Protection of vaccination versus hybrid immunity against infection with COVID-19 Omicron variants among Health-Care Workers.

BACKGROUND AIM: The Omicron COVID-19 variants BA.1* and BA.2* evade immune system leading to increased transmissibility and breakthrough infections. We aim to test the hypothesis that immunity achieved post COVID-19 infection combined with vaccination (hybrid immunity), is more effective against Omicron infection than vaccination alone in a health-care setting. METHODS: Data on regular pre-emptive PCR testing from all Health-Care Workers (HCWs) at Laiko University Hospital from 29th December 2020, date on which the national COVID-19 immunization program began in Greece, until 24th May 2022, were retrospectively collected and recorded. The infection rate was calculated after December 21st, 2021, when Omicron was the predominant circulating variant in Greece, as the total number of infections (positive PCR COVID-19 test regardless of symptoms) divided by the total person-months at risk. RESULTS: Of 1,305 vaccinated HCWs who were included in the analysis [median age of 47 (IQR: 36, 56) years, 66.7 % women], 13 % and 87 % had received 2 or 3 vaccine doses (full and booster vaccination), respectively. A COVID-19 infection had occurred in 135 of 1,305 of participants prior to Omicron predominance. Of those 135 HCWs with hybrid immunity only 13 (9.6 %) were re-infected. Of the 154 and 1,016 HCWs with full and booster vaccination-induced immunity, respectively, 71 (46.1 %, infection rate 13.4/100 person-months) and 448 (44.1 %, infection rate 12.2/100 person-months) were infected during the follow up period. No association between gender or age and COVID-19 infection was found and none of the participants had a severe infection or died. CONCLUSIONS: Hybrid immunity confers higher protection by almost 5-fold compared to full or booster vaccination for COVID-19 infection with the Omicron variant among HCWs who are at high risk of exposure. This may inform public health policies on how to achieve optimal immunity in terms of the timing and mode of vaccination.

A Simple Prognostic Score for Critical COVID-19 Derived from Patients without Comorbidities Performs Well in Unselected Patients.

We aimed to search for laboratory predictors of critical COVID-19 in consecutive adults admitted in an academic center between 16 September 2020−20 December 2021. Patients were uniformly treated with low-molecular-weight heparin, and dexamethasone plus remdesivir when SpO2 < 94%. Among consecutive unvaccinated patients without underlying medical conditions (n = 241, 49 year-old median, 71% males), 22 (9.1%) developed critical disease and 2 died (0.8%). White-blood-cell counts, neutrophils, neutrophil-to-lymphocyte ratio, CRP, fibrinogen, ferritin, LDH and γ-GT at admission were each univariably associated with critical disease. ROC-defined cutoffs revealed that CRP > 61.8 mg/L, fibrinogen > 616.5 mg/dL and LDH > 380.5 U/L were each associated with critical disease development, independently of age, sex and days from symptom-onset. A score combining higher-than-cutoff CRP (0/2), LDH (0/1) and fibrinogen (0/1) predicted critical disease (AUC: 0.873, 95% CI: 0.820−0.926). This score performed well in an unselected patient cohort (n = 1228, 100% unvaccinated) predominantly infected by the alpha variant (AUC: 0.718, 95% CI: 0.683−0.753), as well as in a mixed cohort (n = 527, 65% unvaccinated) predominantly infected by the delta variant (AUC: 0.708, 95% CI: 0.656−0.760). Therefore, we propose that a combination of standard biomarkers of acute inflammatory response, cell death and hypercoagulability reflects the severity of COVID-19 per se independently of comorbidities, age and sex, being of value for risk stratification in unselected patients.

Alterations in cortisol and interleukin-6 secretion in patients with COVID-19 suggestive of neuroendocrine-immune adaptations.

PURPOSE: The beneficial effect of glucocorticoids in coronavirus disease (COVID-19) is established, but whether adrenal cortisol secretion is impaired in COVID-19 is not fully elucidated. In this case-control study, we investigated the diurnal free bioavailable salivary cortisol secretion in COVID-19 patients. METHODS: Fifty-two consecutive COVID-19 patients-before dexamethasone treatment in cases required-recruited between April 15 to June 15, 2021, (NCT04988269) at Laikon Athens University-Hospital, and 33 healthy age- and sex-matched controls were included. Diurnal salivary cortisol (8 a.m., 12, 6, and 10 p.m.), plasma adrenocorticotropin (ACTH) and aldosterone, and serum interleukin-6 (IL-6) and C-reactive protein (CRP) levels were assessed. Diurnal salivary dehydroepiandrosterone (DHEA) and IL-6 were also assessed in subgroups of patients. RESULTS: Median CRP and IL-6 measurements were about sixfold higher in patients than controls (both p < 0.001) Morning salivary cortisol levels did not differ between the two groups, but patients exhibited higher median levels of evening and nocturnal salivary cortisol compared to controls [0.391 (0.054, 0663) vs. 0.081 (0.054, 0.243) µg/dl, p < 0.001 and 0.183 (0.090, 0.834) vs. 0.054 (0.054, 0.332) µg/dl, p < 0.001, respectively], resulting in higher time-integrated area under the curve (AUC) (4.81 ± 2.46 vs. 2.75 ± 0.810, respectively, p < 0.001). Circulating ACTH, DHEA, and aldosterone levels were similar in patients and controls. Serum IL-6, but not ACTH levels, was strongly correlated with nocturnal cortisol salivary levels (ρ = 0.555, p < 0.001) in patients. CONCLUSIONS: Increased evening and nocturnal but not morning cortisol secretion may occur in even clinically mild COVID-19. In the context of acute viral infection (COVID-19), IL-6 may partially replace ACTH as a stimulus of the glucocorticoid-secreting adrenal zona-fasciculata without influencing the secretion of DHEA and aldosterone. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT04988269?term=yavropoulou&draw=2&rank=3 (NCT04988269).

Vaccination Hesitancy among Health-Care-Workers in Academic Hospitals Is Associated with a 12-Fold Increase in the Risk of COVID-19 Infection: A Nine-Month Greek Cohort Study.

Health-Care-Workers (HCWs) are considered at high risk for SARS-CoV-2 infection. We sought to compare rates and severity of Coronavirus disease 2019 (COVID-19) among vaccinated and unvaccinated HCWs conducting a retrospective cohort study in two tertiary Academic Hospitals, namely Laiko and Attikon, in Athens, Greece. Vaccinated by BNT162b2 Pfizer-BioNTech COVID-19 mRNA vaccine and unvaccinated HCWs were included and data were collected between 1 January 2021 and 15 September 2021. Overall, 2921 of 3219 HCWs without a history of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection were fully vaccinated during the study period (90.7% at each Hospital). Demographic characteristics were comparable between 102/2921 (3.5%) vaccinated and 88/298 (29.5%) unvaccinated HCWs with COVID-19, although age and occupation differed significantly. None were in need of hospital admission in the vaccinated Group, whereas in the unvaccinated Group 4/88 (4.5%) were hospitalized and one (1.1%) died. Multivariable logistic regression analysis revealed that lack of vaccination was an independent risk factor for COVID-19 with an odds ratio 11.54 (95% CI: 10.75-12.40). Vaccination hesitancy among HCWs resulted to highly increased COVID-19 rates; almost one in three unvaccinated HCWs was SARS-CoV-2 infected during the 9-month period. The absolute need of vaccination of HCWs, including boosting dose, is highlighted. Evidence should be used appropriately to overcome any hesitancy.

Outpatient parenteral antimicrobial therapy (OPAT) in the UK: a cross-sectional survey of acute hospital trusts and health boards.

This study reviews the current OPAT service provision in the UK and evaluates concordance with the national OPAT practice guidelines (standards of care). We conducted a survey of acute hospital trusts and health boards in the UK regarding OPAT practices between June and September 2017. 165 (93%) of the 178 acute hospital trusts/health boards that were contacted responded to the survey. 100 (61%) indicated they had an OPAT service. Ten (10%) OPAT services did not involve an infection specialist. Bone and joint infections, and skin and soft-tissue infections were the most common conditions treated. Most OPAT services (74%) hold weekly multidisciplinary meetings/virtual ward rounds to review patient's progress. 73% had a dedicated OPAT database. We identified variations in practice and concordance with the national OPAT good practice guidelines. In an era of increasing demand for home-based care, further studies are required to identify the optimal configuration of OPAT services with regards to quality and patient safety.

Clinical efficacy, cost analysis and patient acceptability of outpatient parenteral antibiotic therapy (OPAT): a decade of Sheffield (UK) OPAT service.

Outpatient parenteral antimicrobial therapy (OPAT) has evolved relatively slowly in the UK. This study describes the OPAT service based in a large UK teaching hospital in Sheffield, and examines the clinical efficacy, patient acceptability and costs saved over a 10-year period. Data on 3812 episodes of OPAT administered between January 2006 and January 2016 were retrieved from a prospectively maintained electronic database. This study compared the real costs of the OPAT service with estimated costs of conventional inpatient care for these patient episodes, and analysed patient feedback questionnaires that were administered randomly between January 2014 and January 2015. A wide range of infections were managed during the 10-year period. Skin and soft tissue infections accounted for 57% of OPAT episodes. The total number of bed-days saved was 49,854. A successful outcome (cure or improvement) was found in 3357 (88%) episodes. Re-admission occurred in 265 (7%) episodes. The rates of healthcare-associated infections were low: 15 intravenous-line-related infections were recorded (0.3 per 1000 OPAT patient-days). Patient acceptance and satisfaction with OPAT were high. OPAT cost 15%, 39%, 40% and 44% of inpatient costs for an infectious diseases unit, national average costs, other departments (non-infectious diseases unit), and the minimum national average costs for each diagnostic category, respectively. This study shows that OPAT is safe, clinically efficacious and acceptable for treating a wide range of infections with high levels of patient satisfaction and substantial cost savings.

The clinical evidence and the role of imiquimod in the extramammary Paget disease.

Extramammary Paget disease is a rare disease. Different treatment options are used for its management, among them treatment with imiquimod. Our aim is to clarify the efficacy and safety of the use of topical imiquimod cream in the treatment of extramammary Paget disease. In this article the current literature in Pubmed and Scopus on this topic is reviewed. According to the literature the topical use of imiquimod can be used as first-line treatment in different dosages and durations with excellent results, reaching a 87.5% cure rate with rare complications. The available evidence is currently limited to case reports and a single case series, but is definitely in favor of imiquimod use as an alternative treatment for extramammary Paget disease.

Ultrasensitive amplification refractory mutation system real-time PCR (ARMS RT-PCR) assay for detection of minority hepatitis B virus-resistant strains in the era of personalized medicine.

Resistance to antiviral treatment for chronic hepatitis B virus (HBV) has been associated with mutations in the HBV polymerase region. This study aimed at developing an ultrasensitive method for quantifying viral populations with all major HBV resistance-associated mutations, combining the amplification refractory mutation system real-time PCR (ARMS RT-PCR) with a molecular beacon using a LightCycler. The discriminatory ability of this method, the ARMS RT-PCR with molecular beacon assay, was 0.01 to 0.25% for the different HBV resistance-associated mutations, as determined by laboratory-synthesized wild-type (WT) and mutant (Mut) target sequences. The assay showed 100% sensitivity for the detection of mutant variants A181V, T184A, and N236T in samples from 41 chronically HBV-infected patients under antiviral therapy who had developed resistance-associated mutations detected by direct PCR Sanger sequencing. The ratio of mutant to wild-type viral populations (the Mut/WT ratio) was >1% in 38 (63.3%) of 60 samples from chronically HBV-infected nucleos(t)ide analogue-naive patients; combinations of mutations were also detected in half of these samples. The ARMS RT-PCR with molecular beacon assay achieved high sensitivity and discriminatory ability compared to the gold standard of direct PCR Sanger sequencing in identifying resistant viral populations in chronically HBV-infected patients receiving antiviral therapy. Apart from the dominant clones, other quasispecies were also quantified. In samples from chronically HBV-infected nucleos(t)ide analogue-naive patients, the assay proved to be a useful tool in detecting minor variant populations before the initiation of the treatment. These observations need further evaluation with prospective studies before they can be implemented in daily practice.

Amphiaraos of Attica: the "Second Asclepius".

Amphiaraos is one of the most prominent Greek heroes. He was the son of god Apollo and student of Centaur Chiron from whom he learned the art of medicine. He was thought to be the "Second Asclepius" and he had many sanctuaries around Greece of which the most well known is the Amphiaraeion of Oropos, near Athens. The aim of this study is to present the genealogical tree and life of Amphiaraos, as well as the methods used in his sanctuaries in order to offer cure in the ill pilgrims.

Guillain-Barre syndrome presenting with sensory disturbance following a herpes virus infection: a case report.

INTRODUCTION: We present a case of an unusual clinical manifestation of Guillain-Barre syndrome following a pre-existing herpes virus infection. Although there have been several reports describing the co-existence of herpes virus infection and Guillain-Barre syndrome, we undertook a more in-depth study of the cross-reactivity between herpes viruses and recommend a follow-up study based on serology tests. CASE PRESENTATION: A 39-year-old healthy Caucasian man with Guillain-Barre syndrome presented to our facility initially with sensory disturbance, followed by an atypical descending pattern of clinical progression. On physical examination, our patient showed hot and cold temperature sensory disturbance under the T4 vertebrae level, symmetrically diminished muscle power mainly to his lower limbs, blurred vision, a loss of taste and paresis and diminished reflexes of his lower limbs. Serology test results for common viruses on hospital admission were positive for cytomegalovirus immunoglobulin M, cytomegalovirus immunoglobulin G, herpes simplex virus immunoglobulin M, herpes simplex virus immunoglobulin G, Epstein-Barr virus immunoglobulin M, and varicella zoster virus immunoglobulin G, borderline for Epstein-Barr virus immunoglobulin G and negative for varicella zoster virus immunoglobulin M. At one month after hospital admission his test results were positive for cytomegalovirus immunoglobulin M, cytomegalovirus immunoglobulin G, herpes simplex virus immunoglobulin G, Epstein-Barr virus immunoglobulin G, varicella zoster virus immunoglobulin G, borderline for herpes simplex virus immunoglobulin M and negative for Epstein-Barr virus immunoglobulin M and varicella zoster virus immunoglobulin M. At his six month follow-up, tests were positive for cytomegalovirus immunoglobulin G, herpes simplex virus immunoglobulin M, herpes simplex virus immunoglobulin G, Epstein-Barr virus immunoglobulin G and varicella zoster virus immunoglobulin G and negative for cytomegalovirus immunoglobulin M, Epstein-Barr virus immunoglobulin M and varicella zoster virus immunoglobulin M. CONCLUSIONS: The clinical manifestation of Guillain-Barre syndrome in our patient followed a combined herpes virus infection. The cross-reactivity between these human herpes viruses may have a pathogenic as well as evolutionary significance. Our patient showed seroconversion at an early stage of Epstein-Barr virus immunoglobulin M to immunoglobulin G antibodies, suggesting that Epstein-Barr virus might have been the cause of this syndrome. Even if this case is not the first of its kind to be reported, it may contribute to a better understanding of the disease and the cross-reaction mechanisms of herpes virus infections. This case report may have a broader clinical impact across more than one area of medicine, suggesting that cooperation between different specialties is always in the patient's best interest.

Aseptic meningitis with urinary retention: a case report.

Introduction. Aseptic meningitis is serious inflammation of the meninges caused by agents including viruses, non-viral pathogens, non-infectious conditions and chemicals. Case Presentation. This study concerns the case of a 16-year-old healthy Greek female with persistent fever, mild headache and acute urinary retention, secondary to aseptic meningitis. Physical examination revealed no distinct signs of meningeal irritation. The urinary bladder was palpable, painless and over-distended. Serology carried out for common viruses was as follows: CMV IgG (-), CMV IgM (-), HSV IgG (-), HSV IgM (+), VZ IgG (+), VZ IgM (-), EBV IgG (-) and EBV IgM (+). During recovery in hospital, three trials of removing a urinary catheter were carried out; during the first two attempts the patient was unable to urinate and had a loss of bladder sensation. On the third attempt the patient had modest bladder perception but she left a post-voiding residual, and was instructed to perform bladder self-catheterization. Seven days after being discharged the patient underwent a full recovery. Conclusion. There are few reports concerning aseptic meningitis together with acute urinary retention. A number of these cases concern so-called "meningitis-retention syndrome," which implies an underlying CNS mechanism, while others concerned an underlying peripheral nervous system mechanism.

ß-D-glucan assay for the diagnosis of invasive fungal infections: a meta-analysis.

We aimed to assess the accuracy of measuring serum or plasma (1→3)-ß-D-glucan (BDG) for the diagnosis of invasive fungal infections (IFIs) by means of a meta-analysis of relevant studies. We searched in bibliographic databases for relevant cohort or case-control studies. We primarily compared BDG between patients with proven or probable IFIs (excluding Pneumocystis jirovecii infections), according to the criteria of the European Organization for Research and Treatment of Cancer/Mycoses Study Group or similar criteria, and patients without IFIs (excluding healthy individuals as controls). A total of 2979 patients (594 with proven or probable IFIs), included in 16 studies, were analyzed. The pooled sensitivity of BDG was 76.8% (95% confidence interval [CI], 67.1%-84.3%), and the specificity was 85.3% (95% CI, 79.6%-89.7%). The area under the summary receiver operating characteristic curve was 0.89. Marked statistical heterogeneity was noted. BDG has good diagnostic accuracy for distinguishing proven or probable IFIs from no IFIs. It can be useful in clinical practice, if implemented in the proper setting and interpreted after consideration of its limitations.

Do PubMed and Google searches help medical students and young doctors reach the correct diagnosis? A pilot study.

BACKGROUND: In the era of the World Wide Web we sought to examine whether the use of PubMed and Google can help physicians to improve their diagnostic skills. METHODS: Twenty-six diagnostic cases presented in the case records of the New England Journal of Medicine during 2005 were used for our analysis. Three investigators (one trainee doctor and two final year medical students), tried determining the diagnosis, initially without and afterwards with the use of PubMed and Google. RESULTS: A slight increase in the proportion of correct diagnoses obtained was seen following the employment of the formerly mentioned Internet resources, specifically 15.4%, 2.9%, and 11.5% increase for the 3 investigators respectively (from 17 correct diagnoses out of the 26 cases to 21 correct diagnoses out of 26 for investigator A, from 11/26 to 12/26 for investigator B, and from 11/26 to 13/26 for investigator C). This increase was not statistically significant. One investigator was helped more by Google, one by PubMed, and one was equally assisted by the two resources. CONCLUSIONS: We believe that these preliminary findings justify the induction of further studies in order to clarify whether resources such as PubMed and Google may substantially aid physicians and medical students in the differential diagnosis process.

Fournier's gangrene in a patient after third-degree burns: a case report.

INTRODUCTION: Fournier's gangrene is characterized by tissue ischemia leading to rapidly progressing necrotizing fasciitis. CASE PRESENTATION: We present the case of a patient with Fournier's gangrene after third-degree burns. Clinical manifestations, laboratory results and treatment options are discussed. CONCLUSION: Fournier's gangrene is a surgical emergency. Although it can be lethal, it is still a challenging situation in the field of surgical infections.

Candida albicans versus non-albicans bloodstream infection in patients in a tertiary hospital: an analysis of microbiological data.

Considerable changes in the relative frequency of systemic infections due to various Candida species as well as their in vitro susceptibility patterns have been noted in several parts of the world. We performed an analysis of microbiological data of patients with candidaemia at the University general (tertiary) hospital of Heraklion, Greece. During the study period (March 2001 to July 2006) 140 patients had candidaemia. Among them, 64/140 (46%) had candidaemia due to C. albicans and 76/140 (54%) due to non-albicans species (19/76, 25%, C. glabrata; 30/76, 40%, C. tropicalis; 20/76, 26%, C. parapsilosis; 2/76, 3%, C. lusitaniae; 3/76, 4%, C. krusei; and 2/76, 3%, C. guilliermondii). 75 isolates were tested for in vitro susceptibility to antifungal agents with E-test. No isolate was found to be resistant to amphotericin. From 34 C. albicans isolates, 5 (15%) were not susceptible to itraconazole, and 1 (3%) to fluconazole. The C. guilliermondii and the C. lusitaniae isolates were not susceptible to itraconazole. All 11 C. glabrata isolates were not susceptible to ketoconazole and itraconazole, with only 5 (45%) to fluconazole. In line with results of other relevant studies, we documented that a considerable proportion of Candida bloodstream infections were due to non-albicans Candida species.

Candida albicans versus non-albicans intensive care unit-acquired bloodstream infections: differences in risk factors and outcome.

OBJECTIVE: In this study we sought to identify differences in risk factors and outcome of critically ill patients with Candida albicans and non-albicans candidemia. METHODS: Nonimmunosuppressed, nonneutropenic patients with candidemia diagnosed after intensive care unit (ICU) admission were included in a prospective observational study in a medical-surgical ICU at a tertiary academic hospital in Athens, Greece. RESULTS: During the study period (January 2001 to December 2005), 56 candidemia episodes in 1037 ICU admissions were included (5.4%). Of these patients, 36/56 (64.3%) had candidemia due to C. albicans and 20/56 (35.7%) due to non-albicans species (8/56 [14.3%] C. glabrata, 6/56 [10.7%] C. tropicalis, 3/56 [5.4%] C. parapsilosis, 1/56 [1.8%] C. lusitaniae, 1/56 [1.8%] C. krusei and 1/56 [1.8%] C. dubliniensis). Administration of glucocorticosteroids, central venous catheter placement, and preexisting candiduria were independently associated with candidemia due to C. non-albicans species (Odds ratio [OR]: 45.1, 95% confidence interval [CI]: 3.0-669.9; OR: 26.2, 95% CI: 2.1-334.8; and OR: 16.5, 95% CI: 1.6-173.9, respectively). The treatment response rate differed significantly between patients with C. albicans and patients with C. non-albicans bloodstream infections (29/36 [80.6%] vs 9/20 [45%], P = 0.006). Overall mortality was higher in patients with non-albicans species than C. albicans bloodstream infections (18/20 [90%] vs 19/36 [52.8%], P = 0.005). Multivariable logistic regression analysis revealed that candidemia due to non-albicans species was independently associated with death (OR: 6.7, 95% CI: 1.2-37.7). CONCLUSIONS: In the subset of critically ill nonimmunosuppressed patients, candidemia caused by non-albicans species occurred more frequently in those with medical devices or receiving steroids. Candidemia due to non-albicans species was also associated with higher mortality.

Linezolid: effectiveness and safety for approved and off-label indications.

Multi-drug resistant Gram-positive cocci have emerged as significant pathogens of community- and hospital-acquired infections. Several antimicrobial agents that can be used for the treatment of these infections are presently available. However, the most appropriate treatment for each infection has not been established. Linezolid seems to be a promising choice. Linezolid is bactericidal against Streptococci and bacteriostatic against Enterococci and Staphylococci. It has excellent pharmacokinetic and pharmacodynamic profiles, which allow early change from intravenous to oral administration. In addition, its effectiveness for the treatment of Gram-positive infections in immunocompetent and immunodeficient patients have been studied in several randomized controlled trials. In this review, the authors summarize all the available evidence regarding the effectiveness and safety of linezolid compared with other antimicrobial agents for its approved and off-label indications.

Daptomycin for endocarditis and/or bacteraemia: a systematic review of the experimental and clinical evidence.

BACKGROUND: Endocarditis and bacteraemia are devastating infections with high mortality. Gram-positive cocci are the most commonly isolated pathogens. In an era of multidrug-resistant pathogens, the evaluation of new treatment options is important. Daptomycin is a cyclic lipopeptide that is active against most of these pathogens. Furthermore, it is a bactericidal antibiotic, a factor that is frequently considered in the choice of treatment of patients with bacteraemia and endocarditis. METHODS: We performed a systematic review of the evidence for the effectiveness of daptomycin in the treatment of patients and animals with endocarditis and/or bacteraemia. We searched PubMed and Scopus databases for relevant studies. Case reports, case series, controlled trials, randomized controlled trials and comparative studies using experimental animal models were included. RESULTS: The most reliable information comes from the single multicentre randomized controlled trial conducted on this issue, which showed that daptomycin is a promising antibiotic for the treatment of patients with Staphylococcus aureus bacteraemia and endocarditis. The experimental models indicate that the combination of daptomycin with rifampicin or gentamicin can improve outcomes further. Finally, in several of the published relevant case reports daptomycin was administered in patients with haematological malignancies. CONCLUSIONS: Daptomycin is a promising antibiotic that has been already approved for the treatment of patients with right-sided endocarditis and bacteraemia. However, the available clinical evidence is limited and further evaluation of the antibiotic is warranted. The commonly reported de novo development of resistance is a major concern that may limit its use. More controlled trials are needed, especially for patients infected with multidrug-resistant Gram-positive cocci, comparing daptomycin with other available treatment options, including glycopeptides and oxazolidinones.

Daptomycin for treatment of patients with bone and joint infections: a systematic review of the clinical evidence.

The treatment of bone and joint infections, mainly caused by Gram-positive pathogens, can be difficult and quite challenging since it frequently involves prolonged administration of antibiotics as well as appropriate surgical procedures. First-line drugs have failed in some cases to cure the underlying infection. We performed a systematic review of the available evidence to clarify further the effectiveness and safety of daptomycin in the treatment of bone and joint infections. Cure of infection was achieved in 43/53 cases (81.1%). The results of the reviewed articles are promising with regard to the effectiveness and safety profile of this new antibiotic for bone and joint infections that are not responsive to other traditionally used antimicrobial agents. Although these reports are encouraging, the relatively frequent emergence of antimicrobial resistance associated with prolonged administration of daptomycin should be considered seriously.

Linezolid for the treatment of patients with central nervous system infection.

OBJECTIVE: To review the available evidence regarding the use of linezolid for the treatment of patients with central nervous system (CNS) infections. DATA SOURCES: Relevant studies were identified through searches of the PubMed, Current Contents, and Cochrane databases (publications archived until October 2006). STUDY SELECTION AND DATA EXTRACTION: Case reports, case series, prospective and retrospective studies, and randomized controlled trials were eligible for inclusion in our review if they evaluated the effectiveness and safety of linezolid for the treatment of patients with CNS infections. DATA SYNTHESIS: In 18 (42.9%) of the 42 relevant cases identified, patients had undergone neurosurgical operations and/or had prosthetic devices. Meningitis was the most common CNS infection, accounting for 20 (47.6%) cases. Other CNS infections included brain abscesses (14; 33.3%), ventriculitis (5; 11.9%), and ventriculo-peritoneal shunt infection (3; 7.1%). In the 39 patients in whom the responsible pathogen was isolated, those predominantly responsible for the CNS infections were: penicillin-nonsusceptible Streptococcus pneumoniae (7; 17.9%), vancomycin-resistant enterococci (6; 15.4%), Nocardia spp. (5; 12.8%), methicillin-resistant Staphylococcus epidermidis (4; 10.3%), and methicillin-resistant Staphylococcus aureus (3; 7.7%). Of the 42 patients who received linezolid for the treatment of CNS infections, 38 (90.5%) were either cured or showed clinical improvement of the infection. The mean duration of follow-up was 7.2 months; no recurrent CNS infection was reported. CONCLUSIONS: The limited published data suggest that linezolid may be considered for the treatment of patients with CNS infections in cases of failure of previously administered treatment or limited available options.