Ceftazidime/avibactam in the era of carbapenemase-producing Klebsiella pneumoniae: experience from a national registry study.

BACKGROUND: Infections caused by KPC-producing Klebsiella pneumoniae (Kp) are associated with high mortality. Therefore, new treatment options are urgently required. OBJECTIVES: To assess the outcomes and predictors of mortality in patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam with an emphasis on KPC-Kp bloodstream infections (BSIs). METHODS: A multicentre prospective observational study was conducted between January 2018 and March 2019. Patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam were included in the analysis. The subgroup of patients with KPC-Kp BSIs treated with ceftazidime/avibactam was matched by propensity score with a cohort of patients whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam with in vitro activity. RESULTS: One hundred and forty-seven patients were identified; 140 were infected with KPC producers and 7 with OXA-48 producers. For targeted therapy, 68 (46.3%) patients received monotherapy with ceftazidime/avibactam and 79 (53.7%) patients received ceftazidime/avibactam in combination with at least another active agent. The 14 and 28 day mortality rates were 9% and 20%, respectively. The 28 day mortality among the 71 patients with KPC-Kp BSIs treated with ceftazidime/avibactam was significantly lower than that observed in the 71 matched patients, whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam (18.3% versus 40.8%; P = 0.005). In the Cox proportional hazards model, ultimately fatal disease, rapidly fatal disease and Charlson comorbidity index ≥2 were independent predictors of death, whereas treatment with ceftazidime/avibactam-containing regimens was the only independent predictor of survival. CONCLUSIONS: Ceftazidime/avibactam appears to be an effective treatment against serious infections caused by KPC-Kp.

Epidemiology and diagnosis of pulmonary embolism in lung cancer patients: is there a role for age adjusted D-dimers cutoff?

Our knowledge about the incidence of pulmonary embolism (PE) and the performance of age adjusted D-dimers (Dd) cutoff amongst patients with lung cancer (LC) and suspected PE, remains limited. We retrospectively analyzed all clinically suspected patients who underwent computed tomography pulmonary angiography (CTPA) in a tertiary hospital during a 19 month period. Cancer diagnosis was established using ICD10 code. Eligible for Dd analysis were those tested up to 24 h prior to the scan. We analyzed 2549 patients (54.6% males, median age 68.8 years, IQR 57-78), 15.8% had active LC and 5.4% other cancers (oC), while 70% were scanned in the Emergency Department (ED) and the rest during hospitalization. Overall incidence of PE was 16%. LC, but not oC, increased significantly the risk for PE (OR 1.58, 95% CI 1.21-2.06). LC patients were less likely to have bilateral (aOR 0.16, 95% CI 0.07-0.4) or central PE (aOR 0.2, 95% CI 0.09-0.48). Amongst those diagnosed with PE in the ED, LC increased all-cause inhospital mortality (aOR 6.7, 95% CI 2.64-16.95). When age adjusted instead of conventional Dd cutoff was used for ruling out PE in the ED, specificity for LC patients increased (10.16% vs 3.91%) without false negative tests (negative likelihood ratio-NLR = 0). A higher cutoff of 1.13 mg/l raised specificity to 28.9%, with only one case missed (sensitivity: 97.4%, NLR: 0.09, 95% CI 0.01-0.64). LC increases the risk for PE and adversely affects prognosis. Age adjusted and probably an even higher, "LC adjusted" Dd cutoff, could increase the specificity of the test without compromising its sensitivity.

Management of KPC-producing Klebsiella pneumoniae infections.

BACKGROUND: Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) has become one of the most important contemporary pathogens, especially in endemic areas. AIMS: To provide practical suggestion for physicians dealing with the management of KPC-KP infections in critically ill patients, based on expert opinions. SOURCES: PubMed search for relevant publications related to the management of KPC-KP infections. CONTENTS: A panel of experts developed a list of 12 questions to be addressed. In view of the current lack of high-level evidence, they were asked to provide answers on the bases of their knowledge and experience in the field. The panel identified several key aspects to be addressed when dealing with KPC-KP in critically ill patients (preventing colonization in the patient, preventing infection in the colonized patient and colonization of his or her contacts, reducing mortality in the infected patient by rapidly diagnosing the causative agent and promptly adopting the best therapeutic strategy) and provided related suggestions that were based on the available observational literature and the experience of panel members. IMPLICATIONS: Diagnostic technologies could speed up the diagnosis of KPC-KP infections. Combination treatment should be preferred to monotherapy in cases of severe infections. For non-critically ill patients without severe infections, results from randomized clinical trials are needed for ultimately weighing benefits and costs of using combinations rather than monotherapy. Multifaceted infection control interventions are needed to decrease the rates of colonization and cross-transmission of KPC-KP.

Use of nebulized antimicrobials for the treatment of respiratory infections in invasively mechanically ventilated adults: a position paper from the European Society of Clinical Microbiology and Infectious Diseases.

With an established role in cystic fibrosis and bronchiectasis, nebulized antibiotics are increasingly being used to treat respiratory infections in critically ill invasively mechanically ventilated adult patients. Although there is limited evidence describing their efficacy and safety, in an era when there is a need for new strategies to enhance antibiotic effectiveness because of a shortage of new agents and increases in antibiotic resistance, the potential of nebulization of antibiotics to optimize therapy is considered of high interest, particularly in patients infected with multidrug-resistant pathogens. This Position Paper of the European Society of Clinical Microbiology and Infectious Diseases provides recommendations based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology regarding the use of nebulized antibiotics in invasively mechanically ventilated adults, based on a systematic review and meta-analysis of the existing literature (last search July 2016). Overall, the panel recommends avoiding the use of nebulized antibiotics in clinical practice, due to a weak level of evidence of their efficacy and the high potential for underestimated risks of adverse events (particularly, respiratory complications). Higher-quality evidence is urgently needed to inform clinical practice. Priorities of future research are detailed in the second part of the Position Paper as guidance for researchers in this field. In particular, the panel identified an urgent need for randomized clinical trials of nebulized antibiotic therapy as part of a substitution approach to treatment of pneumonia due to multidrug-resistant pathogens.

Nebulized antibiotics in mechanically ventilated patients: roadmap and challenges.

INTRODUCTION: Nebulized antibiotics use has become common practice in the therapeutics of pneumonia in cystic fibrosis patients. There is an increasing interest in their use for respiratory infections in mechanically ventilated (MV) patients in order to a) overcome pharmacokinetic issues in the lung compartment with traditional systemic antibiotic use and b) prevent the emergence of multi-drug-resistant (MDR) pathogens. Areas covered: The beneficial effects of antibiotic nebulization in MV patients e.g. increasing efficacy, reduced toxicity and prevention of resistance are described. Physicochemical parameters of optimal lung deposition, characteristics of currently available nebulizers, practical aspects of the procedure, including drug preparation and adjustments of ventilator and circuit parameter are presented. Antibiotics used in nebulized route, along with efficacy in various clinical indications and safety issues are reviewed. Expert commentary: The safety of nebulization of antibiotics has been proven in numerous studies; efficacy as adjunctive treatment to intravenous regimens or as monotherapy has been demonstrated in ventilator-associated pneumonia or ventilator-associated tracheobronchitis due to MDR or susceptible pathogens. However, due to the heterogeneity of studies, multiple meta-analyses fail to demonstrate a clear effect. Clarification of indications, standardization of technique and implementation of clinical practice guidelines, based on new large-scale trials will lead to the optimal use of nebulized antibiotics.

Global survey on nebulization of antimicrobial agents in mechanically ventilated patients: a call for international guidelines.

Nebulized antimicrobial agents are increasingly administered for treatment of respiratory infections in mechanically ventilated (MV) patients. A structured online questionnaire assessing the indications, dosages and recent patterns of use for nebulized antimicrobial agents in MV patients was developed. The questionnaire was distributed worldwide and completed by 192 intensive care units. The most common indications for using nebulized antimicrobial agent were ventilator-associated tracheobronchitis (VAT; 58/87), ventilator-associated pneumonia (VAP; 56/87) and management of multidrug-resistant, Gram-negative (67/87) bacilli in the respiratory tract. The most common prescribed nebulized agents were colistin methanesulfonate and sulfate (36/87, 41.3% and 24/87, 27.5%), tobramycin (32/87, 36.7%) and amikacin (23/87, 26.4%). Colistin methanesulfonate, amikacin and tobramycin daily doses for VAP were significantly higher than for VAT (p < 0.05). Combination of parenteral and nebulized antibiotics occurred in 50 (86%) of 58 prescriptions for VAP and 36 (64.2%) of 56 of prescriptions for VAT. The use of nebulized antimicrobial agents in MV patients is common. There is marked heterogeneity in clinical practice, with significantly different in use between patients with VAP and VAT. Randomized controlled clinical trials and international guidance on indications, dosing and antibiotic combinations to improve clinical outcomes are urgently required.

Bloodstream infections in ICU with increased resistance: epidemiology and outcomes.

BACKGROUND: Aim of this study was to evaluate the epidemiology and outcomes of hospital-acquired bloodstream infections (HA-BSI) in Greek intensive care units (ICU). METHODS: Secondary analysis of data from 29 ICU collected during the EUROBACT study, a large prospective, observational, multination survey of HA-BSI. First episodes of HA-BSI acquired in the ICU or within 48 hours prior to admission were recorded. RESULTS: Gram-negative bacteria predominated namely Acinetobacter sp, Klebsiella sp, Pseudomonas sp (73.3% of monomicrobial infections) followed by Gram-positive cocci (18.3%); fungi (7.6%) and anaerobes (0.8%). Overall 73.3% of isolates were multidrug resistant (MDR), 47.1% extensively resistant (XDR) and 1.2% pan-drug resistant (PDR). Carbapenems were the most frequent empirically prescribed antibiotics, while colistin was the most frequently adequate; for both, calculated mean total daily doses were suboptimal. Overall 28-day all-cause mortality was 33.3%. In the multivariate analysis, factors adversely affecting outcome were higher SOFA score at HA-BSI onset (OR 1.19; 95% CI 1.08-1.31, P=0.0006), need for renal supportive therapy (OR 2.75; 95% CI 1.35-5.59, P=0.0053), and for vasopressors/inotropes (OR 2.68; CI 1.18-6.12, P=0.02); adequate empirical treatment had a protective effect (OR 0.48; CI 0.24-0.95, P=0.03). CONCLUSION: TIMELY administration of adequately dosed treatment regimens and early ICU admission of critically ill patients could help in improving outcomes.

Rituximab in critically ill patients.

Rituximab is a monoclonal chimeric antibody used in the treatment of CD20-positive B-cell malignancies and rheumatoid arthritis. However, it is used in several other off-label indications including acute graft-versus-host disease. We sought to critically examine the role of rituximab in the treatment of acute graft versus host disease (aGVHD) in critically ill patients and the potential associations with infectious complications in transplant recipients.

Community acquired methicillin resistant Staphylococcus aureus pneumonia: an update for the emergency and intensive care physician.

Pneumonia caused by community-acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) among individuals without healthcare-associated (HA) risk factors was first recognized a decade ago. CA-MRSA has now been established as a pathogen responsible for rapidly progressive, frequently fatal disease manifesting as necrotizing pneumonia, severe sepsis and necrotizing fasciitis. The frequency of occurrence, risk factors, and optimal treatment of CA-MRSA pneumonia remain unclear and vary significantly across countries. CA-MRSA is resistant to ß-lactam antimicrobials due to the acquisition of novel methicillin resistance genetic cassettes. Additionally many CA-MRSA strains produce Panton-Valentine leukocidin (PVL), due to which they probably exceed the virulence of hospital-acquired MRSA isolates (HA-MRSA). CA-MRSA pneumonia requires early suspicion -especially in young otherwise healthy individuals with rapidly evolving clinical picture presenting with cavitary consolidation, bilateral infiltrates, pleural effusion and hemoptysis. Prompt hospitalization and aggressive treatment with intravenous antibiotics is warranted to improve outcomes. Therapeutic approach for severe CA-MRSA infections and particularly pneumonia is generally the same as that for invasive HA-MRSA infections. New anti-MRSA agents and possible combinations are of great importance to be evaluated in the future.

Prevalence of 16S rRNA methylase genes in Enterobacteriaceae isolates from a Greek university hospital.

16S ribosomal RNA methylase-mediated high-level resistance to 4-,6-aminoglycosides has been reported in clinical isolates of gram-negative bacilli from several countries. Three of 1534 (0.2%) isolates of Klebsiella pneumoniae and three of 734 (0.4%) Proteus mirabilis isolates from a university hospital in Athens, Greece, were positive for rmtB and highly resistant to all aminoglycosides tested (MICs ≥256 mg/L). Two of the K. pneumoniae rmtB-bearing isolates, were KPC-2 and OXA-10 producers and the third was a DHA-1 producer. One of the P. mirabilis isolates was a VIM-1 and OXA-10 producer and one was an OXA-10 producer. All rmtB-harbouring isolates were clonally unrelated. None of the E. coli (n = 1398) and Enterobacter spp. (n = 414) isolates were positive for armA, rmtA, rmtB, rmtC or rmtD.

First influenza season after the 2009 pandemic influenza: characteristics of intensive care unit admissions in adults and children in Vall d'Hebron Hospital.

To assess potential differences in epidemiology and management of patients admitted with influenza infection in the intensive care unit (ICU) during the first post-pandemic influenza period. Observational prospective study comparing September 2009-January 2010 with September 2010-January 2011. Variables captured: demographics, co-morbidities, physiological parameters, outcomes and management. Analysis was performed using SPSS v. 13.0; significance was set at p 0.5. Data from 53 patients, 38 adults (age, median 41.5 years; interquartile range (IQR) 32.8-51.3) and 15 children (age, median 2 years, IQR 0.5-9) are presented. Vaccination rates were 0% and 4.3% during the first and second periods, respectively. Differences postpandemic were: 100% of episodes developed after December compared with 16.7% in the 2009 season. Younger children were affected (median age 0.8 years (IQR 0.3-4.8) vs 7 years (IQR 1.25-11.5), p 0.05) and influenza B caused 8.7% of ICU admissions. Influenza A (H1N1) 2009 and respiratory syncytial virus epidemics occurred simultaneously (42.8% of children) and bacterial co-infections doubled (from 10% to 21.7%); the prevalence of co-infections (viral or bacterial) increased from 10% to 39.1% (OR 5.8, 95% CI 1.3-24.8). Respiratory syndromes without chest X-ray opacities reflecting exacerbation of asthma or chronic obstructive pulmonary disease, bronchitis or bronchiolitis increased (from 6.9% to 39.1%, p<0.05) and pneumonia decreased (from 83.3% to 56.5%, p <0.05). Primary viral pneumonia predominated among ICU admissions. Postpandemic ICU influenza developed later, with some cases of influenza B, more frequent bacterial and viral co-infections and more patients with severe acute respiratory infection with normal chest X-ray. Increasing vaccination rates among risk-group individuals is warranted to prevent ICU admission and death.

Colonization and infection by colistin-resistant Gram-negative bacteria in a cohort of critically ill patients.

In recent years there has been renewed interest in colistin for the treatment of infections by multidrug-resistant Gram-negative bacteria, causing concern that increasing use may be accompanied by the emergence of resistance. This is a retrospective cohort study of colonization and infection by colistin-resistant (CR) gram-negative bacteria in critically ill patients. Colonization data were based on surveillance culture results. Among 150 patients, 78 (52%) were colonized by CR Gram-negative bacteria. Among them, 30 (20%) were colonized by Klebsiella pneumoniae isolates and 51 (34%) were colonized by intrinsically resistant to colistin (CIR) enterobacteriaceae. Seven cases of infection were caused by CR K. pneumoniae and 12 cases by CIR strains. The main risk factor for colonization by CR pathogens was colistin treatment.

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.

Successful virological outcome in an HIV-infected individual with a three-class resistant variant and an insertion in the protease genome with a Tipranavir based regimen.

BACKGROUND: Multi-class HIV-1 resistant variants are not rare nowadays. Genotypic and phenotypic resistance testing (including virtual phenotype) constitutes an important tool for optimizing antiretroviral treatment. AIM: To report a case of discrepancy between resistance interpretation and virological outcome. METHODS: A case of a multi-drug experienced patient is presented. Genotypic and/or virtual phenotypic testing analysis was used. RESULTS: The patient after 10 years of antiretroviral therapy with 11 different regimens unable to produce full virological suppression and with a rapidly declining CD4 count, achieved a successful virological outcome with a scheme containing Tipranavir boosted with low dose of ritonavir. Of note, the patient was screened for Tipranavir 1182.48 study and was found ineligible after genotypic analysis. CONCLUSIONS: Virologic suppression was achieved despite the fact that neither an active agent was included in the backbone regimen nor the resistance profile could ensure the effectiveness of Tipranavir.

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.

Population pharmacokinetic analysis of colistin methanesulfonate and colistin after intravenous administration in critically ill patients with infections caused by gram-negative bacteria.

Colistin is used to treat infections caused by multidrug-resistant gram-negative bacteria (MDR-GNB). It is administered intravenously in the form of colistin methanesulfonate (CMS), which is hydrolyzed in vivo to the active drug. However, pharmacokinetic data are limited. The aim of the present study was to characterize the pharmacokinetics of CMS and colistin in a population of critically ill patients. Patients receiving colistin for the treatment of infections caused by MDR-GNB were enrolled in the study; however, patients receiving a renal replacement therapy were excluded. CMS was administered at a dose of 3 million units (240 mg) every 8 h. Venous blood was collected immediately before and at multiple occasions after the first and the fourth infusions. Plasma CMS and colistin concentrations were determined by a novel liquid chromatography-tandem mass spectrometry method after a rapid precipitation step that avoids the significant degradation of CMS and colistin. Population pharmacokinetic analysis was performed with the NONMEM program. Eighteen patients (6 females; mean age, 63.6 years; mean creatinine clearance, 82.3 ml/min) were included in the study. For CMS, a two-compartment model best described the pharmacokinetics, and the half-lives of the two phases were estimated to be 0.046 h and 2.3 h, respectively. The clearance of CMS was 13.7 liters/h. For colistin, a one-compartment model was sufficient to describe the data, and the estimated half-life was 14.4 h. The predicted maximum concentrations of drug in plasma were 0.60 mg/liter and 2.3 mg/liter for the first dose and at steady state, respectively. Colistin displayed a half-life that was significantly long in relation to the dosing interval. The implications of these findings are that the plasma colistin concentrations are insufficient before steady state and raise the question of whether the administration of a loading dose would benefit critically ill patients.

Nationwide surveillance of Streptococcus pneumoniae in Greece: patterns of resistance and serotype epidemiology.

This nationwide study assessed the antimicrobial susceptibility and seroprevalence of Streptococcus pneumoniae in paediatric carriage isolates and in clinical isolates from adult pneumococcal disease in Greece during the years 2004-2006. Among 780 isolates recovered from the nasopharynx of children <6 years old attending day-care centres, non-susceptibility rates to penicillin, cefuroxime, ceftriaxone, erythromycin, tetracycline and trimethoprim/sulfamethoxazole were 34.7%, 25.1%, 1.0%, 33.5%, 26.4% and 44.2%, respectively. Among 89 adult clinical isolates, the respective rates were 48.3%, 46.1%, 5.6%, 48.3%, 32.6% and 40.4%. High-level resistance to penicillin, cefuroxime and ceftriaxone was recorded for 14.4%, 23.3% and 0.1% of paediatric carriage isolates, whereas for clinical adult isolates the respective rates were 25.8%, 38.2% and 2.2%. No resistance to levofloxacin and moxifloxacin was recorded, although 3.5% of paediatric carriage isolates and 23.2% of adult clinical isolates had minimum inhibitory concentrations of ciprofloxacin >2mg/L. Serotypes 19F, 14, 23F and 6B were the most prevalent among carriage and clinical isolates. The 7-valent pneumococcal conjugate vaccine was estimated to provide coverage against 71.7% of paediatric carriage isolates and 51.3% of adult clinical isolates. Resistance rates among clinical isolates from adult sources were higher than those recorded among paediatric carriage S. pneumoniae isolates and displayed an increasingly resistant profile compared with previous reports from our country, warranting continuous vigilance.

Multifocal spinal and extra-spinal Mycobacterium chelonae osteomyelitis in a renal transplant recipient.

Only localized cases of Mycobacterium chelonae osteomyelitis have been reported. In this article, a 55-year-old immunosuppressed man with M. chelonae osteomyelitis and multiple spinal and extra-spinal involvement is presented. The patient had nodule-pustular skin lesions, spondylodiscitis at multiple levels, and osteolytic lesions at extra-spinal locations. Biopsy and cultures of the osseous lesions showed M. chelonae osteomyelitis. The patient started antimycobacterial chemotherapy with ciprofloxacin and clarithromycin. Progressive cervical kyphosis associated with anterior wedged deformity of the C5 vertebra and posterior C5-C6 spondylolisthesis resulted in compression of the spinal cord and neurological impairment. The patient underwent anterior decompression and C4-C6 arthrodesis using a titanium mesh cage and cervical plate. About 15 months after the initiation of chemotherapy and 5 months after surgery, the patient was pain free, with significant improvement of his neurological function. In the presence of immunosuppression, the physician should be alert for unusual or opportunistic pathogens of osteomyelitis. Long-term antimicrobial chemotherapy and surgical intervention is the cornerstone of successful treatment of multifocal bone M. chelonae infection.

Efficacy and safety of an anti-retroviral combination regimen including either efavirenz or lopinavir-ritonavir with a backbone of two nucleoside reverse transcriptase inhibitors.

The efficacy and safety of a combination regimen including either efavirenz or lopinavir-ritonavir was examined in a cohort of 65 patients positive for human immunodeficiency virus-1 (HIV-1). Both the efavirenz (n = 33, 18 anti-retroviral naive) and lopinavir-ritonavir (n = 32, 15 naive) regimens achieved significant changes from baseline CD4 cell counts and HIV RNA levels after 108 weeks (p < 0.01). Despite diminished immunological and virological parameters at study entry, the lopinavir-ritonavir group showed greater virological effects than the efavirenz group after 108 weeks (median change 3.3 log(10), interquartile range (IQR) 2.2-3.8 log(10) vs. 2.4 log(10), IQR 0.9-3.3 log(10), respectively, p 0.004). Use of lopinavir-ritonavir, in contrast to use of efavirenz, was associated with significant hypertriglyceridaemia.

Prevalence of resistance-associated mutations in newly diagnosed HIV-1 patients in Greece.

The prevalence of HIV-1 drug resistance mutations in naïve patients has been previously shown to differ greatly with the geographic origin. The purpose of this study was to prospectively estimate the prevalence of HIV-1 drug resistance in Greece by analyzing a representative sample of newly HIV-1 diagnosed patients, as part of the SPREAD collaborative study. Protease (PR) and partial reverse transcriptase (RT) sequences were determined from 101 newly diagnosed HIV-1 patients, in Greece, during the period September 2002--August 2003, representing one-third of the total newly diagnosed HIV-1 patients in the same time period. The prevalence of HIV-1 drug resistance was estimated according to the IAS-USA mutation table taking into account all mutations in RT and only major mutations in PR region. The overall prevalence of resistance was 9% [95% confidence interval (CI): 4.2--16.2%]. The prevalence of mutations associated with resistance to NRTIs was 5% (95% CI: 1.6--11.2%), for NNRTIs was 4% (95% CI: 1.1--9.8%), while no major resistance mutations were found in PR. No multi-class resistance was detected in the study population. The prevalence of resistant mutations in the recent seroconverters was 22%. For two individuals, there was clear evidence for transmitted resistance based on epidemiological information for a known source of HIV-1 transmission. The prevalence of the HIV-1 non-B subtypes and recombinants was 52%.