Lung ultrasonography in pulmonary tuberculosis: A pilot study on diagnostic accuracy in a high-risk population.

OBJECTIVES: The validity of lung ultrasound (LUS) in the diagnosis of interstitial or focal lung pathologies is well documented, we assessed its accuracy in the diagnosis of pulmonary tuberculosis (PTB). METHODS: Sonographic signs suggestive of PTB and their diagnostic accuracy were evaluated in patients admitted with clinical suspicion of PTB. Consolidations, subpleural nodules, pleural thickenings or irregularities and pleural effusion were assessed. LUS signs significantly associated with PTB in the univariate analysis (p < .05) were entered in a multivariate logistic regression model. RESULTS: PTB was confirmed in 51 out of 102 patients. Multiple consolidations (OR 3.54, 95%CI 1.43-8.78), apical consolidations (OR 9.65, 95%CI 3.02-30.78), superior quadrant consolidations (OR 4.01, 95%CI 1.76-9.14), and subpleural nodules (OR 5.29, 95%CI 2.27-12.33) were significantly associated with PTB diagnosis. Apical consolidation (OR 9.67, 95%CI 2.81-33.25, p 0.003) and subpleural nodules (OR 5.30, 95%CI 2.08-13.52, p 0.005) retained a significant association in a multivariate model, with an overall accuracy of 0.799. CONCLUSIONS: Our data suggest a possible role of LUS in the diagnosis of PTB, a high burden pathological condition for which the delay in diagnosis still represents a critical point in the control of the disease.

De-escalation therapy among bacteraemic patients with community-acquired pneumonia.

There is no evidence supporting the use of de-escalation therapy (DET) among patients with community-acquired pneumonia (CAP). We assessed the outcomes associated with DET among bacteraemic CAP patients. We performed a secondary analysis of the Community-Acquired Pneumonia Organization database, which contains data on 660 bacteraemic patients hospitalized because of CAP in 35 countries (2001-2013). Exclusion criteria were death within 72 h from admission and an inappropriate empirical antibiotic regimen. DET was defined as changing an appropriate empirical broad-spectrum regimen to a narrower-spectrum regimen according to culture results within 7 days from hospital admission. Two study groups were identified: patients whose antibiotic therapy was de-escalated (the DET group), and patients whose antibiotic therapy was not de-escalated (the N-DET group). The primary study outcome was 30-day mortality. Two hundred and sixty-one bacteraemic CAP patients were included. Gram-positive bacteria were responsible for 88.1% of the cases (Streptococcus pneumoniae, 75.9%). Gram-negative bacteria were responsible for for 7.3% of the cases. DET was performed in 165 patients (63.2%). The N-DET group was characterized by a more severe presentation at admission. After adjustment for confounders, DET was not associated with an increased risk of 30-day mortality. DET seems to be safe among bacteraemic patients with CAP. Randomized clinical trials are warranted to further explore these findings.

An outbreak of multidrug-resistant tuberculosis involving HIV-infected patients of two hospitals in Milan, Italy. Italian Multidrug-Resistant Tuberculosis Outbreak Study Group.

OBJECTIVE: To describe an outbreak of multidrug-resistant tuberculosis (MDR-TB), amongst HIV-infected patients, spread from one hospital in Milan to another. DESIGN: Descriptive epidemiological investigation and molecular typing. METHODS: All cases identified by intensive case-finding were described in terms of clinical characteristics, previous nosocomial exposure to an infectious MDR-TB patient, previous stays in other institutional settings where exposure to MDR-TB could have occurred, and restriction fragment length polymorphism (RFLP) pattern. RESULTS: Between October 1991 and July 1995, 116 cases of MDR-TB were identified (85 at hospital A and 31 at hospital B). A single case patient, infected at hospital A, introduced the strain into hospital B. Eighty-two of the 92 strains available for fingerprinting revealed an identical pattern; 10 strains had unique RFLP patterns. Nosocomial exposure to an infectious MDR-TB patient was ascertained for 39 of the 56 patients with the 'outbreak' RFLP strain at hospital A (69.6%) and for 24 of the 26 patients at hospital B (92.3%). The median duration of exposure was 32 days at hospital A and 40 days at hospital B. For eight patients with the outbreak strain, exposure was determined to have probably occurred in other hospitals, in the community or in prison. CONCLUSIONS: This is the largest nosocomial outbreak of MDR-TB reported in Europe. Exposure to MDR-TB cases in other institutions caring for HIV-infected patients probably contributed to the spread of this epidemic. Strict control measures should be immediately adopted in order to prevent the spread of TB amongst HIV-infected patients in institutional settings in Europe.

Nested polymerase chain reaction for Mycobacterium tuberculosis IS6110 sequence on formalin-fixed paraffin-embedded tissues with granulomatous diseases for rapid diagnosis of tuberculosis.

We evaluated the sensitivity and specificity of a nested polymerase chain reaction (PCR) to the Mycobacterium tuberculosis IS6110 sequence on formalin-fixed paraffin-embedded tissue samples from patients with tubercular and other granulomatous lesions. Five groups of patients and samples were studied: (1) 28 samples from HIV-positive patients with tuberculosis, (2) 8 samples from HIV-negative patients with histologically suspected tuberculosis (confirmed by culture in 5 cases), (3) lymph nodes from 5 HIV-positive patients with Mycobacterium avium-intracellulare infection, (4) lymph nodes from 30 patients with sarcoidosis, and (5) specimens from 17 patients with other granulomatous diseases. The DNA was extracted from sections with a total thickness of 60 microm, and PCR amplified an internal fragment of 123 base pairs. All of the cases with M. tuberculosis infection were PCR-positive, although this sensitivity was partially related to the initial concentration of the DNA used for amplification. Two of the group 4 samples also were repeatedly positive, thus reducing the specificity of the method. All of the cases with granulomatous diseases other than sarcoidosis were negative. We propose a simplified and highly sensitive nested PCR for the diagnosis of M. tuberculosis infection on archived material in HIV-positive and HIV-negative patients.

Tuberculosis among immigrants from developing countries in the province of Milan, 1993-1996.

SETTING: The Province of Milan, which has high rates of immigration from developing countries, and the Villa Marelli Institute (VMI), Reference Centre for Tuberculosis Control of Lombardy. OBJECTIVE: To describe epidemiology and clinical patterns of tuberculosis among immigrants from developing countries (IDCs) in the Province from 1993 to 1996. DESIGN: Retrospective analysis of the registries of the Regional Bureau for Public Health and of the VMI concerning immigrant patients with active TB living in the Province. Restriction fragment length polymorphism (RFLP) analysis of the available strains to detect recent transmission among immigrants. RESULTS: IDCs represented 22.8% of all TB cases. The standardised incidence rate was eight times higher in IDCs compared to Italians. Of 596 cases notified in IDCs, 524 (87.9%) had been referred at least once to the VMI. Of these, 77.2% were diagnosed within 5 years of arrival, and 86.6% were brought to medical attention because of symptoms. RFLP fingerprinting demonstrated that the mean period of stay in Italy was significantly higher in clustered than in non clustered patients (61.5 versus 37.3 months). Spread to the native population was episodic. CONCLUSIONS: The incidence of TB is higher among more recent immigrants (i.e., Peruvians). TB cases are largely due to reactivation of infection occurring in the country of origin. Preventive measures for early diagnosis of disease or chemoprophylaxis of dormant infection are not regularly performed, but should be implemented for those immigrants at high risk.

Immunological status in heroin addicts: effects of methadone maintenance treatment.

In opiate addicts specific and unspecific immune responses were examined, before and after methadone treatment. Anomalous immune responses were characterized by compromised cellular immunity (functional deficits of polymorphonuclear leukocytes and T-lymphocytes) in association with efficient production of antibodies. After methadone treatment an elevation of leukocyte functions was noted. The presence of elevated titres of circulating immune complexes observed in all the patients tested could bring about a functional exhaustion of neutrophils. The defects of cellular immunity can be considered important risk factors in the pathogenesis of infectious diseases in addicts.

A case of costochondral abscess due to Corynebacterium minutissimum in an HIV-infected patient.

Corynebacterium minutissimum, known as the causative agent of erythrasma, has recently been reported as a clinically significant pathogen in the immunocompromised host. We report for the first time the possible involvement of a multidrug-resistant C. minutissimum strain in a costochondral abscess occurring in an HIV-infected patient.

Bacterial pneumonia in adult patients with HIV infection.

Patients with HIV infection are at increased risk for community-acquired bacterial pneumonias, due in part to their defects in B-cell function. Streptococcus pneumoniae is the commonest cause of community-acquired pneumonia, with the second most common bacterial agent being Haemophilus influenzae. These two organisms account for about two-thirds of community-acquired bacterial pneumonias. Frequently bacterial pneumonias appear difficult to distinguish from Pneumocystis carinii pneumonia or other opportunistic lung infections, because of their atypical clinical and radiologic presentations. Community-acquired pneumonias may be recurrent but have low fatality rates. In comparison, nosocomial pneumonias occur primarily in patients with AIDS and are usually due to Staphylococcus aureus, Pseudomonas aeruginosa and other aerobic gram-negative bacilli. Nosocomial pneumonias have high fatality rates. S.aureus is an important cause of morbidity and mortality in patients with AIDS and has emerged as a secondary opportunist in lungs of patients with opportunistic diseases. While appropriate laboratory study is being done, empiric antibiotic therapy should be directed against the microorganisms above described.

[Antibiotic therapy in bronchopulmonary infections]. / Aspetti di terapia antibiotica nelle infezioni broncopolmonari.

Because of difficulties in accurately determining an etiologic diagnosis, the ideal treatment for lower respiratory tract infections remains questionable. Suggested regimens are made on the basis of clinical and epidemiological data. However, the single most common pathogen responsible for pneumonia remains Streptococcus pneumoniae. Atypical pneumonia in younger patients is best treated with macrolides. Older patients without debility or immunodepression are best treated with amoxycillin-ampicillin, second generation cephalosporins or cotrimoxazole, on the basis of local susceptibility patterns of microorganisms. In the treatment of acute bacterial bronchitis in chronic bronchial disease, most antimicrobial agents with activity in vitro against Haemophilus influenzae and Streptococcus pneumoniae are clinically efficacious. Among new pathogens, the importance of Chlamydia pneumoniae is variable according to the studies, and Moraxella catarrhalis was considered almost exclusively responsible for purulent exacerbations of chronic bronchitis. Therapy for empiric treatment of nosocomial pneumonia must ensure coverage for aerobic Gram negative bacilli: the most frequently used includes a semisynthetic penicillin plus an aminoglycoside, but monotherapy with newer broad-spectrum antibiotics (imipenem, ceftazidime, ciprofloxacin, timentin, etc.) seems to be equivalent to combination regimens. The lung is the most common target organ for infectious complications in immunocompromised patients but the diagnostic methods employed in the traditional work-up of pneumonia are often of little or no use in this setting. By far the two most useful clues to management of pneumonia in the immunocompromised host are the underlying host defect and the radiographic pattern of the lung infiltrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Mycobacterial infections in AIDS: an overview of epidemiology, clinical manifestations, therapy and prophylaxis.

One of the most frequent complications of AIDS is Mycobacterial infections. The incidence of tuberculosis has dramatically increased in all countries as a result of the HIV epidemic. Lately, it has been found that the natural history of new Mycobacterium tuberculosis infection is accelerated by HIV disease. In a wide number of cases the emergence of Mycobacterium tuberculosis nosocomial outbreaks of drug-sensitive and drug-resistant strains has been reported in HIV infected patients. The inadequate efforts to provide complete therapy to this kind of patient has caused the emergence of multidrug-resistant tuberculosis, that is responsible for the increased mortality rate in AIDS patients. A renewed interest in mycobacterial infections has also been kindled by the occurrence of Mycobacterium avium infections in patients with acquired immunodeficiency syndrome. The role of Mycobacterium avium as a pathogen is actually confusing and controversial for clinicians who care for AIDS patients. Disseminated Mycobacterium avium infections occur in a high population of HIV infected patients with low CD4+ cell count. Recent studies reported that rifabutin significantly reduced the incidence of Mycobacterium avium bacteremia, although, new macrolides such as clarithromycin and azithromycin are also effective in the treatment of the infection. Therefore, because of the emergence of macrolides resistance, the use of combination therapy is highly recommended in the Mycobacterium avium infection management.

A new predictive model for an improved respiratory isolation strategy in HIV-infected patients with PTB.

SETTING: Luigi Sacco Hospital, Milan, Italy, 1 January 2000-31 December 2010. OBJECTIVES: To develop a predictive score for identifying human immunodeficiency virus (HIV) infected patients with pulmonary tuberculosis (PTB). DESIGN: Retrospective study based on the medical charts of HIV-infected patients admitted consecutively on presumption of PTB. Patients with culture-positive TB were included in the TB group. Culture-negative subjects formed the non-TB group. Risk factors for PTB were identified and a predictive model was developed. The diagnostic test accuracy of the derived score and that of previously developed scores were analysed. RESULTS: A total of 65 patients were included in the TB group and 505 subjects in the non-TB group. An eight-variable model (age, origin, alcohol use, respiratory rate, weight loss, haemoglobin, white blood cell count, typical chest X-ray) was derived. When compared with the different scores, this model showed the greatest area under the receiver operating characteristic curve (0.880). This score was the only one to present a negative likelihood ratio of <0.2, which is the threshold for giving strong diagnostic evidence against TB. CONCLUSIONS: This model may be useful in predicting PTB in HIV patients in low-endemic countries. A validation study is necessary.

Genotyping analyses of tuberculosis transmission among immigrant residents in Italy.

We used DNA fingerprinting to analyse tuberculosis (TB) epidemiology in immigrant patients living in two major northern Italian urban areas. The study population included 1999 TB patients (1500 Italian-born and 499 immigrants). Univariate and multivariate logistic regression models were used to identify risk factors related to clustering similar proportions of immigrant and Italian-born patients (46%) had infection with TB strains that belonged to genetic clusters. This supports the hypothesis that the disease in foreign patients is more likely to have arisen from reactivation of latent infection acquired in the country of origin than from recent transmission. Gender, age, human immunodeficiency virus infection and drug resistance were not significantly linked to TB clustering. Risk factors associated with strain clustering were country of origin (Somalia, adjusted OR (AOR) 3.19, p 0.017; Peru, AOR 2.86, p 0.014; and Senegal, AOR 2.60, p 0.045) and city of residence. Immigrant status in the larger urban area was an independent risk factor for infection with clustered TB, as reinforced by a subanalysis of the Senegalese group. In conclusion, variations in TB transmission were observed among immigrants from different countries and even within national groups, where living conditions have been found to exert a profound impact. These results emphasize the importance of improving social integration of immigrant subjects in order to limit risks of TB transmission in developed countries.

Impact on rates and time to first central vascular-associated bloodstream infection when switching from open to closed intravenous infusion containers in a hospital setting.

An open-label, prospective cohort, active healthcare-associated infection surveillance sequential study was conducted in four Italian intensive-care units. The aim was to determine the effect of switching from open (glass) to closed fully collapsible plastic intravenous (i.v.) infusion containers (Viaflo) on rate and time to onset of central venous catheter-associated bloodstream infections (CVC-BSI). A total of 1173 adult patients were enrolled. The CVC-BSI rate during the open container period was significantly higher than during the closed container period (8.2 vs. 3.5 BSI/1000 CVC days, relative risk 0.43, 95% confidence interval 0.22-0.84, P=0.01). The probability of developing a CVC-BSI was assessed over time comparing open and closed i.v. infusion containers. In the closed container period, it remained fairly constant (0.8% at days 1-3 to 1.4% at days 7-9) whereas during the open container period it increased (2% at days 1-3 to 5.8% at days 7-9). Overall, the chance of acquiring a CVC-BSI significantly decreased by 61% in the closed container period (Cox proportional hazard ratio 0.39, P=0.004).

Interferon-gamma and granulocyte-macrophage colony stimulating factor therapy in three patients with pulmonary aspergillosis.

An immune response mediated by type 2 cytokines is thought to contribute to the development and unfavorable outcome of aspergillosis. Adjuvant therapy with interferon-gamma (IFN-gamma) and granulocyte-macrophage colony stimulating factor (GM-CSF) was added to antifungal treatment in three nonneutropenic patients (one HIV-positive and two HIV-negative patients) with culture proven aspergillosis refractory to classical antifungal therapy. Clinical improvement was observed concomitantly with an increase in peripheral blood leukocyte proliferation and type 1 cytokines production. Our findings suggest an association between the improvement in type 1 cytokine production observed during IFN-gamma and GM-CSF administration and a better control of Aspergillus infection in patients with progressive disease despite adequate antifungal therapy.

Nosocomial bacterial pneumonia in HIV-infected patients: risk factors for adverse outcome and implications for rational empiric antibiotic therapy.

BACKGROUND: Nosocomial bacterial pneumonia (NBP) was once considered a common cause of morbidity and mortality among advanced AIDS patients. However, clinical and microbiological characteristics and outcome-associated risk factors in this population are poorly defined. PATIENTS: We conducted a retrospective study of all HIV-infected patients admitted during the period 1988-2002 at the Infectious Diseases Clinic of Milan, Italy, to determine incidence rate and factors affecting mortality of NBP, and to gather clinical and microbiological findings about the condition. RESULTS: We identified 120 episodes of NBP among 4,967 admissions of HIV-infected individuals. A reduction of incidence became evident after the introduction of highly active antiretroviral therapy (HAART). The more common causative agents were Pseudomonas aeruginosa (33%) Staphylococcus aureus (25%) and Streptococcus pneumoniae (21%). Methicillin resistance was frequent among staphylococci (65%). The mortality rate of NBP was 25.8%. Non-statistically significant factors associated with shorter survival were: CD4(+) count < 10 cells/microl, concomitant lung neoplasm, and complicated roentgenographic picture. Only one factor was significantly associated with lower survival, both in univariate and multivariate analysis: a methicillin-resistant Staphylococcus serving as an etiologic agent of pneumonia (RR 4.05; 95% CI, 1.076-15.239; p = 0.039). CONCLUSION: A decline in incidence of NBP in HIV-infected individuals was observed after introduction of HAART. S. aureus and P. aeruginosa were the leading causes of NBP, but frequency of pneumococcal pneumonia was significant. The sole predictor for mortality was methicillin-resistant Staphylococcus as a pneumonia-causing agent.