Association of a polymorphism in the indoleamine- 2,3-dioxygenase gene and interferon-α-induced depression in patients with chronic hepatitis C.

Interferon (IFN)-α treatment for infectious diseases and cancer is associated with significant depressive symptoms that can limit therapeutic efficacy. Multiple mechanisms have been implicated in IFN-α-induced depression including immune, neuroendocrine and neurotransmitter pathways. To further explore mechanisms of IFN-α-induced depression and establish associated genetic risk factors, single nucleotide polymorphisms in genes encoding proteins previously implicated in IFN-α-induced depression were explored in two self-reported ethnic groups, Caucasians (n=800) and African Americans (n=232), participating in a clinical trial on the impact of three pegylated IFN-α treatment regimens on sustained viral response in patients with chronic hepatitis C. Before treatment, all subjects were free of psychotropic medications and had a score ≤20 on the Center for Epidemiologic Studies Depression Scale (CES-D), which was used to assess depressive symptom severity throughout the study. In Caucasians, a polymorphism (rs9657182) in the promoter region of the gene encoding indoleamine-2,3-dioxygenase (IDO1) was found to be associated with moderate or severe IFN-α-induced depressive symptoms (CES-D>20) at 12 weeks of IFN-α treatment (P=0.0012, P<0.05 corrected). Similar results were obtained for treatment weeks 24, 36 and 48. In subjects homozygous for the risk allele (CC, n=150), the odds ratio for developing moderate or severe depressive symptoms at treatment week 12 was 2.91 (confidence interval: 1.48-5.73) compared with TT homozygotes (n=270). rs9657182 did not predict depression in African Americans, who exhibited a markedly lower frequency of the risk allele at this locus. The findings in Caucasians further support the notion that IDO has an important role in cytokine-induced behavioral changes.

Population pharmacokinetics of peginterferon alfa-2b in pediatric patients with chronic hepatitis C.

PURPOSE: The aim of this study was to characterize the population pharmacokinetics of peginterferon (PEG-IFN) alfa-2b in pediatric patients with chronic hepatitis C and to identify covariates influencing PEG-IFN alfa-2b disposition. METHODS: Pharmacokinetic data from a multicenter open-label study of subcutaneously administered peginterferon alfa-2b (60 µg/m(2)/wk) plus oral ribavirin (15 mg/kg/day) in patients with chronic hepatitis C aged 3-17 years old was used to develop a population pharmacokinetic nonlinear mixed-effects model. RESULTS: The final population pharmacokinetic analysis was conducted with the pooled data from 107 pediatric patients. A one-compartment model with first-order absorption, first-order elimination, exponential inter-individual variability on clearance, and a combination additive and proportional residual error model adequately described the PEG-IFN alfa-2b pharmacokinetic profile. Age (apparent clearance and apparent volume of distribution) and sex (apparent clearance) were significant covariates. The mean body surface area normalized apparent clearance of PEG-IFN alfa-2b was 0.56 L/h/m(2), and was similar when evaluated across the pediatric age groups. CONCLUSION: The final population model suggests age-dependent increases in clearance and volume of distribution of PEG-IFN alfa-2b in pediatric patients with chronic hepatitis C. The apparent clearance normalized to body surface area was similar across pediatric age groups, supporting the use of body size-adjusted dosing in pediatric subjects.

Durability of sustained response shown in paediatric patients with chronic hepatitis C who were treated with interferon alfa-2b plus ribavirin.

Long-term studies in adults indicate that sustained virologic response (SVR) after combination treatment for chronic hepatitis C (CHC) predicts long-term clearance. Although peginterferon plus ribavirin is now standard care for children with CHC, long-term follow-up studies are not yet available. This study evaluated durability of virologic response over 5 years in children previously treated with interferon alfa-2b plus ribavirin (IFN/R). Ninety-seven of 147 children with CHC, who were treated with IFN/R and completed the 6-month follow-up in two previous clinical trials, participated in this long-term follow-up study. All were assessed annually for up to 5 years; patients with SVR were assessed for durability of virologic response. Children with SVR (n = 56) and those with detectable hepatitis C virus (HCV) RNA 24-week post-treatment (n = 41) were followed for a median of 284 weeks. Overall, 70% (68/97) of patients completed the 5-year follow-up. One patient with genotype 1a CHC had SVR and relapsed at year 1 of follow-up with the same genotype. Kaplan-Meier estimate for sustained response at 5 years was 98% (95% CI: 95%, 100%). Six patients with low-positive HCV RNA levels (n = 4) or missing HCV RNA at the 24-week follow-up visit (n = 2) in the initial treatment studies had virologic response during this long-term follow-up study. Linear growth rate was impaired during treatment with rapid increases in the immediate 6 months post-treatment. Mean height percentile at the end of the 5-year follow-up was slightly less than the mean pretreatment height percentile. Five patients experienced serious adverse events; none related to study drug exposure. SVR after IFN/R predicts long-term clearance of HCV in paediatric patients; growth normalized in the majority of children during the long-term follow-up. Similar long-term results could be expected after peginterferon alfa-2b plus ribavirin treatment.

Interleukin 28B polymorphisms are the only common genetic variants associated with low-density lipoprotein cholesterol (LDL-C) in genotype-1 chronic hepatitis C and determine the association between LDL-C and treatment response.

Low-density lipoprotein cholesterol (LDL-C) levels and interleukin 28B (IL28B) polymorphism are associated with sustained viral response (SVR) to peginterferon/ribavirin (pegIFN/RBV) for chronic hepatitis C (CHC) infection. IL28B has been linked with LDL-C levels using a candidate gene approach, but it is not known whether other genetic variants are associated with LDL-C, nor how these factors definitively affect SVR. We assessed genetic predictors of serum lipid and triglyceride levels in 1604 patients with genotype 1 (G1) chronic hepatitis C virus (HCV) infection by genome-wide association study and developed multivariable predictive models of SVR. IL28B polymorphisms were the only common genetic variants associated with pretreatment LDL-C level in Caucasians (rs12980275, P = 4.7 × 10(-17), poor response IL28B variants associated with lower LDL-C). The association was dependent on HCV infection, IL28B genotype was no longer associated with LDL-C in SVR patients after treatment, while the association remained significant in non-SVR patients (P < 0.001). LDL-C was significantly associated with SVR for heterozygous IL28B genotype patients (P < 0.001) but not for homozygous genotypes. SVR modelling suggested that IL28B heterozygotes with LDL-C > 130 mg/dL and HCV RNA ≤600 000 IU/mL may anticipate cure rates >80%, while the absence of these two criteria was associated with an SVR rate of <35%. IL28B polymorphisms are the only common genetic variants associated with pretreatment LDL-C in G1-HCV. LDL-C remains significantly associated with SVR for heterozygous IL28B genotype patients, where LDL-C and HCV RNA burden may identify those patients with high or low likelihood of cure with pegIFN/RBV therapy.

Hepatitis C treatment among racial and ethnic groups in the IDEAL trial.

Previous studies of chronic hepatitis C virus (HCV) treatment have demonstrated variations in response among racial and ethnic groups including poorer efficacy rates among African American and Hispanic patients. The individualized dosing efficacy vs flat dosing to assess optimaL pegylated interferon therapy (IDEAL) trial enrolled 3070 patients from 118 United States centres to compare treatment with peginterferon (PEG-IFN) alfa-2a and ribavirin (RBV) and two doses of PEG-IFN alfa-2b and RBV. This analysis examines treatment response among the major racial and ethnic groups in the trial. Overall, sustained virologic response (SVR) rates were 44% for white, 22% for African American, 38% for Hispanic and 59% for Asian American patients. For patients with undetectable HCV RNA at treatment week 4, the positive predictive value of SVR was 86% for white, 92% for African American, 83% for Hispanic and 89% for Asian American patients. The positive predictive values of SVR in those with undetectable HCV RNA at treatment week 12 ranged from 72% to 81%. Multivariate regression analysis using baseline characteristics demonstrated that treatment regimen was not a predictor of SVR. Despite wide-ranging SVR rates among the different racial and ethnic groups, white and Hispanic patients had similar SVR rates. In all groups, treatment response was largely determined by antiviral activity in the first 12 weeks of treatment. Therefore, decisions regarding HCV treatment should consider the predictive value of the early on-treatment response, not just baseline characteristics, such as race and ethnicity.

Iclaprim reduces the incidence and severity of Staphylococcus aureus-induced septic arthritis in a murine model.

Staphylococcus aureus is the most common non-gonococcal aetiology of septic arthritis. The efficacy of iclaprim against S. aureus LS-1, a clinical strain identified from a patient with septic arthritis, was studied in MF1 mice to evaluate the activity of iclaprim, which is in clinical development, in preventing joint infections. Iclaprim (2.5-80 mg kg- 1) administered as a single dose via the tail vein reduced the incidence of S. aureus septic arthritis and mortality in an experimental murine model of septic arthritis.

Foot infections in diabetes (DFIs) in the out-patient setting: an Italian multicentre observational survey.

AIMS: To conduct a multicentre observational study to describe management of foot infections in diabetes in the out-patient setting in Italy. PATIENTS AND METHODS: Ten centres equally distributed nationwide were asked to collect, by means of a spreadsheet (Access/Excel Microsoft program), data concerning 30 consecutive diabetic patients with foot infections deemed suitable for antibiotic treatment in the out-patient setting. Centres with > or = 5 years' experience of out-patient management were selected. Data from 271 consecutive patients treated as out-patients were collected and analysed by the central coordinator. Statistical analysis was performed using the SPSS statistical software package. RESULTS: Lesions were mainly located at the toes and midfoot (33.6 and 30.2%, respectively); 63 (23.2%) patients had multiple ulcers. Seventy (25.8%) patients also had concomitant osteomyelitis. Three hundred and four pathogens, including Gram-positive and Gram-negative aerobes and anaerobes, were isolated in 219/271 patients (80.8%) by culturing debrided tissue (71.2%) or purulent material (28.8%). Infections were polymicrobial in 33.8% of patients. The most common pathogens were Staphylococcus aureus (27.3%) and Pseudomonas spp. (20.4%); enterobacteriaceae, enterococci, streptococci and anaerobes accounted for 11.5, 7.6, 6.9 and 1.9%, respectively. Antibiotics were frequently administered by parenteral route and frequently in combination. Piperacillin/tazobactam was the parenteral antibiotic most frequently utilized (21.1%). Cure/improvement was observed in 93.4% of patients. CONCLUSIONS: Foot ulcers in diabetes are common and serious; the aetiology is often polymicrobial, often including S. aureus and Pseudomonas spp. Treatment in the out-patient setting is safe and effective, and penicillins together with beta-lactamase inhibitors and fluoroquinolones are the most frequent choice.

[Catheter-associated urinary tract infections: epidemiology and prevention]. / Le infezioni urinarie associate a catetere: epidemiologia e prevenzione.

Urinary tract infections (UTIs) represent the second most often observed infectious diseases in community, following the respiratory tract infections. In the United States, these infections account for up to 7 million/year of visits, with a mean yearly expense for the related antibiotic treatment that has been estimated in more than one billion dollars. In nosocomial setting, UTIs represent the most frequent diseases, whose incidence equates 40% of nosocomial infections overall considered; about 80% of UTIs is related to urinary catheterization. In the present review, the authors, after a brief introduction about epidemiology, pathogenesis and aetiology of urinary tract infections, consider two particular settings: long term care facilities, where UTIs represent the most often diagnosed and treated infections, and the Intensive Care Units where occurrence of urinary tract infections represents an especially frequent event as well. Patients referred to both these settings are particular, as they undergo, in most cases, to urinary catheterization. After describing the pathogenesis of UTIs related to catheterization, either short- or long term, the authors consider the different currently available catheters, focusing on silver-coated and silver alloy coated (silver, gold, and platinum). With regard to this latter issue, results presented by a number of papers in the literature are reported, where clinical experiences following the use of these urinary catheters are described. In their conclusion, authors suggest the opportunity to increase any prevention strategy able to reduce the incidence of infections related to urinary catheterization and its consequences, as a more rational length and modality of catheterization, in addition to the use of innovative catheters.

Outpatient parenteral antibiotic therapy for bone and joint infections: an italian multicenter study.

In the early eighties, the advantages of outpatient parenteral antibiotic therapy (OPAT) (reduced costs, no hospitalization trauma in children, no immobilization syndrome in elderly, reduction in nosocomial infections by multiresistant organisms) were identified in the United States, and suitable therapeutic programs were established. Currently, more than 250,000 patients per year are treated according to an OPAT program. In order to understand the different ways of managing OPAT and its results, a National OPAT Registry was set up in 2003 in Italy. Analysis of data concerning osteomyelitis, septic arthritis, prosthetic joint infection and spondylodiskitis, allowed information to be acquired about 239 cases of bone and joint infections, with particular concern to demographics, therapeutic management, clinical response, and possible side effects. Combination therapy was the first-line choice in 66.9% of cases and frequently intravenous antibiotics were combined with oral ones. Teicoplanin (38%) and ceftriaxone (14.7%), whose pharmacokinetic/pharmacodynamic properties permit once-a-day administration, were the two top antibiotics chosen; fluoroquinolones (ciprofloxacin and levofloxacin) were the most frequently utilized oral drugs. Clinical success, as well as patients' and doctors' satisfaction with the OPAT regimen was high. Side-effects were mild and occurred in 11% of cases. These data confirm that the management of bone and joint infections in an outpatient setting is suitable, effective and safe.

A pilot study on prevention of catheter-related urinary tract infections with fluoroquinolones.

The objective of this multicenter, randomized, controlled, parallel group trial was to evaluate the efficacy of levofloxacin 250 mg oral, once daily (LVFX), placebo one tablet oral once daily (Placebo [P] group) and ciprofloxacin (CPFX) 500 mg oral, twice daily (single blind), prophylaxis in preventing bacteriuria (> or = 10(3) CFU/ml) in post-surgical catheterized patients. In the modified intention-to-treat (M-ITT) population of the 82 enrolled patients, negative bacteriuria was observed in 92% of LVFX group, in 80% of P group and in 100% of CPFX group while in the per-protocol (PP) population figures were: 100%, 86.4% and 100% respectively. Only one symptomatic urinary tract infection and one surgical wound infection were observed in the P group. Both drugs were well tolerated, showing a safety profile comparable to placebo. The high frequency of negative bacteriuria in the placebo group sounds encouraging as it underlines that the adoption of closed urinary drainage system catheters in hospital setting may reduce the frequency of hospital-acquired infections.

Clinical efficacy and tolerability of levofloxacin in patients with liver disease: a prospective, non comparative, observational study.

The aim of this open, non comparative, observational study was to assess the clinical and bacteriological efficacy, the tolerability and safety of levofloxacin for treatment of concurrent bacterial infections in patients with chronic liver disease. Overall, 40 patients (inpatients or outpatients) were recruited to the study (28 with UTI, 6 with pneumonia, and 6 with spontaneous bacterial peritonitis (SBP)). Patients affected by UTI received 250 mg oral levofloxacin once daily for five days; patients with pneumonia or SBP underwent a 10/14-day therapeutic oral regimen with 500 mg b.i.d. Clinical evaluation and possible side effects were monitored daily both in out- and in-patients. For all patients, laboratory tests were performed at baseline and 3-4 days after the end of therapy in order to evaluate levofloxacin tolerability. Statistical analysis was performed by means of Student's t test to show differences between cases; all values are reported as means and standard deviations and p values were considered as significant when p<0.05. After treatment, clinical cure and bacteriological eradication were achieved in all patients (40/40; 100%). Adverse events, mainly gastrointestinal disturbances (e.g. nausea), were observed in 5 out of 40 patients (12.5%) and no neurotoxic effects were registered (e.g. anxiety, hallucinations, convulsions, mental confusion). No significant variation in laboratory tests due to hematic crasis and/or hepatic and renal disorders was observed. Levofloxacin proved to be highly efficacious and safe in the treatment of bacterial infections in patients affected by liver disease.

[Treatment of acute bacterial tonsillopharyngitis in pediatrics: a meta-analysis]. / Trattamento della faringotonsillite acuta batterica in età pediatrica: una metanalisi.

Pharyngo-tonsillitis represents the most common infection of the upper respiratory tract, its treatment being the most common cause for prescribing antibiotics. Efficacy, safety and compliance of cefaclor were compared with those of other antibiotics in the treatment of paediatric acute bacterial tonsillo-pharyngitis in a meta-analysis of randomized controlled trials published between 1979 and 2003. Overall, evaluations were performed on 16 studies (Medline/PubMed, keywords "Cefaclor and tonsillo-pharyngitis) which proved eligible (Jadad score > or = 1); twelve out of 16 studies were multicentre ones, only one was a double-blind study. Mostly, the comparator agent was a beta-lactam, in four cases it was a macrolide. Efficacy and safety were end-points of all studies whereas only 13 and 4 studies evaluated adverse events and compliance, respectively. The analysis was based on a 2 x 2 contingency table with classification by treatment and number of improvements/cures, side-effects, and compliance of the individual studies. The global estimate of the effective treatment was obtained with the weighted mean of the log OR (Odds Ratio) according to Mantel-Haenszel and associated confidence intervals (CI) at 95%. Chi-square test was performed. All the calculations were performed using SAS v.8. Clinical efficacy evaluation, number of improvements/cures, did not evidence a statistically significant difference among cefaclor and comparators (93.8% vs 92.3%; Odds Ratio 1.21, IC 0.95/1.48). In the cefaclor-treated patients, adverse events were observed in a statistically significant lower percentage compared to other antibiotics: 8.5% vs 15.5% (Odds Ratio 0.49, IC 0.22/0.76; P < 0.0001). Compliance was observed in a similar proportion in both the two groups, cefaclor and comparators (Cefaclor, mean 100%; comparators, mean 98.3%). The present meta-analysis proves that in the treatment of paediatric acute bacterial tonsillo-pharyngitis cefaclor exhibits a clinical efficacy equal to other antibiotics usually employed in this setting, similar compliance but superior safety.

Transient bacteraemia due to Chryseobacterium indologenes in an immunocompetent patient: a case report and literature review.

A 51-year-old woman was admitted to the emergency unit with diffuse headache, visus reduction, and paraesthesias of the trigeminal area and the left hand. Three days after admission she showed shaking chills, vomiting, and sudden onset of fever (39·4°C). Blood cultures were performed soon after fever onset. Fever persisted for the whole day, decreasing slowly after 12 hours. No empirical antibiotic treatment was started in order to better define the diagnosis. Fever completely disappeared the day after. Two blood cultures for aerobes were positive for Chryseobacterium indologenes. The patient was discharged with the diagnosis of transient bacteraemia and transferred to the neurology unit for further investigations. C. indologenes infections are described in 31 studies with a total of 171 cases (pneumonia and bacteraemia being the most frequent). Our case is the first report of transient bacteraemia caused by C. indologenes in an immunocompetent, non-elderly patient without needing medical devices.

Clinical comparison of cefaclor twice daily versus amoxicillin-clavulanate or erythromycin three times daily in the treatment of patients with streptococcal pharyngitis.

The present study was undertaken to compare the efficacy and safety of a new regimen of cefaclor (25 mg/kg BID) with amoxicillin-clavulanate and erythromycin TID at standard doses for the treatment of pediatric patients with acute pharyngotonsillitis (APT). A total of 673 children (age range, 2 to 12 years) with signs and symptoms of APT were enrolled; 245 of these children who had a positive throat culture for group A beta-hemolytic streptococci (GABHS) entered the study and were randomly assigned to receive cefaclor 25 mg/kg BID, amoxicillin-clavulanate 15 mg/kg TID, or erythromycin 15 mg/kg TID. A 10-day antibiotic course was prescribed for each patient. Clinical and bacteriologic responses were assessed at the end of treatment (day 10) and at the follow-up visit (day 30). All GABHS strains isolated from throat cultures were tested for in vitro sensitivity to the antibiotics used in the study. Side effects (mainly nausea) were rare and mild in each group and did not require discontinuation of therapy. No GABHS strain was resistant to cefaclor or to amoxicillin-clavulanate; 37.9% of the strains were resistant to erythromycin. The results indicated that cefaclor given BID seems to be as effective as amoxicillin-clavulanate given TID (cure rate, 91.9% and 90.5%, respectively) and more effective than erythromycin given TID (cure rate, 76.8%) for the treatment of patients with APT. Erythromycin resistance among GABHS is an emerging problem in many geographic areas.

Management of upper respiratory tract infections in primary care in Italy: a national survey.

This prospective study, carried out in Italy during the winter of 1998 by the means of questionnaires, was designed to investigate the diagnostic and therapeutic approach of the Italian general practitioners (GPs) to the management of acute upper respiratory tract infections (URTIs) in adult outpatients. A total of 354 GPs were questioned about ten adult patients each who had visited the surgery with an URTI requiring an antibiotic prescription. Our data showed there was a tendency to prescribe antibiotics only on the basis of clinical diagnosis, microbiological investigations being required very rarely. Orally administered antibiotics were preferred and compliance with the number of daily doses strongly influenced the antibiotic prescription. In patients affected by more severe infections, injectable antibiotics were frequently prescribed.

Short-course therapy with cefaclor for treatment of streptococcal pharyngotonsillitis.

Short-course treatments for streptococcal pharyngotonsillitis with oral cephalosporins or macrolides have resulted in a similar bacteriological and clinical cure rate and better compliance compared with the conventional 10-day course. One hundred and thirty eight of 420 recruited patients had a positive culture for Streptococcus pyogenes and were randomly assigned to receive cefaclor (25 mg/kg/bid) for a 5-day (70 patients) or 10-day (68 patients) course. Patients were assessed clinically and bacteriologically 2-3 days after completing the course and followed up after 20-30 days. All 420 recruited patients belonged to a population of 2800 children who had been previously screened for a streptococcal carrier state to exclude carriers from final evaluation. Clinical cure and bacterial eradication was recorded in 92.8 and 92.6% of patients in groups A and B, respectively. Therefore, short-course therapy with cefaclor may offer an effective alternative treatment to conventional regimens, with potential for better compliance.

Outpatient parenteral antibiotic therapy (OPAT) in different countries: a comparison.

In order to assess how outpatient parenteral antibiotic therapy (OPAT) is managed in different countries, we analyzed the data collected in the USA, UK and Italy by the International OPAT Registry using an ad hoc Access/Excel Microsoft program. The analysis of data concerned 9826 patients in the USA, 981 in the UK and 620 in Italy. Differences were observed in several aspects of OPAT management such as the infections treated and the antibiotics utilized. The duration of therapy also differed: it was much longer in Italy (56.0 average days), than in the USA (22.5 days) and UK (19.9 days). Delivery model, delivery route and infusion devices show substantial differences. The present analysis shows that OPAT is carried out with substantial differences in different countries probably according to different programmes and guidelines adopted.

Topical ciprofloxacin vs intramuscular gentamicin for chronic otitis media.

Clinical and bacteriological efficacy of topical ciprofloxacin hydrochloride was compared with that of intramuscular gentamicin sulfate in two groups composed of 30 patients each, all of whom were affected by chronic otitis media in the acute stage. Antibiotics were randomly given for 5 to 10 days according to the following schedules: ciprofloxacin hydrochloride, four drops (250 mg/mL in saline solution) administered locally twice a day, or gentamicin sulfate, 80 mg administered intramuscularly twice a day. We admitted to the study only adult patients affected by chronic otitis media in the acute stage with perforation of the tympanic membrane, without cholesteatoma, whose bacteriological culture was positive for Pseudomonas susceptible in vitro to ciprofloxacin and gentamicin. The clinical and bacteriological response was stated 12 hours after the interruption of the treatment, and 2 and 3 weeks later (follow-up). A favorable clinical result was observed in 26 (87%) of 30 patients under ciprofloxacin treatment; in 30 patients receiving gentamicin, a favorable clinical response was observed in 20 (66%) and bacteriological eradication in 13 (43%). No relapse at the follow-up was observed. Topical ciprofloxacin seems to be more effective than intramuscular gentamicin in curing Pseudomonas-caused chronic otitis media in the acute stage.

In-vitro sensitivity of amoxicillin/clavulanic acid (Augmentin) to isolated beta-lactamases and in-vitro antibacterial activity.

The in vitro sensitivity of amoxicillin alone and combined with clavulanic acid (ratio 4:1) as been studied by a spectrophotometric method utilizing crude extract of the following enzymes: TEM1, TEM2, SHV1, SHV2, TLE1, HMS1, LXA, P99, ENT208. The in-vitro antibacterial activity of ampicillin, amoxicillin alone and associated with clavulanic acid was also determined by an agar dilution method. Clavulanate protects amoxicillin from the hydrolytic activity of plasmid mediated beta-lactamase, conferring a stability on the beta-lactam comparable with that of cefotaxime. The protection of amoxicillin by means of clavulanic acid reduces the minimal concentration of antibiotic necessary to inhibit most bacterial species and allows bacteria to remain sensitive to the drug which might otherwise be resistant.

What is the role of glycopeptides in intensive care?

Bacterial infections are the major cause of illness and death in the intensive care unit (ICU). In general, each unit is in itself a high risk environment for infections, simultaneously containing many diverse factors that favor the spread of clinically evident and generally serious infections: the constant presence of serious concomitant diseases, the frequent use of invasive diagnostic methods and procedures, the elevated selective pressure caused by multiple and prolonged antibiotic treatment on endogenous and environmental microbial flora. Notwithstanding the fact that the bacterial epidemiology of the ICU varies slightly in different countries and in different ICUs, in the last 15 years a general and progressive increase in the etiology of Gram-positive aerobic bacteria has been observed. Currently, Staphylococcus aureus is the etiologic agent most frequently responsible for infections in the ICU; S. aureus + coagulase-negative Staphylococcus (CoNS) + Enterococcus are responsible for more than 60% of infections. More recent data confirm that next to modifications in bacterial etiology in the ICU, the most alarming phenomenon is the methicillin-resistance of S. aureus (MRSA). The high percentage of multi-resistance compels us to reconsider therapy relative to the choice of antibiotics to use and, in particular, raises the question of possibly selecting the class of glycopeptides, alone or in combination, as the choice of treatment every time that an infection is caused by a Gram-positive microorganism. The use of glycopeptides, as with all antibiotics, must be evaluated in a suitable manner with the objective of limiting the selective pressure on resistant bacterial flora caused by their use. It is widely understood that inappropriate use of antibiotics, such as selecting an antibacterial agent with an inadequate spectrum that is thus ineffective, determines an increase in the mortality rate compared to using an agent with an appropriate spectrum of activity.