Individualized significance of the -251 A/T single nucleotide polymorphism of interleukin-8 in severe infections.

Based on the concept of the individualized nature of sepsis, we investigated the significance of the -251 A/T (rs4073) single nucleotide polymorphism (SNP) of interleukin (IL)-8 in relation to the underlying infection. Genotyping was performed in 479 patients with severe acute pyelonephritis (UTI, n = 146), community-acquired pneumonia (CAP, n = 109), intra-abdominal infections (IAI, n = 119), and primary bacteremia (BSI, n = 105) by restriction fragment length polymorphism of the polymerase chain reaction (PCR) product and compared with 104 healthy volunteers. Circulating IL-8 was measured within the first 24 h of diagnosis by an immunosorbent assay. Carriage of the AA genotype was protective from the development of UTI (odds ratio 0.38, p: 0.007) and CAP (odds ratio 0.30, p: 0.004), but not from IAI and BSI. Protection from the development of severe sepsis/septic shock was provided for carriers of the AA genotype among patients with UTI (odds ratio 0.15, p: 0.015). This was accompanied by greater concentrations of circulating IL-8 among patients with the AA genotype. It is concluded that carriage of rs4073 modifies susceptibility for severe infection in an individualized way. This is associated with a modulation of circulating IL-8.

The course of spinal tuberculosis (Pott disease): results of the multinational, multicentre Backbone-2 study.

We aimed to describe clinical, laboratory, diagnostic and therapeutic features of spinal tuberculosis (ST), also known as Pott disease. A total of 314 patients with ST from 35 centres in Turkey, Egypt, Albania and Greece were included. Median duration from initial symptoms to the time of diagnosis was 78 days. The most common complications presented before diagnosis were abscesses (69%), neurologic deficits (40%), spinal instability (21%) and spinal deformity (16%). Lumbar (56%), thoracic (49%) and thoracolumbar (13%) vertebrae were the most commonly involved sites of infection. Although 51% of the patients had multiple levels of vertebral involvement, 8% had noncontiguous involvement of multiple vertebral bodies. The causative agent was identified in 41% of cases. Histopathologic examination was performed in 200 patients (64%), and 74% were consistent with tuberculosis. Medical treatment alone was implemented in 103 patients (33%), while 211 patients (67%) underwent diagnostic and/or therapeutic surgical intervention. Ten percent of the patients required more than one surgical intervention. Mortality occurred in 7 patients (2%), and 77 (25%) developed sequelae. The distribution of the posttreatment sequelae were as follows: 11% kyphosis, 6% Gibbus deformity, 5% scoliosis, 5% paraparesis, 5% paraplegia and 4% loss of sensation. Older age, presence of neurologic deficit and spinal deformity were predictors of unfavourable outcome. ST results in significant morbidity as a result of its insidious course and delayed diagnosis because of diagnostic and therapeutic challenges. ST should be considered in the differential diagnosis of patients with vertebral osteomyelitis, especially in tuberculosis-endemic regions. Early establishment of definitive aetiologic diagnosis and appropriate treatment are of paramount importance to prevent development of sequelae.

Impact of haplotypes of TNF in the natural course of infective endocarditis.

Based on previous findings for the role of single nucleotide polymorphisms (SNPs) of TNF for the predisposition for bloodstream infections, this study investigates the role of these SNPs at the promoter positions -376, -308, -238 in infective endocarditis (IE). In a case-control study, 83 patients with IE and 83 controls were enrolled. Blood genotyping for the presence of G or A alleles of the three SNPs was carried out using restriction fragment length polymorphisms. Haplotypes were calculated. Patients were mostly infected by Staphylococcus aureus (32.5%) and by species of enterococci (14.3%) and streptococci (14.3%). Carriage of the minor frequency A alleles at -238 of the promoter region of TNF was greater than in controls (8.4% versus 1.2%, p 0.003). The presence of any of the three GGA/GAA/AGA haplotypes was more frequent in patients with IE (OR 8.22, 95CI% 1.8-37.4, p 0.001). After multivariate logistic regression analysis, it was found that the only factor related to fatal outcome was carriage of the wild-type GGG haplotype (OR, 3.29, 95CI%, 1.05-10.29, p 0.04). GGA, AGA and GAA haplotypes were more frequent in patients with IE than in controls, suggesting a predisposition for IE and a potential protective role against fatal outcome, as the wild-type GGG haplotype was independently related with death.

Dispensing of antibiotics without prescription in Greece, 2008: another link in the antibiotic resistance chain.

Antibiotic resistance has been associated with the use of antibiotics. The dispensing of antimicrobials without prescription is a potential source of inappropriate antibiotic use. In our study, antibiotics were requested without prescription from pharmacies in the metropolitan area of Athens in Greece in 2008. Twenty-one collaborators visited 174 pharmacies and asked for either amoxicillin/clavulanate acid or ciprofloxacin without providing a prescription or any other justification for the request. In Greece additional restrictions for fluoroquinolone prescriptions were implemented in 2003 after which a separate specific prescription form needs to be filled in by the prescriber, justifying the choice of any fluoroquinolone. Amoxicillin/clavulanate acid was dispensed in all cases. Furthermore, despite the regulation restricting the prescription of ciprofloxacin, this drug was dispensed by 53% of the pharmacies. It appears that the implementation of measures to restrict the use of certain antibiotics (e.g. ciprofloxacin that was studied in our case) was effective in reducing, although not eliminating, inappropriate dispensing. Overall, dispensing of antimicrobials without prescription is a widespread practice in the studied area and is contributing to the overuse of antibiotics.

Efficacy and tolerability of linezolid in chronic osteomyelitis and prosthetic joint infections: a case-control study.

Clinical experience of prolonged use of linezolid in patients with bone infections is accumulating. However more efficacy and safety data are required. this is a case-control study of patients who received linezolid for difficult-to-treat, intolerant or resistant-to-other-antibiotics bone infections. Linezolid was administered i.v. or orally in 34 patients. Results concerning efficacy and safety were compared to a group of well-matched controls. The clinical arrest rate was 74% in the linezolid group and 68% in the control group (p=NS). treatment was discontinued in 14 (44%) patients of the linezolid group and in 2 (6%) patients of the control group due to adverse events. In the linezolid group 11 (33%) patients developed anemia and 3 (9%) developed thrombocytopenia that led to discontinuation of treatment. Linezolid is effective in a substantial proportion of patients, but the incidence of hematologic adverse events makes close follow-up and laboratory monitoring mandatory.

In vitro activity of daptomycin against Gram-positive cocci: the first multicentre study in Greece.

A total of 10420 Gram-positive cocci (including staphylococci, enterococci and various groups of streptococci) collected from clinically significant specimens in ten Greek hospitals during 2006--2007 were tested for their susceptibility to daptomycin. The minimum inhibitory concentration (MIC) was determined by the broth microdilution method. Daptomycin demonstrated very high activity against Enterococcus faecalis (MIC at which 50% of the isolates were inhibited (MIC50) = 1mg/L and MIC at which 90% of the isolates were inhibited (MIC90) = 1.36 mg/L), Enterococcus faecium (MIC50 = 1.36 mg/L and MIC90 = 1.90 mg/L), Streptococcus pyogenes (MIC50 = 0.12 mg/L and MIC90 = 0.50mg/L), Streptococcus agalactiae (MIC50 = 0.09 mg/L and MIC90 = 0.12 mg/L), Streptococcus pneumoniae (MIC50 = 0.24 mg/L and MIC90 = 0.5 mg/L) and viridans group streptococci (MIC50 = 0.50 mg/L and MIC90 = 0.89 mg/L). Resistance to linezolid and vancomycin for enterococci and to penicillin for streptococci appears to be independent of reduced susceptibility to daptomycin. On the other hand, daptomycin was also active against meticillin-resistant Staphylococcus aureus (MIC50 = 0.44 mg/L and MIC90 = 0.78 mg/L) and meticillin-resistant coagulase-negative staphylococci (MIC50 = 0.24 mg/L and MIC90 = 0.44 mg/L); however, 0.9% of the staphylococci tested had an MIC > 1mg/L, which is the Clinical and Laboratory Standards Institute breakpoint proposed for susceptibility. For all tested organism groups, resistance to daptomycin was not associated with glycopeptide resistance.

Pharmacokinetics of fusidic acid and cefepime in heart tissues: implications for a role in surgical prophylaxis.

The pharmacokinetic profiles of fusidic acid and cefepime in heart tissues were assessed in 30 patients undergoing elective valve replacement and cardiopulmonary bypass. Single doses of 1 g of fusidic acid and 2 g of cefepime were administered intravenously to two groups of 15 and 15 patients respectively upon initiation of anesthesia. Samples of serum, heart valves, myocardium, pericardium, mediastinal fat and sternum were collected within <1 hour, 1-2 h and 2-4 h after the end of drug infusion. Drug concentrations were estimated by a microbiological assay. It was found that concentrations of fusidic acid in all specimens were 20-fold higher than the MIC90s of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis, being at such levels throughout all period of sampling. Cefepime concentrations in heart valves collected 1-2 h after drug infusion were higher than the MIC90s of multidrug-resistant Enterobacteriaceae. It is concluded that both fusidic acid and cefepime penetrated heart tissues adequately; however only fusidic acid could also accumulate in the mediastinum. These data suggest that both antibiotics may be a good alternative for prophylaxis in open heart surgery.

Nosocomial vs. community-acquired infective endocarditis in Greece: changing epidemiological profile and mortality risk.

Current epidemiological trends of infective endocarditis (IE) in Greece were investigated via a prospective cohort study of all cases of IE that fulfilled the Duke criteria during 2000-2004 in 14 tertiary and six general hospitals in the metropolitan area of Athens. Demographics, clinical data and outcome were compared for nosocomial IE (NIE) and community-acquired IE (CIE). NIE accounted for 42 (21.5%) and CIE for 153 (78.5%) of 195 cases. Intravenous drug use was associated exclusively with CIE, while co-morbidities (cardiovascular disease, diabetes mellitus, chronic renal failure requiring haemodialysis and malignancies) were more frequent in the NIE group (p <0.05). Prosthetic valve endocarditis (PVE) predominated in the NIE group (p 0.006), and >50% of NIE cases had a history of vascular intervention. Coagulase-negative staphylococci and enterococci were more frequent in cases of NIE than in cases of CIE (26.2% vs. 5.2%, p <0.01, and 30.9% vs. 16.3%, p 0.05, respectively). Enterococci accounted for 19.5% of total IE cases and were the leading cause of NIE. Staphylococcus aureus IE was hospital-acquired in only 11.9% of cases. In-hospital mortality was higher for NIE than for CIE (39.5% vs. 18.6%, p 0.02). Cardiac failure (New York Heart Association grade III-IV; OR 13.3, 95% CI 4.9-36.1, p <0.001) and prosthetic valve endocarditis (OR 3.7, 95% CI 1.3-10.6, p 0.01) were the most important predictors of mortality.

Characteristics and regional variations of group D streptococcal endocarditis in France.

The proportion of infective endocarditis (IE) caused by group D streptococci (GDS; formerly Streptococcus bovis) increased markedly in France, to account for 25% of all cases of IE by 1999. In an attempt to explain this phenomenon, a comparative analysis of GDS and oral streptococci (OS) causing IE was performed. This study was based on data collected from a large cross-sectional population-based survey that was conducted in 1999. In total, 559 cases of definite IE were recorded, of which 142 involved GDS and 79 involved OS. Patients with GDS IE were older (62.7 vs. 56.6 years, p 0.01) and had a history of valve disease less frequently than did patients with OS IE (33.8% vs. 67.1%, p <0.0001). At-risk procedures for IE were performed less frequently in patients with GDS than in patients with OS (14.8% vs. 24.1%, p 0.08), but co-morbidities were more frequent in the GDS group (59.9% vs. 32.9%, p 0.0001). Diabetes, colon diseases and cirrhosis were also more frequent in the GDS group (p 0.006, p <0.0001 and p 0.08, respectively). Rural residents accounted for 31.0% of the GDS group, but for only 15.2% of the OS group (p 0.001). Likewise, the proportion of GDS IE was higher in regions with mixed (urban and rural) populations (Franche-Comté 81.8%, Marne 68.7%, Lorraine 70.3% and Rhône-Alpes 65.3%) than in exclusively urban regions (Paris and Ile de France 58.0%). Further investigations are required to elucidate the link in France between the incidence of GDS IE, rural residency and nutritional factors.

No effect of pyridoxine on the incidence of myelosuppression during prolonged linezolid treatment.

Complications of long-term linezolid administration include anemia and thrombocytopenia. A recent report has suggested that pyridoxine may prevent myelosuppression. Pyridoxine was administered to 24 patients with bone infections who were being treated with linezolid. Thrombocytopenia occurred in 11 patients (45.8%), and anemia occurred in 6 (25%). We concluded that treatment wtih pyridoxine is unlikely to benefit patients who have been receiving linezolid for >2 weeks.