appears as an effective alternative to teicoplanin in the treatment of osteomyelitis caused by MRSA.     

Bevacizumab+chemotherapy versus chemotherapy alone in elderly patients with untreated metastatic colorectal cancer: a randomized phase II trial—PRODIGE 20 study results

BackgroundMetastatic colorectal cancer frequently occurs in elderly patients. Bevacizumab in combination with front line chemotherapy (CT) is a standard treatment but some concern raised about tolerance of bevacizumab for these patients. The purpose of PRODIGE 20 was to evaluate tolerance and efficacy of bevacizumab according to specific end points in this population.Patients and methodsPatients aged 75 years and over were randomly assigned to bevacizumab + CT (BEV) versus CT. LV5FU2, FOLFOX and FOLFIRI regimen were prescribed according to investigator’s choice. The composite co-primary end point, assessed 4 months after randomization, was based on efficacy (tumor control and absence of decrease of the Spitzer QoL index) and safety (absence of severe cardiovascular toxicities and unexpected hospitalization). For each arm, the treatment will be consider as inefficient if 20% or less of the patients met the efficacy criteria and not safe if 40% or less met the safety criteria.ResultsAbout 102 patients were randomized (51 BEV and 51 CT), median age was 80 years (range 75–91). Primary end point was met for efficacy in 50% and 58% and for safety in 61% and 71% of patients in BEV and CT, respectively. Median progression-free survival was 9.7 months in BEV and 7.8 months in CT. Median overall survival was 21.7 months in BEV and 19.8 months in CT. The 36-month overall survival rate was 27% in BEV and 10.1% in CT. Severe toxicities grade 3/4 were mainly non-hematologic toxicities (80.4% in BEV, 63.3% in CT).ConclusionBevacizumab combined with CT was safe and efficient. Both arms met the primary safety and efficacy criteria.     

Frequency of Familial Colon Cancer and Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) in a Large Population Database

Background and aims: Estimates have been made concerning the fraction of colorectal cancer (CRC) cases that meet Amsterdam I criteria but not Amsterdam II criteria. The aim of this study was to determine in a population setting what fraction of CRC cases can be considered familial high-risk, what fraction of these meet Amsterdam I or II criteria, and what fraction of CRC cases overall meet Amsterdam I and II criteria. Methods: The Utah Population Data Base (UPDB), which links Utah genealogies to the Utah Cancer Registry, was used to examine the aims of the study. Familial high-risk was operationally defined as CRC occurring at an age <50 years or as a part of a first-degree relative pair. A subset of Amsterdam positive cancers was tested for microsatellite instability (MSI) to determine what fraction of Amsterdam families was likely to have hereditary nonpolyposis colorectal cancer (HNPCC). Results: Of the 6,628 CRC cases in the UPDB, 24.5% met the criteria for familial high-risk. Of these, 2.6% met Amsterdam I criteria and 5.5% Amsterdam II. Of total data base CRC cases, 0.8% met Amsterdam I criteria and 2.3% Amsterdam II. In a subset of colon tumors from Amsterdam families, 70% were MSI stable. Conclusions: Although nearly 25% of CRC cases in our population data base met a simple definition of familial high-risk, only a small fraction of these and a smaller fraction of total CRC cases met Amsterdam I or II criteria. Less than half of a limited set of tumors from Amsterdam families were MSI positive.     

Utilization Patterns of Single Fraction Radiation Therapy for Multiple Myeloma

BackgroundPatients with multiple myeloma (MM) are living longer than ever before thanks to new therapies. As a consequence, radiation therapy (RT) is increasingly important in the management of bone lesions from MM. Current American Society for Radiation Oncology guidelines recommend greater usage of 8 Gy in 1 fraction for treatment of these lesions. The objective of this study is to analyze utilization of 8 Gy in 1 fraction for treatment of MM bone lesions in the United States utilizing the National Cancer Data Base (NCDB).Materials and MethodsThe NCDB was used to identify patients with MM treated with palliative RT for painful bony lesions in the period between 2004 and 2014. Utilization rate of RT in this patient population as well as single-fraction (SFRT) versus multiple-fraction RT (MFRT) was compared according to demographic, socioeconomic, and logistic details.ResultsA total of 95,190 patients met our inclusion criteria. Of these, 10,261 (10.8%) patients received RT, and a total of 243 (2.4%) of these patients received SFRT over the 10-year period. There was an 11.73% annual increase (P = .0001) in SFRT utilization from 2004 to 2014. Older age, black race, longer distance from the treatment facility, lower degree of education, treatment at an academic or integrated healthcare network, worse comorbidities, and more recent diagnoses were all associated with increased usage of SFRT.ConclusionSFRT for the management of MM painful bony metastases remains underutilized. Trends show that radiation oncologists do not appear to be changing their approach to treating this disease.     

Soft tissue sarcoma presenting with metastatic disease

BACKGROUND:

The objective of this study was to assess patient, tumor, and treatment factors that affected overall survival in a group of patients who underwent surgery for soft tissue sarcoma (STS) and presented with American Joint Commission on Cancer stage IV disease.

METHODS:

A retrospective review was undertaken of a single institution's database from the years 1986 to 2006 in all patients who met the following inclusion criteria: 1) surgical management of the primary tumor was undertaken, and 2) metastatic disease was present at the time of initial presentation. In total, 112 patients were identified who met the inclusion criteria.

RESULTS:

The 5‐year survival rate for the entire group was 17%. In univariate analysis, the variables that were identified as statistically significant for predicting improved overall survival were resection of metastatic disease (P = .003), <4 pulmonary metastases (P = .05), and the presence of lymph node metastases versus pulmonary metastases (P = .0002). In multivariate analysis, only the presence of lymph node metastases versus pulmonary metastases retained statistical significance (P = .05). The 5‐year survival rate for patients who had lymph nodes metastases at diagnosis was 59%, whereas it was only 8% for patients who presented with pulmonary metastases.

CONCLUSIONS:

Patients who presented with metastatic STS had a very poor prognosis despite aggressive surgical management of their primary tumor. The current results indicated that, although patients with isolated lymph node metastases may be cured by surgical resection, patients with pulmonary metastases are unlikely to be cured even with aggressive surgical management and should be treated with palliation of symptoms as the main objective. Cancer 2011. © 2010 American Cancer Society.     

EGFR-TKIs plus local therapy demonstrated survival benefit than EGFR-TKIs alone in EGFR-mutant NSCLC patients with oligometastatic or oligoprogressive liver metastases

To investigate whether addition of local therapy to EGFR-TKIs could provide survival benefit than EGFR-TKIs alone in EGFR-mutant NSCLC patients with oligometastatic or oligoprogressive liver metastases (LM). Patients with EGFR-mutant NSCLC and oligometastatic or oligoprogressive LM who met inclusion criteria were retrospectively identified. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS) and patterns of failure. Addition of local therapy was associated with a significantly longer PFS (13.8 vs. 8.6 m, p <0.001) and OS (31.2 vs. 18.5 m, p <0.001) in whole group. In oligometastatic cohort, 20 patients received EGFR-TKIs and 23 received EGFR-TKIs plus local therapy as first-line treatment. Addition of local therapy showed a significantly longer PFS (12.9 vs. 7.9 m, p = 0.041) and OS (36.8 vs. 21.3 m, p = 0.034) than EGFR-TKIs alone. In oligoprogressive cohort, 24 patients received continuation of EGFR-TKIs plus local therapy and 25 received switching chemotherapy. Median PFS2 (13.9 vs. 9.2 m, p = 0.007) and OS (28.3 vs. 17.1 m, p = 0.011) was significantly longer in combined group than in switching chemotherapy group. Distant metastatic sites progression was the major pattern of failure in combined group while locoregional recurrence was the major reason in monotherapy or switching chemotherapy group. Our study suggested that EGFR-TKIs plus local therapy showed prolonged survival benefit than EGFR-TKIs alone in EGFR-mutant NSCLC patients with oligometastatic or oligoprogressive LM, indicating addition of local therapy would be alternative choice in this clinical scenario.     

mecA-positive methicillin-sensitive Staphylococcus aureus clinical isolates in Zenica-Doboj Canton,Bosnia and Herzegovina

Forty-four mecA-positive and eight mecA-negative Staphylococcus aureus isolates confirmed by PCR were further tested by disc-diffusion (DD) oxacillin and cefoxitin, oxacillin Epsilon (E)-test, and oxacillin and cefoxitin minimal inhibitory concentration (MIC) Strip methicillin-resistant phenotype in S. aureus (MRSA) tests. Among 44 mecA-positive S. aureus isolates, two (4·5%) were detected as MRSA by DD-oxacillin, 17 (38·6%) by DD-cefoxitin test, and seven (15·9%) by the E-test. In the cefoxitin MIC Strip MRSA test, 19 (43·2%) isolates were resistant. In the oxacillin MIC Strip MRSA test, 18 (40·9%) isolates were resistant and 26 (59·1%) were sensitive, i.e. oxacillin-sensitive MRSA (OS-MRSA) (MIC range 0·25-≤0·25 mg/l). Fifteen out of 26 OS-MRSA (57·7%) belonged to spa-CC 355/595, 78% of which belonged to the largest PFGE clone. Some discrepancies between the phenotypic methods for MRSA identification obtained in this study were caused by large proportion of OS-MRSA. Misidentification of OS-MRSA as MSSA might result in an appearance of highly resistant MRSA in patients treated with beta-lactam antibiotics.     

The Effectiveness and Safety of Oral Linezolid for the Primary and Secondary Treatment of Osteomyelitis

Abstract

The pharmacokinetic profile of oral linezolid makes it an attractive alternative for the treatment of osteomyelitis. Few studies have described the efficacy of linezolid in the treatment of osteomyelitis. A retrospective, observational analysis was conducted at Edward Hines, Jr. VA Hospital. Patients who received oral linezolid from June 2000 to December 2002 were identified from pharmacy records. Fortytwo patients who received oral linezolid for osteomyelitis at our institution were identified. Only patients who had received at least six weeks of linezolid therapy were evaluated for clinical effectiveness. Patients were also evaluated for adverse drug reactions due to linezolid.

The clinical cure rate was 55% for the 20 patients who received at least six weeks of therapy. Adverse events included gastrointestinal disturbances (15%), thrombocytopenia (10%), anemia (10%), neutropenia (5%) and rash (5%).

The authors conclude that oral linezolid is an alterative to intravenous antibiotics for the treatment of osteomyelitis.