Tuberculosis screening in outpatient healthcare workers: lessons from a high-income, low TB burden country.

SETTING: Early diagnosis of latent tuberculous infection (LTBI) should be pursued in healthcare workers (HCWs). While HCWs in hospitals are screened for LTBI, HCWs in outpatient settings are usually not. In 2017, in Italy, a tuberculosis (TB) infected paediatrician working in an outpatient vaccination service infected 15 adults and nine children. The investigation involved 2490 children and 151 adults. Among children, nine were tuberculin skin test-positive, and four developed active TB. Among 123 adult contacts with longer exposure, seven were interferon-gamma release assay (IGRA) positive and none had active TB. Among 28 close contacts, eight had a positive IGRA, and three had pulmonary TB. The total outbreak cost €1 017 903.OBJECTIVE: To compare the outbreak cost with those of potential screening programme strategies.RESULTS: Regular screening of paediatric outpatient HCWs would have cost between €2592 and €11 373. Extending the screening to all outpatient HCWs (caring for adults and children) would have cost between €66 384 and €155 043. Investigating only close contacts would have cost €42 857.CONCLUSION: Each of these screening strategies would have been cost-effective compared with the outbreak investigation occurring in real life with a cut-off of 474 for the maximum number of tested outpatient HCWs needed for the screening strategy to be cost-saving.

Predictive models of surgical site infections after coronary surgery: insights from a validation study on 7090 consecutive patients.

BACKGROUND: The role of specific scoring systems in predicting risk of surgical site infections (SSIs) after coronary artery bypass grafting (CABG) has not been established. AIM: To validate the most relevant predictive systems for SSIs after CABG. METHODS: Five predictive systems (eight models) for SSIs after CABG were evaluated retrospectively in 7090 consecutive patients undergoing isolated (73.9%) or combined (26.1%) CABG. For each model, accuracy of prediction, calibration, and predictive power were assessed with area under receiver-operating characteristic curve (aROC), the Hosmer-Lemeshow test, and the Goodman-Kruskal γ-coefficient, respectively. Six predictive scoring systems for 30-day in-hospital mortality after cardiac operations were evaluated as to prediction of SSIs. The models were compared one-to-one using the Hanley-McNeil method. FINDINGS: There were 724 (10.2%) SSIs. Whereas all models showed satisfactory calibration (P = 0.176-0.656), accuracy of prediction was low (aROC: 0.609-0.650). Predictive power was moderate (γ: 0.315-0.386) for every model but one (γ: 0.272). When compared one-to-one, the Northern New England Cardiovascular Disease Study Group mediastinitis score had a higher discriminatory power both in overall series (aROC: 0.634) and combined CABG patients (aROC: 0.648); in isolated CABG patients, both models of the Fowler score showed a higher discriminatory power (aROC: 0.651 and 0.660). Accuracy of prediction for SSIs was low (aROC: 0.564-0.636) even for six scoring systems devised to predict mortality after cardiac surgery. CONCLUSION: In this validation study, current predictive models for SSIs after CABG showed low accuracy of prediction despite satisfactory calibration and moderate predictive power.

Assessment of risk factors for candidemia in non-neutropenic patients hospitalized in Internal Medicine wards: A multicenter study.

BACKGROUND: An increasing prevalence of candidemia has been reported in Internal Medicine wards (IMWs). The aim of our study was to identify risk factors for candidemia among non-neutropenic patients hospitalized in IMWs. METHODS: A multicenter case-control study was performed in three hospitals in Italy. Patients developing candidemia (cases) were compared to patients without candidemia (controls) matched by age, time of admission and duration of hospitalization. A logistic regression analysis identified risk factors for candidemia, and a new risk score was developed. Validation was performed on an external cohort of patients. RESULTS: Overall, 951 patients (317 cases of candidemia and 634 controls) were included in the derivation cohort, while 270 patients (90 patients with candidemia and 180 controls) constituted the validation cohort. Severe sepsis or septic shock, recent Clostridium difficile infection, diabetes mellitus, total parenteral nutrition, chronic obstructive pulmonary disease, concomitant intravenous glycopeptide therapy, presence of peripherally inserted central catheter, previous antibiotic therapy and immunosuppressive therapy were factors independently associated with candidemia. The new risk score showed good area under the curve (AUC) values in both derivation (AUC 0.973 95% CI 0.809-0.997, p<0.001) and validation cohort (0.867 95% CI 0.710-0.931, p<0.001). A threshold of 3 leads to a sensitivity of 87% and a specificity of 83%. CONCLUSION: Non-neutropenic patients admitted in IMWs have peculiar risk factors for candidemia. A new risk score with a good performance could facilitate the identification of candidates to early antifungal therapy.

Predictors of choice of initial antifungal treatment in intraabdominal candidiasis.

Intraabdominal candidiasis (IAC) is the second most frequent form of invasive candidiasis, and is associated with high mortality rates. This study aims to identify current practices in initial antifungal treatment (IAT) in a real-world scenario and to define the predictors of the choice of echinocandins or azoles in IAC episodes. Secondary analysis was performed of a multinational retrospective cohort at 13 teaching hospitals in four countries (Italy, Greece, Spain and Brazil), over a 3-year period (2011-2013). IAC was identified in 481 patients, 323 of whom received antifungal therapy (classified as the treatment group). After excluding 13 patients given amphotericin B, the treatment group was further divided into the echinocandin group (209 patients; 64.7%) and the azole group (101 patients; 32.3%). Median APACHE II scores were significantly higher in the echinocandin group (p 0.013), but IAT did not differ significantly with regard to the Candida species involved. Logistic multivariate stepwise regression analysis, adjusted for centre effect, identified septic shock (adjusted OR (aOR) 1.54), APACHE II >15 (aOR 1.16) and presence in surgical ward at diagnosis (aOR 1.16) as the top three independent variables associated with an empirical echinocandin regimen. No differences in 30-day mortality were observed between groups. Echinocandin regimen was the first choice for IAT in patients with IAC. No statistical differences in mortality were observed between regimens, but echinocandins were administered to patients with more severe disease. Some disagreements were identified between current clinical guidelines and prescription of antifungals for IAC at the bedside, so further educational measures are required to optimize therapies.

Epidemiology and variables involved in dental abscess: survey of dental emergency unit in Trieste.

OBJECTIVES: The objective of this epidemiologic study was to estimate the healing time of acute dental abscesses and to evaluate the main variables involved in the healing process itself. SUBJECTS AND METHODS: Among a sample of over 24 000 patients visited at the emergency dental unit, 688 subjects were diagnosed with dental abscess and enrolled in the study. Case histories of all patients were collected to investigate the clinical course and healing time of dental abscess according to anamnestic and diagnostic data and therapeutic management. A multiple logistic regression model was performed to evaluate the association of each variable with the healing time required for dental abscess. RESULTS: Variables associated with increased healing time were spring seasonality at admission, pyretic state, trismus, involvement of multiple anatomic spaces, and spontaneous drainage. Moreover, administration of some, but not all, classes of antibiotics was also associated with an increased healing time. CONCLUSIONS: The knowledge of variables involved in healing time for dental abscess is crucial in the optimization of managing such infections in terms of cost-benefit ratio. This would represent a valuable way to ensure a shortened and more effective healing.

Cholera with severe renal failure in an Italian tourist returning from Cuba, July 2013.

In July 2013, an Italian tourist returning from Cuba was hospitalised in Trieste, Italy, for cholera caused by Vibrio cholerae O1 serotype Ogawa with severe renal failure. An outbreak of cholera was reported in Cuba in January 2013. Physicians should consider the diagnosis of cholera in travellers returning from Cuba presenting with acute watery diarrhoea.

Prolonged hospitalisation for immigrants and high risk patients with positive smear pulmonary tuberculosis.

BACKGROUND AND OBJECTIVE: Tuberculosis (TB) occurring in immigrants and resistance to drugs are major problems for TB control in Western countries. Directly observed therapy (DOT) reduces disease transmission, but this approach may have poor results among illegal immigrants. Our aim was to evaluate a prolonged hospitalisation programme to improve early outcome of TB treatment in high risk patients. METHODS: All the consecutive adult patients with sputum smear-positive pulmonary TB admitted to 2 Italian referral TB Centres were evaluated. Hospital-based DOT was provided to high risk patients up-to smear conversion. Demographic, microbiological and clinical conditions, as potential factors associated with confirmed smear conversion at 60 and 90 days of anti-tuberculous therapy were evaluated. RESULTS: 122 patients were studied, 45.9% of them were immigrants (20% illegal) from high-prevalence TB countries. HIV testing was negative in all cases. Twelve patients had M. tuberculosis resistant to > or = 1 first-line anti-tuberculous agents. The rate of defaulting from TB treatment was 73%. Sputum smear became negative in 84.4% cases after 60 days and 933% cases after 90 days. At such time, smear conversion rates were similar among different high risk subgroups such as illegal immigrants (95.9%), legal foreign-born (92.5%) and Italian persons (94.8%). Persistent sputum smear positivity was independently correlated with the extent of pulmonary lesions at 60 (p < 0.0001) and 90 days (p = 0.038) of hospital-based DOT. CONCLUSIONS: These findings suggest that prolonged hospitalisation for illegal immigrants and high risk TB patients, may positively influence the early outcome of TB treatment despite of drug resistance and legal status.

[Survey on the ability to prescribe antibiotic therapy among Italian residents in geriatrics and internal medicine]. / Indagine sulla capacità deglispecializzandi in geriatriae in medicina interna diprescrivere terapia antibioticain Italia.

Antibiotic therapy is a crucial and often life-saving strategy. This study assessed the ability to prescribe antibiotic therapy among a series of Italian postgraduate students in geriatrics and internal medicine. Participants were administered an anonymous questionnaire consisting of self-assessment of their ability to prescribe antibiotics and then manage a case of community-acquired pneumonia. The Wilcoxon test for comparisons between two independent samples was used for statistical analysis. Almost half the 70 students considered their knowledge of antibiotic therapy insufficient and were not satisfied with the notions received during their studies. Indeed, the change in antibiotic therapy required to control acute exacerbation of pneumonia was correctly identified by only 36% of students. Moreover, 38% of them gave the correct answer on factors influencing the duration of antibiotic therapy in the presence of definite improvement of pneumonia. No significant difference was found between the responses of residents in geriatrics and internal medicine. Overall, our study shows that nearly half of our students think they have inadequate antibiotic prescribing skills. This is confirmed by a low ability to establish the best management of the clinical case. To repair this severe shortcoming, different training methods need to be compared and more effective forms of instruction adopted.

Autoimmune diseases and infections: controversial issues.

The etiology and pathogenesis of certain types of disease remain controversial and stand like a bridge that crosses infectious, autoimmune and autoinflammatory pathways. Infection, for example, may initiate a disease, although it is the genetic regulation in the host, the interplay between virus or bacteria persistence and autoimmunity that produces the later phases of disease, the antigenic determinants responsible for inducing autoimmune disease, and the pathogenetic effector mechanisms. Infections agents cause pericarditis, but in 85% of cases it is "idiopathic". It has also been shown that persistent Clamydia pneumoniae, Porphyromonas gingivalis, and Helicobacter pylori infections cause host immunity and promote atherogenesis. A number of infectious agents have been suggested as potential triggers for primary biliary cirrhosis. Infections and vaccinations have also been linked to the pathogenesis of fibromyalgia syndrome, a common, chronic syndrome of widespread pain. Many factors are also responsible for fever of unknown origin such as: infections, autoimmunity disease, etc. However, it is difficult to determine a direct correlation between the infections agents in such a large group of diseases. The aim of this review is to analyze some of the controversies about the role of infections in autoimmune diseases.

Serological evidence of Rickettsia infections in forestry rangers in north-eastern Italy.

The prevalence of antibodies to Rickettsiae and other tick-borne microrganisms in the sera of 181 forestry rangers from Friuli-Venezia-Giulia, Italy, was examined. Seven (3.9%) sera were positive for Rickettsia conorii and Rickettsia helvetica, as single or dual infections; four of these sera had been found previously to be positive for Borrelia burgdorferi. Antibodies to Coxiella burnetii were detected in five (2.8%) sera, four of which were also positive for B. burgdorferi. These findings indicate that patients in this north-eastern Italian region with fever subsequent to tick-bite should be investigated for Rickettsia and Coxiella infections.

Secular trends in nosocomial candidaemia in non-neutropenic patients in an Italian tertiary hospital.

A retrospective study was performed in an Italian tertiary hospital to evaluate trends in candidaemia between 1992 and 2001, and to compare the characteristics of episodes of fungaemia between 1992--1997 and 1998--2001. In total, 370 episodes of candidaemia were identified, with an average incidence of 0.99 episodes/10 000 patient-days/year (range 0.49--1.29 episodes). On an annual trend basis, the overall incidence was essentially stable in surgical and medical wards, but decreased in intensive care units (ICUs) (p 0.0065). The average use of fluconazole was 37.9 g/10 000 patient-days/year (range 21.4--56.1 g), and did not change significantly during the 10-year period. Nearly two-thirds of patients were in ICUs at the onset of candidaemia, but none was neutropenic in either study period. Candida albicans remained the predominant species isolated (53.8% vs. 48.1%), followed by Candida parapsilosis, Candida glabrata and Candida tropicalis, the distribution of which did not change significantly. The 30-day crude mortality rate was essentially similar (44% vs. 35%) in both study periods. Thus the incidence of nosocomial candidaemia, although high in this institution, decreased among critically-ill patients during the 10-year period. This finding seemed to be related to an improvement in infection control practices, particularly regarding the prevention of intravascular catheter-related infections in ICUs. Although the overall use of fluconazole was considerable, no increase in azole-resistant non-albicans Candida spp. was detected.

Seroprevalence of tick-borne infections in forestry rangers from northeastern Italy.

The aim of this study was to estimate the seroprevalence of antibodies to Borrelia burgdorferi, Anaplasma phagocitophilum and tick-borne encephalitis (TBE) virus, and risk factors, in forestry rangers from the Friuli-Venezia-Giulia region in northeastern Italy. Sera from 181 forestry rangers were examined with two-tiered serological tests for TBE, Lyme borreliosis and ehrlichiosis. Information about risk factors such as job location, residence, number of tick bites and outdoor leisure activities was collected with a questionnaire. Seropositivity was 0.6% for TBE virus, 23.2% for Lyme borreliosis and 0.6% for ehrlichiosis. Lyme borreliosis positivity, as determined by Western blot, was associated with working in the foothills, with gardening in the northeastern part of the region, and with a history of yearly tick bites. Risk factors were similar when a case of Lyme borreliosis was defined either by Western blot positivity or by clinical history.

Nosocomial cluster of Candida guillermondii fungemia in surgical patients.

A nosocomial cluster of Candida guillermondii fungemia ( n=5 episodes) occurred in a surgical unit over a 2-week period. The five infected patients had received parenteral nutrition through central lines and three of them had catheter-related candidemia. All of the isolates were resistant to 5-flucytosine (MIC >32 microg/ml) and they had strictly related fingerprints, as generated by randomly amplified polymorphic DNA analysis. Although no isolate of Candida guillermondii was recovered from other clinical, surveillance or environmental samples, nosocomial spread of this yeast stopped following the reinforcement of infection control measures. Candida guillermondii may require an intravascular foreign body to cause fungemia, but the outbreak reported here shows that it can be transmitted nosocomially and cause epidemics.

Impact of antibiotic changes in empirical therapy on antimicrobial resistance in intensive care unit-acquired infections.

We conducted a one-year prospective study on intensive care unit (ICU)-acquired infections and antimicrobial resistance patterns in an 18-bed medical-surgical ICU of a tertiary-care university hospital. We divided the study into two six-month periods in order to evaluate the impact of antibiotic changes in empirical therapy on antimicrobial resistance profiles of the principal isolated micro-organisms. In the first period no changes were made to the previously applied empirical antibiotic protocol; at the end of this period we found high rates of methicillin resistance (MR) among staphylococci, 93% for Staphylococcus aureus (69 isolates) and 79% for coagulase-negative staphylococci (CNS) (48 isolates), and of multiple drug resistance for Pseudomonas aeruginosa (57 isolates), in particular 67% resistance to piperacillin/tazobactam (PIP/TZ). We therefore decided to substitute PIP/TZ with imipenem in nosocomial pneumonia and with cefepime plus metronidazole in peritonitis. We also considered the previous use of amoxicillin/clavulanate (AM/CL) at admission in critically ill patients inadequate; we therefore advised that no antibiotics should be given unless fever developed and eventually to replace AM/CL with trimethoprim/sulfamethoxazole (TMP/SMX). At the end of this intervention period, we observed a significant decrease of S. aureus MR (93 vs. 73%, P = 0.003) and of P. aeruginosa resistance to PIP/TZ (67 vs. 29%, P < 0.001). A reduction in MR was also seen in CNS (79 vs. 64%, P = 0.09). Other resistance patterns also improved among staphylococci; in contrast P. aeruginosa resistance to imipenem increased in the second period (24 vs. 41%, P = 0.06). A non-premeditated change of antibiotics in empirical therapy, on the basis of detected resistance patterns, provided promising results in reducing some antimicrobial resistance rates. We believe, however, that antibiotic changes must be tailored to local microbiological situation monitoring, and that a repeated rotation is crucial to limit the emergence of new resistance profiles. Furthermore the adoption of this policy should be accompanied by other infection control practices aimed at reducing antimicrobial resistance and nosocomial infection rates.

[Prevalence of nosocomial infections in Intensive Care Units in Triveneto area, Italy]. / La prevalenza delle infezioni nosocomiali nelle Unità di Terapia Intensiva del Triveneto in Italia.

BACKGROUND: Nosocomial infection is one of the most common complications affecting patients admitted in intensive care units (ICU). The aim of this study is to evaluate rates of ICU-acquired infections, potential risk factors for these infections, causative microorganisms and antibiotic resistance patterns. METHODS: A 1-day point-prevalence study was conducted in 39 ICUs in Triveneto area (Italy) in November 1998. The overall study population included 188 patients with mean age of 61.4+/-19.3 years; the mean SAPS II score at entry into the ICU was 44.4+/-16.8 and the median duration of hospitalization was 9 days (range 2-636). RESULTS: A total of 59 patients (31.4%) had 79 episodes of ICU-acquired infections; pneumonia (45.5%), bloodstream infection (30.4%), and urinary tract infection (11.4%) were the most frequent types of infection. The leading causative microorganisms were S. aureus (24.4%, 77% of them were resistant to methicillin), Enterobacteriaceae (24.4%), P. aeruginosa (23.2%), fungi (12.2%), coagulase-negative staphylococci (7.3%) and Enterococcus spp (4.9%). Independent risk factors for nosocomial infections were duration of hospitalization >7 days (OR 4.29, 95% CI 1.82-10.1), SAPS II score >30 (OR 3.34, 95% CI 1.0-11.18), total parenteral nutrition (OR 2.69, 95% CI 1.19-6.07) and tracheostomy (OR 1.88, 95% CI 0.84-4.20). CONCLUSIONS: Nosocomial infections are relatively frequent in Triveneto area ICUs. The predominance of pneumonia and bloodstream infection, and the high frequency of antibiotic-resistant pathogens indicate that resources had to be assigned towards the implementation of control programs of those infections, monitoring of antibiotic resistance and prescription, and antibiotic therapy guidelines.

Nosocomial candidemia in non-neutropenic patients at an Italian tertiary care hospital.

In a retrospective study conducted in an Italian tertiary care hospital, the incidence of nosocomial candidemia was evaluated together with causative pathogens, treatment, and risk factors for death. Over a 6-year period (1992-1997), a total of 189 episodes of candidemia occurred in 189 patients (mean age 58+/-19 years), accounting for an average incidence of 1.14 episodes per 10,000 patient-days per year. The most common reasons for hospitalization were solid neoplasia (21%), trauma (17%), abdominal diseases requiring surgery (13%), and cardiovascular diseases (13%). No patient was neutropenic within 3 weeks prior to the onset of candidemia. One hundred thirty patients were hospitalized in intensive care units, 47 patients in surgical wards, and 12 patients in medical wards. Candida albicans was the most frequently isolated pathogen, accounting for 54% of fungal isolates, followed by Candida parapsilosis (23%), Candida glabrata (7%), Candida tropicalis (5%), Candida pelliculosa (4%), Candida lusitaniae (1%), Candida humicula (1%), and other non-albicans Candida spp. (5%). Seventy-six (41%) patients received adequate antifungal therapy. Seventy-one (58%) of the 123 evaluable patients with central venous catheters underwent line removal; 51 of them had catheter-related candidemia. The 30-day crude mortality rate was 45%. Older age, hospitalization in an intensive care unit, a longer duration of candidemia, retention of central lines, and inadequate antifungal therapy were significantly associated with poor outcome. In the present study, nosocomial candidemia was a frequent and relatively underestimated illness. Adequate antifungal therapy and central line removal independently reduced the high mortality of the disease.

Treatment of low back pain exacerbations with willow bark extract: a randomized double-blind study.

PURPOSE: Herbal medicines are widely used for the treatment of pain, although there is not much information on their effectiveness. This study was designed to evaluate the effectiveness of willow (Salix) bark extract, which is widely used in Europe, for the treatment of low back pain. SUBJECTS AND METHODS: We enrolled 210 patients with an exacerbation of chronic low back pain who reported current pain of 5 or more (out of 10) on a visual analog scale. They were randomly assigned to receive an oral willow bark extract with either 120 mg (low dose) or 240 mg (high dose) of salicin, or placebo, with tramadol as the sole rescue medication, in a 4-week blinded trial. The principal outcome measure was the proportion of patients who were pain-free without tramadol for at least 5 days during the final week of the study. RESULTS: The treatment and placebo groups were similar at baseline in 114 of 120 clinical features. A total of 191 patients completed the study. The numbers of pain-free patients in the last week of treatment were 27 (39%) of 65 in the group receiving high-dose extract, 15 (21%) of 67 in the group receiving low-dose extract, and 4 (6%) of 59 in the placebo group (P <0.001). The response in the high-dose group was evident after only 1 week of treatment. Significantly more patients in the placebo group required tramadol (P <0.001) during each week of the study. One patient suffered a severe allergic reaction, perhaps to the extract. CONCLUSION: Willow bark extract may be a useful and safe treatment for low back pain.

Role of brain biopsy in the management of focal brain lesions in HIV-infected patients. Gruppo Italiano Cooperativo AIDS & Tumori.

In this multicenter, retrospective study of 160 brain biopsies in the assessment of HIV-related focal brain lesions, diagnostic sensitivity was acceptable (87%), but the procedure carried considerable morbidity (7.5%) and mortality (3.1%). Moreover, it is not always possible to initiate the changes in therapy indicated by the results, and overall survival remains poor, with a median of 2 months. Criteria for brain biopsy for the diagnosis of focal brain lesions should be redefined to include selected patients for whom a less invasive approach does not yield a definitive diagnosis.

Pharmacokinetics and tissue penetration of vancomycin in patients undergoing prosthetic mammary surgery.

Vancomycin concentrations in periprosthetic breast tissues were evaluated in 24 women undergoing reconstructive surgery after mastectomy for breast cancer. Patients were given a single prophylactic dose of vancomycin (1 g iv) 1-8 h before surgery, and mean capsular and pericapsular tissue concentrations were measured by HPLC. Vancomycin was not detectable in the majority of patients belonging to the 1-3 h post-dose groups, whereas in the 4-8 h post-dose groups, mean capsular and pericapsular concentrations were as follows: at 4 h, 4.0 mg/kg and 5.9 mg/kg; at 6 h, 4.1 mg/kg and 4. 8 mg/kg; at 8 h, 5.9 mg/kg and 11.1 mg/kg, respectively. Vancomycin tissue concentrations thus were equal to or exceeded the breakpoint of 4 mg/L in most samples collected 4-8 h after dosing. In conclusion, our data suggest that appropriate timing of vancomycin prophylaxis should be considered to allow the maintenance of adequate tissue concentrations throughout the surgical procedure.