Search

The quality of life of the HIV-infected population in developed countries has substantially improved over the years. Accordingly, the clinical limitations in the surgical treatment of the HIV-infected patients are becoming fewer, and the number of HIV-infected patients undergoing surgical interventions of all types is increasing. However, available data on the incidence and risk factors for post-surgical complications, such as surgical site infections (SSI), in HIV-infected patients are still limited and often controversial. The aim of this study was to determine the incidence and the associated risk factors for SSI in HIV-infected patients.A 1-year observational prospective multicenter surveillance study was conducted in 11 Italian Infectious Diseases Clinical Centers from which 305 consecutive HIV-infected patients undergoing different surgical procedures were enrolled. Postdischarge surveillance was conducted within 30 days after surgery. A number of variables were included in a multivariate analysis aimed at assessing potential risk factors for SSI, including body mass index, diabetes, Hepatitis C (HCV) and hepatitis B virus infection, lipodistrophy, HIV viral load, CD4 cell count and white blood cell count, preoperative hospital stay, National Nosocomial Infection Surveillance (NNIS) risk score, and any antimicrobial prophylaxis.SSI occurred in 29 of 305 (9.5%) patients, of which 17 (58.6%) SSI occurred during hospital stay, and 12 (41.4%) occurred during the postdischarge period. The SSI of the 29 patients were classified as superficial (21, 72.4%), deep (four, 13.8%), organ/space (one, 3.4%), and sepsis (three, 10.3%). Nearly 50% of the superficial and 50% of the deep SSI occurred during the postdischarge period. Organ/space infection and sepsis accounted for 13.7% of all SSI and were observed during the in-hospital stay. The multivariate analysis revealed that HCV co-infection was significantly associated to SSI occurrence. Total hospital stay was longer among patients with SSI than among those without SSI (p = 0.041).Although 92.5% of our HIV-infected patients presented a NNIS scoreor = 1, the SSI rate was twofold higher than that reported in Italian and European studies for the general population, with more severe clinical presentations. This is the first report of an association between HCV-HIV co-infection and SSI occurrence. Additionally, the viro-immunological status of our patients was not related to SSI occurrence, which suggests the need for further research for other potential risk factors that may be implicated in the occurrence of SSI.

Background: The multidrug-resistant (MDR) Acinetobacter baumannii calcoaceticus complex (Abc) has emerged as an important cause of nosocomial infections. The aims of the study were to evaluate risk factors for MDR-Abc in intensive care units (ICUs) as well as in medical and surgical wards, to define the likelihood ratios (LRs) of risk factors and to determine if risk factors differ depending on whether colonization or infections are considered. Methods: Two prospective matched case‐control studies were performed. MDR-Abc was defined as a strain resistant to four or more classes of antibiotics. The two case groups included patients with MDR-Abc infections or colonization. Controls were selected among patients not harbouring Abc. Matching criteria were the number of days from admission to MDR-Abc isolation among cases and the duration of hospitalization among controls. Results: Overall, 514 patients were included in the study. One hundred and thirty-seven patients were infected and 120 colonized. A Charlson score >3 and previous methicillin-resistant Staphylococcus aureus isolation and b-lactam use were independent risk factors for colonization and infection. Bedridden status and previous ICU admission were associated with colonization, while the presence of a central venous catheter and surgery were related to infection. The analysis of LRs showed an association between the presence of more than two risk factors and colonization or infection. The highest predicting value was observed for the presence of more than two risk factors and colonization in patients with no history of ICU admission. Conclusions: This study provides novel information that can be used to identify interventions for different stages of the spread of MDR-Abc.

International guidelines suggest that a high prevalence of meticillin-resistant Staphylococcus aureus (MRSA) infections should influence the use of vancomycin for surgical prophylaxis. In order to compare the efficacy and adverse effects of vancomycin versus cefazolin as antimicrobial prophylaxis for insertion of cerebrospinal fluid (CSF) shunts, a randomised prospective clinical trial was performed. Over a 16-month period, all consecutive adult patients who underwent CSF shunt insertion at a university hospital with a high prevalence of MRSA infections were included. Patients were randomly allocated to receive either vancomycin or cefazolin before surgery and followed-up for four weeks for the development of infections. Of the 176 patients included in the study, 88 received vancomycin and 88 cefazolin. Shunt infections were significantly less likely to be observed in patients who were on vancomycin prophylaxis (4% vs 14%; P=0.03). All isolated staphylococci were resistant to meticillin. Mortality of patients with post-surgical infections was higher in the cefazolin group (P=0.02). Our data suggest that use of vancomycin as prophylactic agent for cerebrospinal shunt placement reduces the rate of shunt infections in the context of high prevalence of MRSA.

Staphylococcus aureus bloodstream infection (BSI) contributes significantly to the morbidity and mortality of in-patients. The optimal therapy for methicillin-susceptible S. aureus BSI consists of penicillins. The efficacy of these drugs is well documented from several published data and supported from a long clinical experience. Methicillin-resistant S. aureus (MRSA) strains are responsible for the majority of nosocomial BSI and are recovered with increasing frequency at hospital admission. Although glycopeptides still represent the drugs of choice, there are several concerns on the treatment of MRSA BSI: reports of clinical failure with vancomycin treatment, regardless of the in vitro susceptibility; increasing reports of MRSA strains with reduced vancomycin susceptibility; difficulty in therapeutic dosage monitoring of teicoplanin; lack of evidence on the efficacy of combination therapy. Recently, new drugs have been introduced in the therapeutic arsenal for MRSA infections, but their clinical use is not yet clearly established for BSI. The review summarises evidence on present therapeutic options for the treatment of S. aureus BSI.

Transmission of vancomycin-resistant enterococci (VRE) can occur through direct contact with colonised or infected patients or through indirect contact via the hands of health-care workers (HCWs), or via contaminated patient care equipment or environmental surfaces. Antibiotic exposure plays an important role in the transmission dynamic of VRE. Until now, the control measures aimed at reducing the incidence of VRE colonisation and infection in hospitals have included: education of HCWs with implementation of hand-washing practices and compliance; wide and targeted surveillance cultures; isolation of VRE-positive patients; pre-emptive isolation of high-risk patients; and restriction of antibiotic use. However, despite these, VRE is still endemic in many hospitals. The causes of this could be non-compliance with infection control interventions, overuse of antibiotics, and insensitive microbiological methods for detecting VRE in stool. A scoring system using point values has been demonstrated to be useful in reducing rates of nosocomial VRE colonisation. Future prospective comparative studies of infection control approaches in different epidemiological situations might be useful.

Risk-scoring systems are utilised in patients with bloodstream infections (BSI) to quantify disease-associated morbidity and mortality based on simple clinical or laboratory data usually obtained early in the course of illness. In order to reduce BSI-associated mortality, specific scores were elaborated to allow early diagnosis and prompt and appropriate antibiotic therapy. Risk scoring was also successfully derived and validated to identify patients at higher risk for antibiotic-resistant BSI, or colonisation, mainly due to methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. However, a major limitation of risk-scoring systems is the relevance to the local epidemiological environment and the difficulty in generalising results from a single study. Intelligence technology recently utilised scores to predict risks for specific pathogens causing BSI. An example of this innovation, the TREAT system, was able to significantly reduce mortality, length of hospitalisation and costs in patients with BSI. New randomised clinical trials are needed to study the efficacy of clinical scores in reducing BSI-associated morbidity and mortality.

Background: Prediction of bacterial infections and their pathogens allows for early, directed investigation and treatment. We assessed the ability of TREAT, a computerized decision support system, to predict specific pathogens. Methods: TREAT uses data available within the first few hours of infection presentation in a causal probabilistic network to predict sites of infection and specific pathogens. We included 3529 patients (920 with microbiologically documented infections) participating in the observational and interventional trials of the TREAT system in Israel, Germany and Italy. Discriminatory performance of TREAT to predict individual pathogens was expressed by the AUC with 95% confidence intervals. Calibration was assessed using the Hosmer-Lemeshow goodness-of-fit statistic. Results: The AUCs for Gram-negative bacteria, including Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella spp. and Escherichia coli, ranged between 0.70 and 0.80 (all significant). Adequate calibration was demonstrated for any Gram-negative infection and individual bacteria, except for E. coli. Discrimination and calibration were acceptable for Enterococcus spp. (AUC 0.71, 0.65-0.78), but not for Staphylococcus aureus (AUC 0.63, 0.55-0.71). The few infections caused by Candida spp. and Clostridium difficile were well predicted (AUCs 0.74, 0.54-0.95; and 0.94, 0.88-1.00, respectively). The coverage with TREAT's recommendation exceeded that observed with physicians' treatment for all pathogens, except Candida spp. Conclusions: TREAT predicted individual pathogens causing infection well. Prediction of S. aureus was inferior to that observed with other pathogens. TREAT can be used to triage patients by the risk for specific pathogens. The system's predictions enable it to prescribe appropriate antibiotic treatment prior to pathogen identification.

Bloodstream infections (BSIs) are the third most common nosocomial infections. Catheters and other medical devices are the first exogenous causes of preventable infections in hospital. The estimated attributable mortality for catheter-associated BSI ranges from 1–35%, mainly depending on etiological agents and underlying disease. In considering this, it is necessary to reduce central venous catheter- (CVC)-related BSI prevalence and to obtain a rapid and accurate method for an early diagnosis. This review indicates the advantages and the disadvantages of old and new tools for the early diagnosis of CVC-related BSIs.

Despite the high prevalence of meticillin-resistant Staphylococcus aureus (MRSA) infections among the elderly, outcomes of nosocomial MRSA bloodstream infections (BSI) for this patient population have not been fully examined. We performed a case-control study to compare outcomes of hospital-acquired MRSA BSI among patients/=65 years of age (cases) with those younger than 65 years of age (controls). In a 430-bed tertiary-care teaching hospital, 100 hospitalized patients/=18 years of age with S. aureus BSI were included in the study. Measurements obtained were: comorbidities, severity of illness at presentation, antibiotic therapy, haematogenous complications and mortality. Overall mortality was significantly higher among cases than controls [36% vs 12%; odds ratio (OR) 4.1, 95% confidence interval (CI) 1.4-14, P0.01]. A pulmonary source was identified more frequently among elderly patients compared with younger controls (34% vs 16%; OR 2.7, 95%CI 1.1-8.1, P=0.04). On logistic regression, the following variables were independently associated with MRSA BSI among elderly patients: admission to a medical ward (OR 3.1, 95%CI 1.3-7.6, P=0.02), non-central-venous-catheter-related BSI (OR 3, 95%CI 1.2-7.6, P=0.02) and death (OR 3.7, 95%CI 1.3-11, P=0.02). Among patients who received vancomycin, more cases were treated with a reduced dose of vancomycin due to renal insufficiency compared with controls (64% vs 31%; OR 4, 95%CI 2-9, P=0.01). These data suggest that MRSA BSI is associated with significant mortality among the elderly population. Preventing MRSA acquisition among this patient population is of paramount importance.

Background: Appropriate antibiotic treatment decreases mortality, while superfluous treatment is associated with antibiotic resistance. We built a computerized decision support system for antibiotic treatment (TREAT) targeting these outcomes. Methods: Prospective cohort study comparing TREAT’s advice to physician’s treatment followed by a cluster randomized trial comparing wards using TREAT (intervention) versus antibiotic monitoring without TREAT (control). We included patients suspected of harbouring bacterial infections in three hospitals (Israel, Germany and Italy). The primary outcome, appropriate antibiotic treatment, was assessed among patients with microbiologically documented infections (MDI). Length of hospital stay, adverse events, mortality (interventional trial) and antibiotic costs (both studies), including costs related to future antibiotic resistance, were compared among all included patients. Results: Among 1203 patients included in the cohort study (350 with MDI), TREAT prescribed appropriate empirical antibiotic treatment significantly more frequently than physicians (70% versus 57%, P < 0.001) using less broad-spectrum antibiotics at half physicians’ antibiotic costs. The randomized trial included 2326 patients, 570 with MDI. The rate of appropriate empirical antibiotic treatment was higher in intervention versus control wards [73% versus 64%, odds ratio (OR): 1.48, 95% confidence interval (CI): 0.95–2.29, intention to treat, adjusted for location and clustering]. For patients treated according to TREAT’s advice in intervention wards, the difference with controls was highly significant (OR: 3.40, 95% CI: 2.25–5.14). Length of hospital stay, costs related to future resistance and total antibiotic costs were lower in intervention versus control wards. Conclusions: TREAT improved the rate of appropriate empirical antibiotic treatment while reducing antibiotic costs and the use of broad-spectrum antibiotic treatment.

Several lines of evidence suggest there is a causal association between the use of antimicrobial agents and the prevalence of antimicrobial resistance in hospitalacquired bacterial pathogens [1, 2]. However, recently published works have indicated the magnitude of the association may be lower than that previously observed and that many other variables, such as patient factors may be responsible for the development of antimicrobial resistance [3, 4]. The specific goals of this study were (1) to estimate antimicrobial resistance rates for four epidemiologically important pathogens causing bloodstream infections (BSI), (2) to compare the antimicrobial resistance rates with the hospital’s antibiotic consumption data, and (3) to determine a possible relationship between the use of antimicrobial agents and the prevalence of drug resistance in these microorganisms. The participating hospitals were partners in the TREAT project, financed by the European Community (EC, 5th Framework, 1999) and focusing on the application of an electronic decision support system to reduce antimicrobial resistance in hospitalised patients [5] This multicentre study was conducted at Freiburg University Hospital, Freiburg, Germany; Rabin Medical Center, Tel Aviv (Petah Tiqva), Israel; Aalborg Hospital, Aalborg, Denmark; and Catholic University Hospital, Rome, Italy. Data on consumption of antibiotics (from 1998 to 2001) were supplied by the hospital pharmacies and expressed in daily defined doses (DDD) per 1,000 bed-days, as outlined by the World Health Organisation. Data on consumption of the following drugs were provided (if included in the local formulary): clindamycin, trimethoprim-sulfamethoxazole, imipenem, ampicillin, ceftazidime, cefepime, piperacillin, piperacillin-tazobactam, and gentamicin. We prospectively included, from 1998 to 2001, all consecutive non-repeat blood isolates of patients with nosocomial BSI according to the definition given by the Centers for Disease Control and Prevention (Atlanta, GA, USA). Mixed cultures were excluded. Selected isolates from patients with bacteraemia included Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Microorganisms were identified using standard methods. Trends in resistance and the possible correlation between resistance and consumption were analysed using the logit regression line. Antimicrobial consumption patterns varied widely at the four sites. The most frequently prescribed drugs (>40 DDD per 1,000 bed-days) were ampicillin and gentamicin in Denmark and Israel and ceftazidime in Germany and Italy. Eur J Clin Microbiol Infect Dis (2006) 25:815–817 DOI 10.1007/s10096-006-0211-2

OBJECTIVE: To evaluate the risk factors associated with the emergence of fluconazole resistant Candida spp. in HIV-infected patients with oral candidiasis. METHODS: Candida spp. were isolated from oral swabs and tested in vitro for resistance to fluconazole. The factors potentially correlated with vazole-resistent Candida spp. infections were investigated. RESULTS: Fifty-one out of 118 patients (43%) with oral candidiasis had fluconazole resistant Candida spp. The following factors were significantly associated with the development of fluconazole resistance: (1) more than five episodes of oral candidiasis in the previous year (P < 0.001); (2) fluconazole therapy in the previous 6 months (P < 0.001); (3) C3 category of HIV infection (P< 0.001); and (4) low number of TCD4+ cells (

Background. Prediction of bloodstream infection at the time of sepsis onset allows one to make appropriate and economical management decisions. Methods. The TREAT computerized decision-support system uses a causal probabilistic network, which is locally calibrated, to predict cases of bacteremia. We assessed the system's performance in 2 independent cohorts that included patients with suspected sepsis. Both studies were conducted in Israel, Italy, and Germany. Data were collected prospectively and were entered into the TREAT system at the time that blood samples were obtained for culture. Discriminative power was assessed using a receiver-operating characteristics curve. Results. In the first cohort, 790 patients were included. The area under the receiver-operating characteristics curve for prediction of bacteremia using the TREAT system was 0.68 (95% confidence interval [CI], 0.63-0.73). We used TREAT's prediction values to draw thresholds defining a low-, intermediate-, and high-risk groups for bacteremia, in which 3 (2.4%) of 123, 62 (12.8%) of 483, and 55 (29.9%) of 184 patients were bacteremic, respectively. In the second cohort, 1724 patients were included. The area under the receiver-operating characteristics curve was 0.70 (95% CI, 0.67-0.73). The prevalence of bacteremia observed in the low-, intermediate-, and high-risk groups defined by the first cohort were 1.3% (4 of 300 patients), 13.2% (150 of 1139 patients), and 28.1% (80 of 285 patients), respectively. The low-risk groups in the 2 cohorts comprised 15%-17% of all patients. Performance was stable in the 3 sites. Conclusions. Using variables available at the time that blood cultures were performed, the TREAT system successfully stratified patients on the basis of the risk for bacteremia. The system's predictions were stable in 3 locations. The TREAT system can define a low-risk group of inpatients with suspected sepsis for whom blood cultures may not be needed.

A retrospective case-control study was performed to analyze hospital-acquired candidemia in HIV-positive patients. To understand the impact of Highly Active Antiretroviral Therapy (HAART) on the incidence of nosocomial candidemia, two time periods were compared: A (1992-1996) and B (1997-2001). 32 out of 38 (84%) cases of candidemia were hospital-related. A significant reduction in the incidence of all cases of hospital-acquired candidemia has been observed in the post-HAART in respect to pre-HAART period (0.09 episodes vs. 1.1 per 100/py). Multivariate analysis showed that the presence of central venous catheter was the only variable independently associated with the development of nosocomial candidemia. The overall mortality rate was 59%. Univariate analysis indicated three prognostic indicators: presence of concomitant opportunistic infections, isolation of non-albicans Candida species; neutropenia. Multivariate analysis of prognostic indicators showed that isolation of non-albicans Candida species is the only independent variable. Despite the use of HAART, this disease still represents a severe complication of advanced stage of AIDS.

Background. The goal of this study was to develop a validated prediction rule for identification of patients harboring vancomycin-resistant enterococci (VRE) at hospital admission. Methods. A model for the prediction of patients harboring VRE at admission was created and validated by assigning weighted point values to independent risk factors associated with harboring VRE at admission, in 2 different cohorts of patients from 2 tertiary care hospitals in Boston, Massachusetts. Patients with VRE isolated from clinical culture samples collected within 48 h of hospital admission were compared with patients not harboring VRE. To assess the diagnostic accuracy of the prediction rule, the main outcome measures were patient demographic characteristics, comorbid illnesses, hospitalizations, and antibiotic exposure. Results. A total of 412 patients were enrolled. A risk index score was derived by using the following 6 independent risk factors associated with VRE recovery within 48 h of hospital admission: previous isolation of methicillin-resistant Staphylococcus aureus (MRSA), whether the patient was receiving long-term hemodialysis, transfer from a long-term care facility, antibiotic exposure, prior hospitalization, and age >60 years. On the basis of a point score ≥10, the sensitivity, specificity, and positive and negative predictive values of this prediction rule were 44%, 98%, 81%, and 90%, respectively. Conclusions. This validated clinical prediction rule provides a novel strategy for the identification of patients at high risk of harboring VRE at hospital admission. Implementation of this rule may reduce the influx of VRE into health care institutions and the overall prevalence of VRE, by targeting VRE-screening measures and contact isolation precautions for these high-risk patients.

Background Diagnosis of HIV infection is recently occurring with increasing frequency in middle-aged and in older individuals. As HAART became available, a minimal beneficial effect on immunological outcome in older in respect of younger subjects has been reported. In fact, both the intensity and the rapidity of the immunological response appeared to be reduced in elderly subjects. On the contrary, only few reports have indicated a similar immunological outcome both in older and younger HIV-positive subjects. Interestingly, older age did not seem to significantly affect the long-term virological outcome of HAART treated subjects. Methods To characterise epidemiological and clinical features of older HIV+ subjects, a prospective case-control study was performed: 120 subjects ≥ 50 and 476 between 20 and 35 years were initially compared. Subsequently, to better define the impact of HAART on their viro-immunological response, 81 older were compared with 162 younger subjects. Results At baseline cases presented significantly lower TCD4+ cell number and were more frequently affected by comorbid conditions. Under HAART a statistically significant increase in TCD4+ cell number was observed in cases and controls. At multivariate analysis, there was no statistically significant difference between cases and controls regarding viro-immunological response. Conclusions Although older subjects present a more severe HIV infection, they can achieve, under HAART, the same viro-immunological success as the younger individuals.

Highly active anti-retroviral therapies (HAART) with human immunodeficiency virus (HIV) protease inhibitors (PIs) or nonnucleoside reverse-transcriptase inhibitors (NNRTI) were compared for their effect on prevalence, aspartyl proteinase (Sap) production and the biotypes and anti-mycotic sequential susceptibility of Candida spp. isolates from the oral cavity in a longitudinal prospective study. HAART-PI, but not HAART-NNRTI strongly inhibited Sap expression in the oral cavity without exerting any consistent effect on the role of Candida spp. isolation or selection of low virulence or anti-mycotic resistant fungus biotype. More importantly, the sequential isolates of Candida albicans from HAART-PI, but not those from suspended HAART-NNRTI, showed an increased Sap production in vitro. While further demonstrating that HIV-PI inhibit Sap expressions, our results do not support the view that the mentioned inhibition could eliminate Candida or its selection of the oral cavity.

Higher levels of soluble adhesion molecules have been found before the introduction of highly active antiretroviral therapy (HAART) in HIV-positive compared with HIV-negative patients. To evaluate the impact of HAART on endothelial function we measured the plasmatic concentrations of soluble adhesion molecules in 120 HIV-positive patients. Concentrations of P-selectin and fibrinolytic factors were significantly higher in HAART patients, whereas soluble intercellular adhesion molecule-1 did not differ significantly. HAART may induce an activation of endothelial function both directly and indirectly through lipid alterations.

We performed 2 case-control studies among 108 patients with true coagulase-negative staphylococcal (CoNS) bacteremia diagnosed within 48 h of hospital admission. Seventy-nine patients (73%) with methicillin-resistant (MR) CoNS bacteremia and 29 patients (27%) with methicillin-susceptible (MS) CoNS bacteremia were compared with 79 randomly selected control patients without CoNS bacteremia. The presence of a central venous catheter was an independent risk factor for both MR- and MS-CoNS bacteremia (P

To the Editor: Multidrug-resistant (MDR) Pseudomonas aeruginosa bloodstream infection has been described only in patients with cystic fibrosis (1) and in isolated outbreaks in intensive-care unit (ICU) or neoplastic patients (2–4). We investigated the percentage and clinical findings of patients with P. aeruginosa bacteremia having MDR strains in a 1,700-bed university hospital in Rome, Italy, over a 10-year period (1990-1999). All consecutive patients with the first episode of community- or hospital-acquired P. aeruginosa bacteremia, according to the definition of the Centers for Disease Control and Prevention (5), were included in the analysis. The term MDR P. aeruginosa covered resistance to ciprofloxacin, ceftazidime, imipenem, gentamicin, and piperacillin. In patients with P. aeruginosa bacteremia, we evaluated age, gender, type of infection (hospital or community acquired), duration of hospitalization, risk factors, clinical findings, and outcome. Prognosis immediately before bacteremia developed was determined with the revised Acute Physiology and Chronic Health Evaluation (APACHE) III system (6). Bacteria were identified by using API 20NE (Biomerieux, Marcy-l’Etoile, France). MICs were determined by broth microdilution in accordance with the methods of the National Committee for Clinical Laboratory Standards. Contingency data were analyzed by the two-tailed chi-square test or Fisher's exact test, and continuous data were analyzed by Student t test. Logistic regression analysis was used to determine which risk factors were independently significant. All statistical analysis was performed with the software program Statistics (Windows Systat Inc., Evanston, IL). In the study period, P. aeruginosa was isolated from 358 of 379,190 hospitalized patients. Among 358 patients with P. aeruginosa bacteremia, 133 (37%) were hospitalized in medical wards, 103 (29%) in ICUs, 97 (27%) in surgical wards, and 25 (7%) in neonatology; 45 (12%) had HIV infection and 28 (8%) had hematologic malignancies. For the study period, the overall hospital incidence of both nosocomial and community-acquired P. aeruginosa bacteremia was 0.94 per 1,000 hospital admissions. In particular, the incidence increased from 9.7 to 24.7 per 1,000 hospital admissions (p

Chloroquine retinopathy (CR) is a major complication of long-term malaria prophylaxis (LTMP) causing permanent visual dysfunction and occasionally blindness. After an extensive review of the published accounts of CR, we concluded that the risk of retinopathy in subjects receiving LTMP is limited to a cumulative dose that does not exceed 140 g. We present a case of CR that occurred after 8 years of malaria prophylaxis with chloroquine at a cumulative dose of 125 g. Because a threshold dose of chloroquine for retinal toxicity has not been established, careful, ongoing screening is required, especially as the cumulative dose increases.

The presented study examined the incidence, risk factors and outcome of nosocomial bacterial pneumonia (NBP) in human immunodeficiency virus (HIV)-infected subjects. Forty-two cases of NBP were ascertained by a 5-yr prospective surveillance and were matched to 84 controls. NBP incidence was 10.8 per 10,000 hospital patient-days. In particular, the incidence of NBP was 13.9 per 10,000 patient-days in the period 1994–1996 and 5.6 per 10,000 patient-days in the period 1997–1998 (p=0.01).By using regression analysis, predictors for developing NBP were an increasing value of Acute Physiology and Chronic Health Evaluation (APACHE) III score (pNosocomial bacterial pneumonia is more common in patients with advanced human immunodeficiency virus infection, high Acute Physiology and Chronic Health Evaluation III score and central nervous system diseases. Although the incidence of nosocomial bacterial pneumonia, as well of other opportunistic infections, decreased considerably in the era of highly active antiretroviral therapy, it still represents an important cause of mortality.

The aim of the study was to assess the incidence of hospital and community acquired bacterial pneumonia in HIV-infected subjects prior to and after the introduction of highly active antiretroviral therapy (HAART). We studied 266 patients with bacterial pneumonia over two separate periods, 154 in the first period and 112 in the second period. A statistically significant difference in the incidence of bacterial pneumonia in the two study periods was observed ranging from 13.1 to 8.5 episodes per 100 persons. The incidence of community-acquired bacterial pneumonia decreased from 10.7 to 7.7 ( P =0.01), while that of nosocomial episodes decreased from 2.4 to 0.8 episodes ( P =0.003). Low levels of peripheral CD 4+ cells ( 3 ) and intravenous drug abuse (IVDA) were significantly associated with the development of community-acquired bacterial pneumonia, while an increasing value of APACHE III score and prolonged hospitalisation increased the risk of nosocomial bacterial pneumonia in both study periods.

To evaluate the changing characteristics of HIV-associated bacteremia in the highly active antiretroviral therapy (HAART) era, we conducted a prospective case control study, comparing two periods of time, before (period A) and after (period B) the introduction of HAART. In total, 174 patients with bacteremia and 348 controls were studied. By comparing incidence in periods A and B, a statistically significant reduction of bacteremia, from 11.8 to 6.3/100 person-years (PY), was observed (p = .0001). Incidence of hospital-acquired bacteremia decreased from 5.8 episodes/100 PY in period A to 2.4/100 PY in period B (p = .0005). A similar trend was also observed for community-acquired episodes of bacteremia, with a value close to statistical significance. Logistic regression analysis indicated that intravenous drug abuse, central venous catheter (CVC) use, high value on APACHE III score, and neutropenia were independent risk factors for bacteremia in both the study periods. Interestingly, comparing the prevalence of bacteremia risk factors in the two study periods, we observed a significant reduction in the use of CVC (p = .04, period A versus period B) and in neutropenia (p = .04). The crude mortality rate was 31% in period A and 23% in period B (p = not significant [ns]). Logistic regression analysis indicated that an high value of Acute Physiology and Chronic Health Evaluation III (APACHE III) score (p < .001) predicted an increased risk of death. Analysis of prognostic factors of bacteremia did not significantly differ in both the study periods. We conclude that HAART has determined a significant reduction of the incidence and a modification of the characteristics of bacteremia. This reduced incidence may produce a substantial impact on future morbidity and health care costs of patients with HIV.

The purpose of this study was to characterise the epidemiological and the clinical features of non-AIDS-defining neoplasms (NAN) in HIV-infected subjects in the era of highly active antiretroviral therapy (HAART). A retrospective cohort of 4,041 subjects was established. Patients were recruited from January 1989 to December 1998. We observed 51 NAN over the study period. The overall incidence rate was 0.21 per 100 person-years (PY) and it remained stable, also after the introduction, in 1996 of HAART. Moreover, stratifying according to the type of neoplasms there was no statistically significant difference in the incidence of NAN over the study period. While the epidemiological features of NAN generally was not different from that observed in immunocompetent individuals, the neoplasms had a more aggressive clinical course and a poor prognosis. Survival analysis showed that the presence of NAN significantly reduced the survival of patients with AIDS (P=0.01; OR=0.62; 95% CI=0.47-0.96) compared with matched controls. The overall mortality-rate was 63% with an incidence rate of 0.13 per 100 PY. Although the incidence rate of NAN is not of great magnitude, as the number of HIV-infected individuals continues to increase and their survival improves, the number of HIV-infected subjects with NAN might consequently increase as well as the related morbidity and mortality.

Highly active antiretroviral therapy that includes human immunodeficiency virus (HIV) aspartyl protease inhibitors (PIs) causes a decline in the incidence of some opportunistic infections in AIDS, and this decline is currently attributed to the restoration of specific immunity. The effect of two PIs (indinavir and ritonavir) on the enzymatic activity of a secretory aspartyl protease (Sap) of Candida albicans (a major agent of mucosal disease in HIV-infected subjects) and on growth and experimental pathogenicity of this fungus was evaluated. Both PIs strongly (>/=90%) and dose dependently (0.1-10 microM) inhibited Sap activity and production. They also significantly reduced Candida growth in a nitrogen-limited, Sap expression-dependent growth medium and exerted a therapeutic effect in an experimental model of vaginal candidiasis, with an efficacy comparable to that of fluconazole. Thus, besides the expected immunorestoration, patients receiving PI therapy may benefit from a direct anticandidal activity of these drugs.

Patients with acquired immune deficiency syndrome (AIDS) are at increased risk for pneumothorax, which usually occurs in the setting of Pneumocystis carinii pneumonia. The rationale of the present study was based on the hypothesis that the increased incidence of pulmonary tuberculosis in human immunodeficiency virus (HIV)-infected patients could favour the development of pneumothorax in such patients. A case-control study was performed comprising 140 HIV-infected patients grouped as follows: 35 patients with pneumothorax and 105 matched controls without pneumothorax. Univariate analysis identified four risk factors for pneumothorax: 1) previous P. carinii pneumonia (p=0.01); 2) current P. carinii pneumonia (p=0.02); 3) pulmonary tuberculosis (p=0.01); and 4) cysts, pneumatoceles or bullae on chest radiographs (p

The objective of this study was to identify the prognostic factors influencing the outcome of aspergillosis in two models of immunodeficiency, namely haematological malignancies and HIV infection. The study is based on a 5 year prospective logistic regression analysis of risk factors, clinical features, radiological findings and therapy affecting the prognosis of aspergillosis in 43 patients, i.e. 27 haematological neoplastic patients (group A) and 16 HIV infected patients (group B). Univariate analysis indicated that neutropenia ( P = 0.02), haemoptysis ( P = 0.03) and concomitant AIDS ( P = 0.02) negatively influenced the prognosis of aspergillosis. Comparing the two groups of patients, significant differences emerged in the prognostic indicators. In particular respiratory failure ( P = 0.02) and radiological bilateral involvement of the lungs were associated with a poor prognosis in group A ( P = 0.04) and low ( 3 ) T CD4 + cell count in group B ( P = 0.02). At variance, a better prognosis was documented in patients treated with sequential therapy (amphotericin B and itraconazole) only within the group of haematological patients ( P = 0.003). On multivariate analysis sequential therapy ( P = 0.01) and AIDS ( P = 0.03) were independent prognostic indicators of aspergillosis. In conclusion, our prospective study indicates that aspergillosis, although an uncommon event in patients with HIV infection, has a more severe prognosis in comparison to haematological patients. Future prospective clinical trials are necessary to confirm the real importance of the sequential therapy, with amphotericin B and itraconazole, in patients with aspergillosis.

In the present study we analyze peripheral blood lymphocytes (PBL) from patients with human immunodeficiency virus (HIV) infection for both phenotypic expression and function of P-glycoprotein (P-170). This transmembrane efflux pump is known to be one of the mechanisms responsible for the multidrug resistance (MDR) in cancer therapy and it is also constitutively expressed in normal PBL. P-170 function, evaluated as Rhodamine 123 (Rh123) efflux in flow cytometry, was found to be significantly reduced in CD16+ natural killer (NK) cells from patients with HIV infection. Interestingly, this reduced efflux significantly correlates with the decreased NK cytotoxicity observed in HIV+ patients, as evaluated against the NK-specific K562 target cell line. These results support a possible role of the P-170-related pump in specific immunological lymphocyte function such as NK cell-mediated cytotoxicity.

Objective In 2009, in a European survey, around a quarter of Europeans reported witnessing discrimination or harassment at their workplace. The parity committee from the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) designed a questionnaire survey to investigate forms of discrimination with respect to country, gender and ethnicity among medical professionals in hospitals and universities carrying out activities in the clinical microbiology (CM) and infectious diseases (ID) fields. Design The survey consisted of 61 questions divided into five areas (sociodemographic, professional census and environment, leadership and generic) and ran anonymously for nearly 3 months on the ESCMID website. Subjects European specialists in CM/ID. Results Overall, we included 1274 professionals. The majority of respondents (68%) stated that discrimination is present in medical science. A quarter of them reported personal experience with discrimination, mainly associated with gender and geographic region. Specialists from South-Western Europe experienced events at a much higher rate (37%) than other European regions. The proportion of women among full professor was on average 46% in CM and 26% in ID. Participation in high-level decision-making committees was significantly (>10 percentage points) different by gender and geographic origin. Yearly gross salary among CM/ID professionals was significantly different among European countries and by gender, within the same country. More than one-third of respondents (38%) stated that international societies in CM/ID have an imbalance as for committee member distribution and speakers at international conferences. Conclusions A quarter of CM/ID specialists experienced career and research discrimination in European hospitals and universities, mainly related to gender and geographic origin. Implementing proactive policies to tackle discrimination and improve representativeness and balance in career among CM/ID professionals in Europe is urgently needed.

Background: Pharmacokinetic interaction between Vinca alkaloids and antiretrovirals has been widely demonstrated, even though its clinical relevance is still debated. The incidence of Hodgkin's lymphoma appears to be rising in HIV-infected people, and vinblastine - containing chemotherapy regimens are widely recommended in these pts. Supplement: Abstracts of the Tenth International Congress on Drug Therapy in HIV Infection http://www.biomedcentral.com/content/pdf/1758-2652-13-S4-info.pdf Conference: Tenth International Congress on Drug Therapy in HIV Infection 7-11 November 2010 Glasgow, UK (Published: 8 November 2010) doi:10.1186/1758-2652-13-S4-P215 Cite this article as: Cingolani et al.: Detrimental clinical interaction between ritonavir-boosted protease inhibitors and vinblastin in HIVinfected patients with Hodgkin lymphoma. Journal of the International AIDS Society 2010 13(Suppl 4):P215. Full text: PubMed Central: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3113000/

Antibiotic use in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients during the COVID-19 pandemic has exceeded the incidence of bacterial coinfections and secondary infections, suggesting inappropriate and excessive prescribing. Even in settings with established antimicrobial stewardship (AMS) programmes, there were weaknesses exposed regarding appropriate antibiotic use in the context of the pandemic. Moreover, antimicrobial resistance (AMR) surveillance and AMS have been deprioritised with diversion of health system resources to the pandemic response. This experience highlights deficiencies in AMR containment and mitigation strategies that require urgent attention from clinical and scientific communities. These include the need to implement diagnostic stewardship to assess the global incidence of coinfections and secondary infections in COVID-19 patients, including those by multidrug-resistant pathogens, to identify patients most likely to benefit from antibiotic treatment and identify when antibiotics can be safely withheld, de-escalated or discontinued. Long-term global surveillance of clinical and societal antibiotic use and resistance trends is required to prepare for subsequent changes in AMR epidemiology, while ensuring uninterrupted supply chains and preventing drug shortages and stock outs. These interventions present implementation challenges in resource-constrained settings, making a case for implementation research on AMR. Knowledge and support for these practices will come from internationally coordinated, targeted research on AMR, supporting the preparation for future challenges from emerging AMR in the context of the current COVID-19 pandemic or future pandemics.

Graphical Abstract, Highlights • Multi-Criteria Decision Analysis applied to SARS CoV-2 pandemic • Creating a model to prioritize hospitalization of COVID-19 patients in low- and middle-income countries • Eleven criteria selected considering their feasibility in low-resource settings • Reducing the risk of non-standardised approaches and improving the response of health systems to new pandemics, Objective To use Multi-Criteria Decision Analysis (MCDA) to determine weights for eleven criteria in order to prioritize COVID-19 non-critical patients for admission to hospital in healthcare settings with limited resources. Methods The MCDA was applied in two main steps: specification of criteria for prioritizing COVID-19 patients (and levels within each criterion); and determination of weights for the criteria based on experts’ knowledge and experience in managing COVID-19 patients, via an online survey. Criteria were selected based on available COVID-19 evidence with a focus on low- and middle-income countries (LMICs). Results The most important criteria (mean weights, summing to 100%), are: PaO2 (16.3%); peripheral O2 saturation (15.9%); chest X-ray (14.1%); Modified Early Warning Score-MEWS (11.4%); respiratory rate (9.5%); comorbidities (6.5%); living with vulnerable people (6.4%); body mass index (5.6%); duration of symptoms before hospital evaluation (5.4%); CRP (5.1%); and age (3.8%). Conclusions At the beginning of a new pandemic, when evidence for disease predictors is limited or unavailable and effective national contingency plans are difficult to establish, the MCDA prioritization model could play a pivotal role in improving the response of health systems.

The endemic state of methicillin-resistant Staphylococcus aureus (MRSA) occurs through a constant influx of MRSA into the healthcare setting from newly admitted MRSA-positive patients, followed by cross-transmission among inpatients and an efflux of MRSA from the hospital with discharged patients. To date, most MRSA prevention strategies have targeted cross-transmission among hospitalised patients. Intensive concerted interventions that include isolation can reduce the MRSA incidence substantially. However, debate continues about the cost-effectiveness of infection control policies, including screening protocols, to control the influx of MRSA into hospitals. The rationale and cost-effectiveness of wide screening, as compared to targeted screening, should be further studied using appropriate statistical approaches and economic modelling.