Effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections: observational study, systematic reviews and mathematical modelling

BACKGROUND Partner notification is essential to the comprehensive case management of sexually transmitted infections. Systematic reviews and mathematical modelling can be used to synthesise information about the effects of new interventions to enhance the outcomes of partner notification. OBJECTIVE To study the effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections (STIs). DESIGN Secondary data analysis of clinical audit data; systematic reviews of randomised controlled trials (MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials) published from 1 January 1966 to 31 August 2012 and of studies of health-related quality of life (HRQL) [MEDLINE, EMBASE, ISI Web of Knowledge, NHS Economic Evaluation Database (NHS EED), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA)] published from 1 January 1980 to 31 December 2011; static models of clinical effectiveness and cost-effectiveness; and dynamic modelling studies to improve parameter estimation and examine effectiveness. SETTING General population and genitourinary medicine clinic attenders. PARTICIPANTS Heterosexual women and men. INTERVENTIONS Traditional partner notification by patient or provider referral, and new partner notification by expedited partner therapy (EPT) or its UK equivalent, accelerated partner therapy (APT). MAIN OUTCOME MEASURES Population prevalence; index case reinfection; and partners treated per index case. RESULTS Enhanced partner therapy reduced reinfection in index cases with curable STIs more than simple patient referral [risk ratio (RR) 0.71; 95% confidence interval (CI) 0.56 to 0.89]. There are no randomised trials of APT. The median number of partners treated for chlamydia per index case in UK clinics was 0.60. The number of partners needed to treat to interrupt transmission of chlamydia was lower for casual than for regular partners. In dynamic model simulations, > 10% of partners are chlamydia positive with look-back periods of up to 18 months. In the presence of a chlamydia screening programme that reduces population prevalence, treatment of current partners achieves most of the additional reduction in prevalence attributable to partner notification. Dynamic model simulations show that cotesting and treatment for chlamydia and gonorrhoea reduce the prevalence of both STIs. APT has a limited additional effect on prevalence but reduces the rate of index case reinfection. Published quality-adjusted life-year (QALY) weights were of insufficient quality to be used in a cost-effectiveness study of partner notification in this project. Using an intermediate outcome of cost per infection diagnosed, doubling the efficacy of partner notification from 0.4 to 0.8 partners treated per index case was more cost-effective than increasing chlamydia screening coverage. CONCLUSIONS There is evidence to support the improved clinical effectiveness of EPT in reducing index case reinfection. In a general heterosexual population, partner notification identifies new infected cases but the impact on chlamydia prevalence is limited. Partner notification to notify casual partners might have a greater impact than for regular partners in genitourinary clinic populations. Recommendations for future research are (1) to conduct randomised controlled trials using biological outcomes of the effectiveness of APT and of methods to increase testing for human immunodeficiency virus (HIV) and STIs after APT; (2) collection of HRQL data should be a priority to determine QALYs associated with the sequelae of curable STIs; and (3) standardised parameter sets for curable STIs should be developed for mathematical models of STI transmission that are used for policy-making. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Cost-effectiveness of point-of-care viral load monitoring of antiretroviral therapy in resource-limited settings: mathematical modelling study

BACKGROUND Monitoring of HIV viral load in patients on combination antiretroviral therapy (ART) is not generally available in resource-limited settings. We examined the cost-effectiveness of qualitative point-of-care viral load tests (POC-VL) in sub-Saharan Africa. DESIGN Mathematical model based on longitudinal data from the Gugulethu and Khayelitsha township ART programmes in Cape Town, South Africa. METHODS Cohorts of patients on ART monitored by POC-VL, CD4 cell count or clinically were simulated. Scenario A considered the more accurate detection of treatment failure with POC-VL only, and scenario B also considered the effect on HIV transmission. Scenario C further assumed that the risk of virologic failure is halved with POC-VL due to improved adherence. We estimated the change in costs per quality-adjusted life-year gained (incremental cost-effectiveness ratios, ICERs) of POC-VL compared with CD4 and clinical monitoring. RESULTS POC-VL tests with detection limits less than 1000 copies/ml increased costs due to unnecessary switches to second-line ART, without improving survival. Assuming POC-VL unit costs between US$5 and US$20 and detection limits between 1000 and 10,000 copies/ml, the ICER of POC-VL was US$4010-US$9230 compared with clinical and US$5960-US$25540 compared with CD4 cell count monitoring. In Scenario B, the corresponding ICERs were US$2450-US$5830 and US$2230-US$10380. In Scenario C, the ICER ranged between US$960 and US$2500 compared with clinical monitoring and between cost-saving and US$2460 compared with CD4 monitoring. CONCLUSION The cost-effectiveness of POC-VL for monitoring ART is improved by a higher detection limit, by taking the reduction in new HIV infections into account and assuming that failure of first-line ART is reduced due to targeted adherence counselling.

Strategies for partner notification for sexually transmitted infections, including HIV

BACKGROUND Partner notification (PN) is the process whereby sexual partners of an index patient are informed of their exposure to a sexually transmitted infection (STI) and the need to obtain treatment. For the person (index patient) with a curable STI, PN aims to eradicate infection and prevent re-infection. For sexual partners, PN aims to identify and treat undiagnosed STIs. At the level of sexual networks and populations, the aim of PN is to interrupt chains of STI transmission. For people with viral STI, PN aims to identify undiagnosed infections, which can facilitate access for their sexual partners to treatment and help prevent transmission. OBJECTIVES To assess the effects of different PN strategies in people with STI, including human immunodeficiency virus (HIV) infection. SEARCH METHODS We searched electronic databases (the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE) without language restrictions. We scanned reference lists of potential studies and previous reviews and contacted experts in the field. We searched three trial registries. We conducted the most recent search on 31 August 2012. SELECTION CRITERIA Published or unpublished randomised controlled trials (RCTs) or quasi-RCTs comparing two or more PN strategies. Four main PN strategies were included: patient referral, expedited partner therapy, provider referral and contract referral. Patient referral means that the patient notifies their sexual partners, either with (enhanced patient referral) or without (simple patient referral) additional verbal or written support. In expedited partner therapy, the patient delivers medication or a prescription for medication to their partner(s) without the need for a medical examination of the partner. In provider referral, health service personnel notify the partners. In contract referral, the index patient is encouraged to notify partner, with the understanding that the partners will be contacted if they do not visit the health service by a certain date. DATA COLLECTION AND ANALYSIS We analysed data according to paired partner referral strategies. We organised the comparisons first according to four main PN strategies (1. enhanced patient referral, 2. expedited partner therapy, 3. contract referral, 4. provider referral). We compared each main strategy with simple patient referral and then with each other, if trials were available. For continuous outcome measures, we calculated the mean difference (MD) with 95% confidence intervals (CI). For dichotomous variables, we calculated the risk ratio (RR) with 95% CI. We performed meta-analyses where appropriate. We performed a sensitivity analysis for the primary outcome re-infection rate of the index patient by excluding studies with attrition of greater than 20%. Two review authors independently assessed the risk of bias and extracted data. We contacted study authors for additional information. MAIN RESULTS We included 26 trials (17,578 participants, 9015 women and 8563 men). Five trials were conducted in developing countries. Only two trials were conducted among HIV-positive patients. There was potential for selection bias, owing to the methods of allocation used and of performance bias, owing to the lack of blinding in most included studies. Seven trials had attrition of greater than 20%, increasing the risk of bias.The review found moderate-quality evidence that expedited partner therapy is better than simple patient referral for preventing re-infection of index patients when combining trials of STIs that caused urethritis or cervicitis (6 trials; RR 0.71, 95% CI 0.56 to 0.89, I(2) = 39%). When studies with attrition greater than 20% were excluded, the effect of expedited partner therapy was attenuated (2 trials; RR 0.8, 95% CI 0.62 to 1.04, I(2) = 0%). In trials restricted to index patients with chlamydia, the effect was attenuated (2 trials; RR 0.90, 95% CI 0.60 to 1.35, I(2) = 22%). Expedited partner therapy also increased the number of partners treated per index patient (three trials) when compared with simple patient referral in people with chlamydia or gonorrhoea (MD 0.43, 95% CI 0.28 to 0.58) or trichomonas (MD 0.51, 95% CI 0.35 to 0.67), and people with any STI syndrome (MD 0.5, 95% CI 0.34 to 0.67). Expedited partner therapy was not superior to enhanced patient referral in preventing re-infection (3 trials; RR 0.96, 95% CI 0.60 to 1.53, I(2) = 33%, low-quality evidence). Home sampling kits for partners (four trials) did not result in lower rates of re-infection in the index case (measured in one trial), or higher numbers of partners elicited (three trials), notified (two trials) or treated (one trial) when compared with simple patient referral. There was no consistent evidence for the relative effects of provider, contract or other patient referral methods. In one trial among men with non-gonococcal urethritis, more partners were treated with provider referral than with simple patient referral (MD 0.5, 95% CI 0.37 to 0.63). In one study among people with syphilis, contract referral elicited treatment of more partners than provider referral (MD 2.2, 95% CI 1.95 to 2.45), but the number of partners receiving treatment was the same in both groups. Where measured, there was no statistical evidence of differences in the incidence of adverse effects between PN strategies. AUTHORS' CONCLUSIONS The evidence assessed in this review does not identify a single optimal strategy for PN for any particular STI. When combining trials of STI causing urethritis or cervicitis, expedited partner therapy was more successful than simple patient referral for preventing re-infection of the index patient but was not superior to enhanced patient referral. Expedited partner therapy interventions should include all components that were part of the trial intervention package. There was insufficient evidence to determine the most effective components of an enhanced patient referral strategy. There are too few trials to allow consistent conclusions about the relative effects of provider, contract or other patient referral methods for different STIs. More high-quality RCTs of PN strategies for HIV and syphilis, using biological outcomes, are needed.

Daptomycin versus vancomycin for osteoarticular infections due to methicillin-resistant Staphylococcus aureus (MRSA): a nested case-control study

Vancomycin is the standard antibiotic for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. While daptomycin is approved for MRSA bacteremia, its effectiveness in osteoarticular infections (OAIs) has not been established. A 1:2 nested case-control study of adult patients with MRSA OAIs admitted to an academic center from 2005 to 2010 was carried out. Clinical outcomes and drug toxicity in patients treated with daptomycin versus vancomycin were compared. Twenty patients with MRSA OAIs treated with daptomycin were matched to 40 patients treated with vancomycin. The median age of the patients was 52 years (range, 25-90), and 40 (67 %) were male. Most patients had osteomyelitis (82 %), predominantly from a contiguous source (87 %). Forty percent were diabetics. Diabetic patients were more likely to receive vancomycin than daptomycin [20 (50 %) vs. 4 (20 %); p = 0.03]. Vancomycin was more often combined with antibiotics other than daptomycin [22 (55 %) vs. 5 (25 %); p = 0.03]. The median total antibiotic treatment duration was 48 (daptomycin) vs. 46 days (vancomycin) (p = 0.5). Ninety percent of daptomycin-treated patients had previously received vancomycin for a median of 14.5 days (range, 2-36). Clinical success rates were similar between daptomycin and vancomycin at 3 months [15 (75 %) vs. 27 (68 %); p = 0.8] and 6 months [14 (70 %) vs. 23 (58 %); p = 0.5], even after propensity score-based adjustment for antibiotic assignment. The frequency of adverse events was similar between treatment groups [1 (5 %) vs. 7 (18 %); p = 0.2]. Daptomycin and vancomycin achieved similar rates of clinical success and drug tolerability. Daptomycin is a reasonable alternative for treating MRSA OAIs, particularly in patients where therapy with vancomycin has not been well tolerated.

A Prospective Multicenter SPOG 2003 FN Study of Microbiologically Defined Infections in Pediatric Cancer Patients with Fever and Neutropenia.

BACKGROUND Fever and neutropenia (FN) often complicate anticancer treatment and can be caused by potentially fatal infections. Knowledge of pathogen distribution is paramount for optimal patient management. METHODS Microbiologically defined infections (MDI) in pediatric cancer patients presenting with FN by nonmyeloablative chemotherapy enrolled in a prospective multi-center study were analyzed. Effectiveness of empiric antibiotic therapy in FN episodes with bacteremia was assessed taking into consideration recently published treatment guidelines for pediatric patients with FN. RESULTS MDI were identified in a minority (22%) of pediatric cancer patients with FN. In patients with, compared to without MDI, fever (median, 5 [IQR 3-8] vs. 2 [IQR1-3] days, p < 0.001) and hospitalization (10 [6-14] vs. 5 [3-8] days, p < 0.001) lasted longer, transfer to the intensive care unit was more likely (13 of 95 [14%] vs. 7 of 346 [2.0%], p < 0.001), and antibiotics were given longer (10 [7-14] vs. 5 [4-7], p < 0.001). Empiric antibiotic therapy in FN episodes with bacteremia was highly effective if not only intrinsic and reported antimicrobial susceptibilities were considered but the purposeful omission of coverage for coagulase negative staphylococci and enterococci was also taken into account (81% [95%CI 68 - 90] vs. 96.6% [95%CI 87 - 99.4], p = 0.004) CONCLUSIONS: MDI were identified in a minority of FN episodes but they significantly affected management and the clinical course of pediatric cancer patients. Compliance with published guidelines was associated with effectiveness of empiric antibiotic therapy in FN episodes with bacteremia.

Emergence of methicillin-resistant Staphylococcus pseudintermedius in Switzerland: three cases of urinary tract infections in cats

Methicillin resistance has emerged in clinical isolates of Staphylococcus pseudintermedius from cats in Switzerland. Three cats suffering from urinary tract infections were infected with methicillin-resistant S. pseudintermedius (MRSP). Phenotypic and genotypic characterization of the resistance profile showed that the isolates displayed resistance to all beta-lactams and cephalosporins (blaZ, mecA), fluoroquinolones, tetracyclines [tet(K)], macrolides, lincosamides and streprogramins B [erm(B)], chloramphenicol (catpC221), trimethoprim [dfr(G)] and the aminoglycosides gentamicin [aac(6')-Ie-aph(2')-Ia], kanamycin and neomycin [aph(3')-III] and streptomycin [ant(6)-Ia]. They also harbor the leukocidin gene lukS-I. MRSP represents a new challenge for antibiotic therapy and this zoonotic bacteria may rapidly spread to animals and humans.

Matrix metalloproteinase inhibition lowers mortality and brain injury in experimental pneumococcal meningitis

Pneumococcal meningitis (PM) results in high mortality rates and long-lasting neurological deficits. Hippocampal apoptosis and cortical necrosis are histopathological correlates of neurofunctional sequelae in rodent models and are frequently observed in autopsy studies of patients who die of PM. In experimental PM, inhibition of matrix metalloproteinases (MMPs) and/or tumor necrosis factor (TNF)-converting enzyme (TACE) has been shown to reduce brain injury and the associated impairment of neurocognitive function. However, none of the compounds evaluated in these studies entered clinical development. Here, we evaluated two second-generation MMP and TACE inhibitors with higher selectivity and improved oral availability. Ro 32-3555 (Trocade, cipemastat) preferentially inhibits collagenases (MMP-1, -8, and -13) and gelatinase B (MMP-9), while Ro 32-7315 is an efficient inhibitor of TACE. PM was induced in infant rats by the intracisternal injection of live Streptococcus pneumoniae. Ro 32-3555 and Ro 32-7315 were injected intraperitoneally, starting at 3 h postinfection. Antibiotic (ceftriaxone) therapy was initiated at 18 h postinfection, and clinical parameters (weight, clinical score, mortality rate) were recorded. Myeloperoxidase activities, concentrations of cytokines and chemokines, concentrations of MMP-2 and MMP-9, and collagen concentrations were measured in the cerebrospinal fluid. Animals were sacrificed at 42 h postinfection, and their brains were assessed by histomorphometry for hippocampal apoptosis and cortical necrosis. Both compounds, while exhibiting disparate MMP and TACE inhibitory profiles, decreased hippocampal apoptosis and cortical injury. Ro 32-3555 reduced mortality rates and cerebrospinal fluid TNF, interleukin-1β (IL-1β) and collagen levels, while Ro 32-7315 reduced weight loss and cerebrospinal fluid TNF and IL-6 levels.

Cerebrospinal-fluid cytokine and chemokine profile in patients with pneumococcal and meningococcal meningitis

BACKGROUND Bacterial meningitis is characterized by an intense inflammatory reaction contributing to neuronal damage. The aim of this study was to obtain a comparative analysis of cytokines and chemokines in patients with pneumococcal (PM) and meningococcal meningitis (MM) considering that a clear difference between the immune response induced by these pathogens remains unclear. METHODS The cyto/chemokines, IL-1beta, IL-2, IL-6, TNF-alpha, IFN-gamma, IL-10, IL-1Ra, CXCL8/IL-8, CCL2/MCP-1, CLL3/MIP-1alpha, CCL4/MIP-1gamma and G-CSF, were measured in cerebrospinal fluid (CSF) samples from patients with PM and MM. Additionally, a literature review about the expression of cytokines in CSF samples of patients with MB was made. RESULTS Concerning cytokines levels, only IFN-gamma was significantly higher in patients with Streptococcus pneumoniae compared to those with Neisseria meningitidis, regardless of the time when the lumbar puncture (LP) was made. Furthermore, when samples were compared considering the timing of the LP, higher levels of TNF-alpha (P <0.05) were observed in MM patients whose LP was made within 48 h from the initial symptoms of disease. We also observed that the index of release of cyto/chemokines per cell was significantly higher in PM. From the literature review, it was observed that TNF-alpha, IL-1beta and IL-6 are the best studied cytokines, while reports describing the concentration of the cytokine IL-2, IL-1Ra, G-CSF and CCL4/MIP-1beta in CSF samples of patients with bacterial meningitis were not found. CONCLUSION The data obtained in this study and the previously published data show a similar profile of cytokine expression during PM and MM. Nevertheless, the high levels of IFN-gamma and the ability to release high levels of cytokines with a low number of cells are important factors to be considered in the pathogenesis of PM and thereby should be further investigated. Moreover, differences in the early response induced by the pathogens were observed. However, the differences observed are not sufficient to trigger changes in the current therapy of corticosteroids adopted in both the PM and MM.

In pneumococcal meningitis a novel water-soluble inhibitor of matrix metalloproteinases and TNF-alpha converting enzyme attenuates seizures and injury of the cerebral cortex

Matrix metalloproteinases (MMPs) and TNF-alpha converting enzyme (TACE) contribute to the pathophysiology of bacterial meningitis. To date, MMP-inhibitors studied in models of meningitis were compromised by their hydrophobic nature. We investigated the pharmacokinetics and the effect of TNF484, a water-soluble hydroxamate-based inhibitor of MMP and TACE, on disease parameters and brain damage in a neonatal rat model of pneumococcal meningitis. At 1 mg/kg q6h TNF484 reduced soluble TNF-alpha and the collagen degradation product hydroxyproline in the cerebrospinal fluid. Clinically, TNF484 attenuated the incidence of seizures and was neuroprotective in the cortex. Water-soluble MMP-inhibitors may hold promise in the therapy of bacterial meningitis.

Dexamethasone aggravates hippocampal apoptosis and learning deficiency in pneumococcal meningitis in infant rats.

In an infant rat model of pneumococcal meningitis the effect of dexamethasone on neuronal injury in the hippocampus and on learning disability after recovery from the disease was examined. Treatment with dexamethasone or vehicle was started 18 h after infection, concomitant with antibiotics. Neuronal apoptosis in the hippocampal dentate gyrus 34 h after infection was significantly aggravated by dexamethasone treatment compared with vehicle controls (p = 0.02). Three weeks after acute pneumococcal meningitis, learning capacity of animals was assessed in the Morris water maze. The results showed a significantly impaired learning performance of infected animals treated with dexamethasone compared with vehicle controls (p = 0.01). Dexamethasone had no effect on hippocampal injury or learning in uninfected controls. Thus, dexamethasone as adjuvant therapy increased hippocampal cell injury and reduced learning capacity in this model of pneumococcal meningitis in infant rats.

Outpatient Parenteral Antimicrobial Therapy Practices among Adult Infectious Disease Physicians

Objective. To identify current outpatient parenteral antibiotic therapy practice patterns and complications. Methods. We administered an 11-question survey to adult infectious disease physicians participating in the Emerging Infections Network (EIN), a Centers for Disease Control and Prevention-sponsored sentinel event surveillance network in North America. The survey was distributed electronically or via facsimile in November and December 2012. Respondent demographic characteristics were obtained from EIN enrollment data. Results. Overall, 555 (44.6%) of EIN members responded to the survey, with 450 (81%) indicating that they treated 1 or more patients with outpatient parenteral antimicrobial therapy (OPAT) during an average month. Infectious diseases consultation was reported to be required for a patient to be discharged with OPAT by 99 respondents (22%). Inpatient (282 [63%] of 449) and outpatient (232 [52%] of 449) infectious diseases physicians were frequently identified as being responsible for monitoring laboratory results. Only 26% (118 of 448) had dedicated OPAT teams at their clinical site. Few infectious diseases physicians have systems to track errors, adverse events, or "near misses" associated with OPAT (97 [22%] of 449). OPAT-associated complications were perceived to be rare. Among respondents, 80% reported line occlusion or clotting as the most common complication (occurring in 6% of patients or more), followed by nephrotoxicity and rash (each reported by 61%). Weekly laboratory monitoring of patients who received vancomycin was reported by 77% of respondents (343 of 445), whereas 19% of respondents (84 of 445) reported twice weekly laboratory monitoring for these patients. Conclusions. Although use of OPAT is common, there is significant variation in practice patterns. More uniform OPAT practices may enhance patient safety.

Systemic therapy for atopic dermatitis.

Systemic therapy for atopic dermatitis (AD) is indicated in patients with severe disease refractory to adequate topical treatment. Currently available drugs aim to decrease inflammation by suppressing and/or modulating immune responses and thus may indirectly improve skin barrier function, resulting in a decrease in clinical signs and symptoms in particular pruritus. Before considering systemic treatment, patient adherence to topical treatment including skin care has to be ensured. The selection of the drug depends on the disease severity, localization, complications, concomitant diseases, and age of the patient, but also on their availability and costs as well as the doctor's experience. Bearing in mind the potential risk of resistance, systemic therapy with antibiotics should be exclusively considered in clinically manifest infections such as in children. Here, we review recently published clinical trials and case reports on systemic therapy of pediatric and adult patients with AD to draw conclusions for clinical practice. Although AD is a common disease, controlled clinical studies investigating the efficacy of systemic drugs are scarce, except for cyclosporine, which has been approved for the therapy of severe AD.

Engineered liposomes sequester bacterial exotoxins and protect from severe invasive infections in mice

Gram-positive bacterial pathogens that secrete cytotoxic pore-forming toxins, such as Staphylococcus aureus and Streptococcus pneumoniae, cause a substantial burden of disease. Inspired by the principles that govern natural toxin-host interactions, we have engineered artificial liposomes that are tailored to effectively compete with host cells for toxin binding. Liposome-bound toxins are unable to lyse mammalian cells in vitro. We use these artificial liposomes as decoy targets to sequester bacterial toxins that are produced during active infection in vivo. Administration of artificial liposomes within 10 h after infection rescues mice from septicemia caused by S. aureus and S. pneumoniae, whereas untreated mice die within 24-33 h. Furthermore, liposomes protect mice against invasive pneumococcal pneumonia. Composed exclusively of naturally occurring lipids, tailored liposomes are not bactericidal and could be used therapeutically either alone or in conjunction with antibiotics to combat bacterial infections and to minimize toxin-induced tissue damage that occurs during bacterial clearance

Nosocomial infections in dialysis access.

Nosocomial infections in patients requiring renal replacement therapy have a high impact on morbidity and mortality. The most dangerous complication is bloodstream infection (BSI) associated with the vascular access, with a low BSI risk in arteriovenous fistulas or grafts and a comparatively high risk in central venous catheters. The single most important measure for preventing BSI is therefore the reduction of catheter use by means of early fistula formation. As this is not always feasible, prevention should focus on educational efforts, hand hygiene, surveillance of dialysis-associated events, and specific measures at and after the insertion of catheters. Core measures at the time of insertion include choosing the optimal site of insertion, the use of maximum sterile barrier precautions, adequate skin antisepsis, and the choice of catheter type; after insertion, access care needs to ensure hub disinfection and regular dressing changes. The application of antimicrobial locks is reserved for special situations. Evidence suggests that bundling a selection of the aforementioned measures can significantly reduce infection rates. The diagnosis of central line-associated BSI (CLABSI) is based on clinical signs and microbiological findings in blood cultures ideally drawn both peripherally and from the catheter. The prompt installation of empiric antibiotic treatment covering the most commonly encountered organisms is key regarding CLABSI treatment. Catheter removal is recommended in complicated cases or if cultures yield Staphylococcus aureus, enterococci, Pseudomonas or fungi. In other cases, guide wire exchange or catheter salvage strategies with antibiotic lock solutions may be acceptable alternatives.

Risk of infections during interferon-based treatment in patients with chronic HCV infection and advanced hepatic fibrosis.

BACKGROUND & AIMS Pegylated interferon-based treatment is still the backbone of current hepatitis C therapy and is associated with bone marrow suppression and an increased risk of infections. The aim of this retrospective cohort study was to assess the risk of infections during interferon-based treatment among patients with chronic HCV infection and advanced hepatic fibrosis and its relation to treatment-induced neutropenia. METHODS This cohort study included all consecutive patients with chronic HCV infection and biopsy-proven bridging fibrosis or cirrhosis (Ishak 4-6) who started treatment between 1990 and 2003 in five large hepatology units in Europe and Canada. Neutrophil counts between 500/μL-749/μL and below 500/μL were considered as moderate and severe neutropenia, respectively. RESULTS This study included 723 interferon-based treatments, administered to 490 patients. In total, 113 infections were reported during 88 (12%) treatments, of which 24 (21%) were considered severe. Only one patient was found to have moderate neutropenia and three patients were found to have severe neutropenia at the visit before the infection. Three hundred and twelve (99.7%) visits with moderate neutropenia and 44 (93.6%) visits with severe neutropenia were not followed by an infection. Multivariable analysis showed that cirrhosis (OR 2.85, 95%CI 1.38-5.90, p=0.005) and severe neutropenia at the previous visit (OR 5.42, 95%CI 1.34-22.0, p=0.018) were associated with the occurrence of infection, while moderate neutropenia was not. Among a subgroup of patients treated with PegIFN, severe neutropenia was not significantly associated (OR 1.63, 95%CI 0.19-14.2, p=0.660). CONCLUSIONS In this large cohort of patients with bridging fibrosis and cirrhosis, infections during interferon-based therapy were generally mild. Severe interferon-induced neutropenia rarely occurred, but was associated with on-treatment infection. Moderate neutropenia was not associated with infection, suggesting that current dose reduction guidelines might be too strict.