Oral fosfomycin for the treatment of chronic bacterial prostatitis.

BACKGROUND: Chronic bacterial prostatitis (CBP) is a difficult-to-treat infection as only a few antibiotics achieve therapeutic concentrations in the prostate. Data on the efficacy and safety of oral fosfomycin for the treatment of CBP are limited. OBJECTIVES: To analyse the efficacy and safety of fosfomycin in CBP due to MDR pathogens. METHODS: In a prospective observational study, an oral regimen of 3 g of fosfomycin q24h for 1 week followed by 3 g q48h for a treatment duration of 6-12 weeks was administered. The outcome was clinical and microbiological cure rate at the end of treatment (EOT) and rate of relapse at 3 and 6 months. RESULTS: The study included 44 patients. The most common pathogen was Escherichia coli (66%), followed by Klebsiella spp. (14%) and Enterococcus faecalis (14%). Most strains were MDR (59%) and 23% had an ESBL phenotype; 33 of 44 strains were resistant to fluoroquinolones, but all were susceptible to fosfomycin (median MIC for Gram-negative pathogens 1.5 mg/L). In 25 patients, treatment was administered for 6 weeks, whereas in the remaining 19 patients it was prolonged to 12 weeks based on the presence of calcifications in the prostate. Cure rate was 82% at EOT and 80% and 73% at 3 and 6 months accordingly. Microbiological eradication was achieved in 86% and 77% at EOT and at 6 months, respectively. Failure was observed in 12 patients. The most common adverse event was diarrhoea (18%). CONCLUSIONS: Oral fosfomycin, particularly in the era of MDR prevalence, represents an attractive, safe and effective alternative to fluoroquinolones for the treatment of CBP.

Challenge for higher colistin dosage in critically ill patients receiving continuous venovenous haemodiafiltration.

Traditionally, reduced daily doses of colistin methanesulphonate (CMS) in critically ill patients receiving continuous venovenous haemodiafiltration (CVVHDF) have resulted in suboptimal colistin concentrations. The necessity of a loading dose (LD) at treatment initiation has been proposed. A LD of 9 million IU (MU) [ca. 270 mg of colistin base activity (CBA)] was administrated with a maintenance dose of 4.5 MU (ca. 140 mg CBA) every 12 h (q12h) to eight critically ill patients receiving renal replacement therapy. Blood samples were collected immediately before and at different time intervals after the LD and the fourth dose, whilst pre-filter and post-filter blood samples were also collected. CMS and colistin concentrations were determined using an LC-MS/MS assay. Median maximum observed concentrations after the LD were 22.1 mg/L for CMS and 1.55 mg/L for colistin, whereas during maintenance dosing the corresponding values were 12.6 mg/L and 1.72 mg/L, respectively. CVVHDF clearance was determined as 2.98 L/h for colistin, equivalent to 62% of total apparent colistin clearance in CVVHDF patients. Both CMS and colistin were cleared by CVVHDF. Application of a LD of 9 MU CMS resulted in more rapid achievement of the target colistin concentration. Following implementation of a predicted pharmacokinetic model on plasma CMS/colistin concentrations, a LD of 12 MU CMS appears more appropriate, whilst a CMS maintenance dosage of at least 6.5-7.5 MU q12h is suggested in patients undergoing CVVHDF. However, further clinical studies are warranted to assess the safety of a LD of 12 MU CMS in patients receiving CVVHDF.

Nationwide surveillance of resistance rates of Staphylococcus aureus clinical isolates from Greek hospitals, 2012-2013.

Purpose To evaluate the in vitro efficacy of several anti-staphylococcal agents against a nationwide collection of contemporary Staphylococcus aureus clinical isolates from several healthcare centres in Greece. Methods Thirty hospitals throughout Greece (18 in Attica) provided all clinical isolates of S.aureus from April 2012 to May 2013 to a central lab to be re-submitted to susceptibility testing. The MICs were evaluated by Vitek® 2 with the exception of ceftaroline (OXOID M.I.C. Evaluator™). Vancomycin and daptomycin MICs were also evaluated by Etest®. Heterogeneously vancomycin-intermediate strains (hVISA) were detected by the Etest® GRD. VISA phenotype was confirmed by PAP-AUC. Results A total of 1005 isolates (39% MRSA) were studied. Susceptibility rates were: erythromycin 66.5%, clindamycin 79.2%, SXT 98.9%, rifampicin 97.3%, fusidic acid 67%, moxifloxacin 78.8%, vancomycin 99.9%, ceftaroline 92.9% and linezolid, tigecycline and daptomycin 100%. For mupirocin, high level resistance could be excluded for 98.9% of isolates. Vancomycin Etest® MIC50/90 were 1.5/1.5 mg/L, 58.5% of isolates exhibited a MIC > 1 and 8.7% a MIC of 2 mg/L, while Vitek® MIC50/90 were 1/1 and 3.1% showed MIC > 1 mg/L. One VISA strain was detected. Among the selected 175 isolates that were screened for hVISA phenotype, six (3.4%) were positive. In 315 bloodstream isolates, 64.1% had a vancomycin Etest® MIC > 1 mg/L. Conclusions This multi-centre surveillance study revealed that a significant percentage of contemporary S.aureus isolates from Greek patients have a vancomycin MIC (> 1 mg/L) that may compromise the clinical efficacy of the drug for the treatment of serious infections. The in vitro activity of SXT, rifampicin, mupirocin, linezolid, tigecycline, daptomycin and ceftaroline remains excellent.

Promoting prudent use of antibiotics: the experience from a multifaceted regional campaign in Greece.

BACKGROUND: Antibiotic resistance, a major public health problem, has been linked to antibiotic consumption. In Greece both consumption and resistance rates are among the highest in Europe. A multifaceted campaign targeting both physicians and parents of school children was implemented for the first time in order to educate the public and update doctors, aiming to promote judicious use of antibiotics and hopefully decrease its consumption. METHODS: The programme consisted of a public education campaign and academic detailing of primary care physicians in the district of Corinth in Peloponnese. The experience and perceptions of parents were recorded in the meetings in the form of course evaluation and assessment, anonymous questionnaires. The use of Rapid Antigen Detection Test (RADT) for streptococcal pharyngitis by primary care physicians was also assessed by use of anonymous questionnaires. Antibiotic consumption was compared before and after the programme between the district of Corinth and the other districts of Peloponnese, as well as at a national level. RESULTS: Antibiotic consumption remained unaltered at 26 Defined daily doses per 1000 Inhabitants per Day (DID) in accordance with the trend in other regions and at a national level. However, the utilization of Amoxycillin and Penicillin was increased by 34.3%, while the use of other antimicrobial classes including macrolides, cephalosporins and fluoroquinolones decreased by 6.4-21.9%. The use of RADT did not lead to a significantly decreased antimicrobial consumption. CONCLUSIONS: A multifaceted educational programme targeting both the general public and primary care physicians was associated with rationalization in the choice of antimicrobial. A reduction in the total antimicrobial consumption was not achieved.

Successful treatment of extensively drug-resistant Acinetobacter baumannii ventriculitis and meningitis with intraventricular colistin after application of a loading dose: a case series.

Treatment results of six post-neurosurgical ventriculitis and meningitis cases caused by extensively drug-resistant Acinetobacter baumannii after application of an intraventricular loading dose of 500000 IU (40 mg) of colistin followed by a dose of 125000-250000 IU (10-20 mg) every 24-48 h plus parenteral colistin are reported. Simultaneous bacteraemia with an identical Acinetobacter strain was observed in three patients. The mean duration of treatment was 17.2 days (range 15-21 days) and the median time of sterilisation of cerebrospinal fluid was 2.5 days (range 1-5 days). All patients were cured, however one patient presented with chemical meningitis and one with chemical ventriculitis, conditions that clinically and biochemically resemble bacterial meningitis.

Intraventricular and intrathecal colistin as the last therapeutic resort for the treatment of multidrug-resistant and extensively drug-resistant Acinetobacter baumannii ventriculitis and meningitis: a literature review.

Acinetobacter baumannii ventriculitis/meningitis due to the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains has become a clinical entity of considerable importance in recent years. A review of the available literature regarding intraventricular (IVT) or intrathecal (ITH) administration of colistin in MDR and XDR A. baumannii ventriculitis/meningitis was conducted and a total of 83 episodes in 81 patients were identified (71 cases in adults and 10 in children and neonates). Colistin was administered via the IVT and ITH route in 52 and 22 cases, respectively, whilst in 7 cases the exact route was not identified. The median dose of local colistin was 125000 IU (10mg) with a range of 20000 IU (1.6 mg) to 500000 IU (40 mg) in adults, whilst a dose of 2000 IU/kg (0.16 mg/kg) up to 125000 IU (10mg) was used in the paediatric population. The median duration of treatment of IVT/ITH polymyxin E was 18.5 days, whilst the median time to achieve sterilisation of cerebrospinal fluid was 4 days. The rate of successful outcome was 89%, and toxicity related to treatment mainly manifested as reversible chemical ventriculitis/meningitis was reported in nine cases (11%). Nowadays, IVT and ITH colistin represents the last resort treatment of MDR and XDR A. baumannii ventriculitis/meningitis, offering a unique, rather safe and successful mode of therapy.

Effectiveness of a double-carbapenem regimen for infections in humans due to carbapenemase-producing pandrug-resistant Klebsiella pneumoniae.

Ertapenem plus doripenem or meropenem were given in three patients suffering from pandrug-resistant, KPC-2-positive Klebsiella pneumoniae bacteremia (2 patients) and urinary tract infection (1 patient), respectively. All responded successfully, without relapse at follow-up. The results obtained should probably be attributed to ertapenem's increased affinity for the carbapenemases hindering doripenem/meropenem degradation in the environment of the microorganism.

Association of Mal/TIRAP S180L variant polymorphism with decreased infection risk in patients with advanced HIV-1 infection.

OBJECTIVES: MyD88 adaptor-like (Mal/TIRAP) is an adaptor protein bridging activation of Toll-like receptors 2 and 4 after stimulation by exogenous and endogenous ligands. We investigated the association between the presence of the S180L SNP of Mal and the risk of severe infection in individuals with human immunodeficiency virus (HIV)-1 infection. METHODS: The SNP S180L was determined in a cohort of 179 HIV-1 infected Greek patients. Analysis of the prevalence of this SNP in relation to the infectious complications was evaluated. RESULTS: One hundred and thirty-two (73.3%) patients were bearing the wild type haplotype, 43 (24%) were heterozygous for the SNP, and four (2.2%) were homozygous for the variant allele. The individuals with a nadir CD4 count <200 cells/mm(3) who carried the 180L variant demonstrated a 4-fold decrease in the odds ratio (OR) for any serious infection compared with those who carried the wild-type 180S genotype (OR 0.58 vs OR 2.6, p=0.016). CONCLUSIONS: This study suggest a protection effect of the Mal S180L SNP against serious infections in HIV-1 infected individuals with low CD4 cell counts.

Association of toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms with increased infection risk in patients with advanced HIV-1 infection.

BACKGROUND. The Toll-like receptor 4 (TLR4) is an essential component of the innate immune response to various microorganisms. We investigated the association between TLR4 polymorphism and the risk of acquiring severe infections, in patients with human immunodeficiency virus (HIV)-1 infection. METHODS. The presence of TLR4 Asp299Gly and Thr399Ile single nucleotide polymorphisms (SNPs) was determined in a cohort of 199 HIV-1 infected patients and evaluated in relation to the occurrence of various infections. RESULTS. One hundred seventy-two patients were homozygous for the wild-type genotype; 22 patients (11%) were heterozygous for both SNPs; 4 were heterozygous for 1 polymorphism; 1 patient was heterozygous for the Asp299Gly SNP and homozygous for the Thr399Ile SNP. Of individuals with a nadir CD4 cell count of <100 cells/mm(3), those who carried both SNPs, compared with those who carried the wild-type genotype, demonstrated a >3-fold increase in the odds ratio (OR) of any serious infection (OR, 6.33 vs OR, 1.83, P = .043). CONCLUSIONS. This study suggests an association between the presence of TLR4 Asp299Gly and Thr399Ile polymorphisms and the occurrence of serious infections in HIV-1 infected patients with a history of nadir CD4 cell count of <100 cells/mm(3).

Colonisation with vancomycin- and linezolid-resistant Enterococcus faecium in a university hospital: molecular epidemiology and risk factor analysis.

During a hospital-wide prospective point prevalence survey of faecal carriage and environmental colonisation of vancomycin-resistant enterococci in a tertiary care university hospital in Athens (Greece), five clinical and one environmental isolate from a light switch (all in the haematology ward) were identified as vancomycin- and linezolid-resistant vanA-positive Enterococcus faecium (VLRE). The studied isolates exhibited a linezolid minimum inhibitory concentration of 12microg/mL and carried at least one mutated copy of the 23S rRNA gene, as shown by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis to detect the G2576T mutation. The enterococcal surface protein (esp) gene was detected by PCR in all isolates. Molecular typing with pulsed field gel electrophoresis (PFGE) showed that the environmental and four of the five clinical isolates were genetically related. None of the colonised patients were previously exposed to linezolid, although heavy linezolid use was noted in the institution. A case-control study was performed to assess risk factors for VLRE colonisation. In univariate analysis, immunodeficiency, underlying haematological malignancy, duration of any antimicrobial treatment before VLRE isolation, and hospitalisation in the haematology ward were pointed out as possible risk factors. A multidisciplinary approach including intensified hand hygiene, patient contact isolation, disinfection of the inanimate environment and antibiotic restriction resulted in early containment of the VLRE colonisation outbreak.

Successful treatment with moxifloxacin of experimental aortic valve endocarditis due to methicillin-resistant Staphylococcus aureus (MRSA).

Moxifloxacin (MXF) is an 8-methoxyquinolone with high activity against Gram-positive bacteria. In an experimental model of aortic valve endocarditis (EAVE), the efficacy of MXF was evaluated against a strain of methicillin-resistant Staphylococcus aureus (MRSA). Rabbits with catheter-induced aortic valve vegetations were randomly assigned to a control group or to groups receiving MXF 20 mg/kg intravenous (i.v.) twice a day (bid) or vancomycin (VAN) 30 mg/kg i.v. bid for a total of eight doses (4 days). Rabbits were sacrificed 15 h after the last dose of antibiotics. In another group, treatment with MXF was extended to 5 days and rabbits were sacrificed 5 days after the last dose (10th dose) of MXF in order to detect possible relapses of endocarditis after the end of treatment (test-of-cure (TOC) study). Both MXF and VAN significantly reduced the bacterial load in vegetations (P < 0.001 vs. controls). All animals in the MXF-TOC group had sterile vegetations. MXF given at a dose of 20 mg/kg i.v. bid for 4 days was equally effective as VAN in the treatment of EAVE due to MRSA. When treatment with MXF was extended to 5 days, the cure rate reached 100% and no relapses of endocarditis were observed.

Successful moxifloxacin prophylaxis against experimental streptococcal aortic valve endocarditis.

OBJECTIVES: Studies related to the prophylactic efficacy of fluoroquinolones against infective endocarditis are scarce. The aim of this study was to evaluate the efficacy of moxifloxacin, a quinolone active in vitro against Gram-positive cocci, in preventing streptococcal aortic valve endocarditis. METHODS: Non-bacterial thrombotic endocarditis of the aortic valve was induced by the insertion of a polyethylene catheter. Twenty-four hours later, rabbits were randomly assigned to a control group, and groups receiving either two doses of ampicillin (40 mg/kg, intravenously), 2 h apart, or a single dose of moxifloxacin (15 mg/kg, intravenously). Ampicillin and moxifloxacin were administered 0.5 and 1 h, respectively, prior to the intravenous inoculation of 10(7) cfu of Streptococcus oralis. RESULTS: Eighty-nine percent of the control animals developed infected vegetations. In rabbits challenged with this very high inoculum, moxifloxacin and ampicillin prevented endocarditis in 80% (P < 0.001 versus controls) and in 50% (P = 0.022 versus controls) of animals, respectively. The difference between ampicillin and moxifloxacin was not statistically significant (P = 0.128). CONCLUSIONS: Moxifloxacin was at least as effective as ampicillin in preventing streptococcal endocarditis.