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Nosocomial respiratory tract infections in multiple trauma patients. Influence of level of consciousness with implications for therapy.

A prospective study of 161 multiple trauma patients was carried out to determine the incidence, the causative agents, and the outcome of nosocomial respiratory tract infections in this highly selected population. Thirty-eight (23.6 percent) patients developed a nosocomial pneumonia (NP). In addition, there were four superinfections in three patients, representing an incidence of 26 percent (42 of 161). Incidence of NP was significantly greater among comatose patients (42.2 vs 13.3 percent, p less than 0.05). Furthermore, purulent tracheobronchitis was diagnosed in six patients. The causative agent of NP was identified in 36 (85.7 percent) episodes by means of fiberoptic bronchoscopies with protected specimen brush sampling. Staphylococcus aureus (55.8 percent) was the predominant pathogen isolated in multiple trauma patients in coma (Glasgow coma score [GCS] below 9 during a period greater than 24 h), while aerobic Gram-negative bacilli were responsible for the majority of cases in the remaining population studied. The overall mortality rate was 19.8 percent, but only five deaths were related to NP. We conclude that nosocomial respiratory tract infections are a frequent problem in multiple trauma patients, especially in those with GCS below 9, although this complication is associated with a relatively low mortality. Among patients with GCS below 9, S aureus was a frequent finding; consequently, antimicrobial therapy in this population needs to be different than that for the remaining multiple trauma patients with NP.

Risk factors for infection byPseudomonas aeruginosa in patients with ventilator-associated pneumonia

Objectiveto investigate the epidemiology of infection byPseudomonas aeruginosa in patients with ventilator-associated pneumonia (VAP).Designprospective clinical study.Settinga medical-surgical ICU in a university hospital.Patientswe followed-up 568 mechanically ventilated patients and 83 episodes of VAP with etiologic diagnosis in 72 patients were retained for analysis.ResultsPs. aeruginosa was isolated in 22 (26.5%) episodes in 18 patients. Of these episodes 7 were directly responsible for death. Using logistic regression analysis, the risk of VAP due toPs. aeruginosa was increased in patients with chronic obstructive pulmonary disease (relative risk (RR)=29.9, 95% confidence interval (CI)=4.86-184.53), a mechanical ventilation period longer than 8 days (RR=8.1, 95% CI=1.01-65.40) and prior use of antibiotics (RR=5.5, 95% CI=0.88-35.01).Conclusionspatients with VAP and these factors have a greater risk of infection byPs. aeruginosa and empirical therapy for these episodes should include anti-pseudomonal activity until etiologic diagnosis is established.

Widespread Bronchogenic Dissemination Makes DBA/2 Mice More Susceptible than C57BL/6 Mice to Experimental Aerosol Infection with Mycobacterium tuberculosis

ABSTRACT We have used the murine model of aerosol-induced experimental tuberculosis to assess the effects of four clinical isolates and a reference strain of Mycobacterium tuberculosis on resistant C57BL/6 mice and susceptible DBA/2 mice. Histological studies and detection of 25 cytokines potentially involved in the infection were carried out. DBA/2 mice showed higher concentrations of bacilli in bronchoalveolar lavage fluid and lung tissue. Furthermore, these mice evidenced a larger granulomatous infiltration in the parenchyma due to an increased rate of emigration of infected foamy macrophages from the granulomas to the neighboring pulmonary alveolar spaces. The better control of bacillary concentrations and pulmonary infiltration observed in C57BL/6 mice from week 3 postinfection could result from their higher RANTES, ICAM-1, and gamma interferon (IFN-γ) mRNA levels. On the other hand, the higher MIP-2 and MCP-3 mRNA levels seen in DBA/2 mice would result in stronger lung recruitment of macrophages and neutrophils. Additionally, DBA/2 mice showed increased inducible nitric oxide synthase expression, induced by the larger number of foamy macrophages, at weeks 18 and 22. This increment was a consequence of phagocytosed bacillary debris, was independent of IFN-γ expression, and could exert only a bacteriostatic effect. The results of the study suggest that DBA/2 mice are more susceptible than C57BL/6 mice to M. tuberculosis infection due to a higher bronchial dissemination of bacilli inside poorly activated foamy macrophages.

Clinical InvestigationsNosocomial Respiratory Tract Infections in Multiple Trauma Patients: Influence of Level of Consciousness with Implications for Therapy

A prospective study of 161 multiple trauma patients was carried out to determine the incidence, the causative agents, and the outcome of nosocomial respiratory tract infections in this highly selected population. Thirty-eight (23.6 percent) patients developed a nosocomial pneumonia (NP). In addition, there were four superinfections in three patients, representing an incidence of 26 percent (42 of 161). Incidence of NP was significantly greater among comatose patients (42.2 vs 13.3 percent, p less than 0.05). Furthermore, purulent tracheobronchitis was diagnosed in six patients. The causative agent of NP was identified in 36 (85.7 percent) episodes by means of fiberoptic bronchoscopies with protected specimen brush sampling. Staphylococcus aureus (55.8 percent) was the predominant pathogen isolated in multiple trauma patients in coma (Glasgow coma score [GCS] below 9 during a period greater than 24 h), while aerobic Gram-negative bacilli were responsible for the majority of cases in the remaining population studied. The overall mortality rate was 19.8 percent, but only five deaths were related to NP. We conclude that nosocomial respiratory tract infections are a frequent problem in multiple trauma patients, especially in those with GCS below 9, although this complication is associated with a relatively low mortality. Among patients with GCS below 9, S aureus was a frequent finding; consequently, antimicrobial therapy in this population needs to be different than that for the remaining multiple trauma patients with NP.

Elevated serum procalcitonin values correlate with renal scarring in children with urinary tract infection.

Background. Urinary tract infection (UTI) in young children carries the risk of parenchymal damage and sequelae. The location of the infection within the urinary tract influences decisions regarding both therapeutics and follow-up. Because clinical features and laboratory markers of infection at an early age are not specific, it is difficult to make a distinction between lower UTI and acute pyelonephritis. Procalcitonin (PCT) has been studied as a marker of severe bacterial infection. The aim of this study was to test the usefulness of PCT concentration in serum to distinguish between uncomplicated UTI and severe acute pyelonephritis with renal scars. Methods. PCT was measured by immunoluminometric assay in serum samples from children with microbiologically documented infection. Severe renal involvement was assessed by 99mTc-dimercaptosuccinic acid gammagraphy done 5 to 6 months after the episode to check for the presence of parenchymal scars. C-reactive protein (CRP) and leukocyte count were also measured. Results. PCT at presentation showed a significant correlation (P < 0.001) with the presence of renal scars in children with UTI. Using a cutoff of 1 ng/ml for PCT and 20 mg/l for CRP, sensitivity and specificity in distinguishing between urinary tract infection with and without renal damage were 92.3 and 61.9%, respectively, for PCT and 92.3 and 34.4% for CRP. Positive and negative predictive values were 32 and 97.5%, respectively, for PCT and 23 and 95%, respectively, for CRP. Conclusions. A low PCT value at admission indicates a low risk of long term renal scarring. Increased PCT values at admission correlate with the presence of scars. PCT values have proved to be more specific than CRP and leukocyte count for identifying patients who might develop renal damage.

Evaluation of a New Assay in Comparison with Reverse Hybridization and Sequencing Methods for Hepatitis C Virus Genotyping Targeting Both 5′ Noncoding and Nonstructural 5b Genomic Regions

ABSTRACT We report the evaluation of a new real-time PCR assay for hepatitis C virus (HCV) genotyping. The assay design is such that genotype 1 isolates are typed by amplification targeting the nonstructural 5b (NS5b) subgenomic region. Non-genotype 1 isolates are typed by type-specific amplicon detection in the 5′ noncoding region (5′NC) (method 1; HCV genotyping analyte-specific reagent assay). This method was compared with 5′NC reverse hybridization (method 2; InnoLiPA HCV II) and 5′NC sequencing (method 3; Trugene HCV 5′NC). Two hundred ninety-five sera were tested by method 1; 223 of them were also typed by method 2 and 89 by method 3. Sequencing and phylogenetic analysis of an NS5b fragment were used to resolve discrepant results. Suspected multiple-genotype infections were confirmed by PCR cloning and pyrosequencing. Even though a 2% rate of indeterminates was obtained with method 1, concordance at the genotype level with results with methods 2 and 3 was high. Among eight discordant results, five mixed infections were confirmed. Genotype 1 subtyping efficiencies were 100%, 77%, and 74% for methods 1, 2, and 3, respectively; there were 11/101 discordants between methods 1 and 2 (method 1 was predominantly correct) and 2/34 between methods 2 and 3. Regarding genotype 2, subtyping efficiencies were 100%, 45%, and 92% by methods 1, 2, and 3, respectively; NS5b sequencing of discordants (16/17) revealed a putative new subtype within genotype 2 and that most subtype calls were not correct. Although only sequencing-based methods provide the possibility of identifying new variants, the real-time PCR method is rapid, straightforward, and simple to interpret, thus providing a good single-step alternative to more-time-consuming assays.

Utility of a pneumonia severity index in the optimization of the diagnostic and therapeutic effort for community-acquired pneumonia

The objective was to evaluate the utility of the Pneumonia Severity Index (PSI) developed by Fine et al. as a tool to streamline diagnostic and therapeutic effort. Site of care of patients was recommended in accordance with the PSI class: classes I and II underwent treatment at home and classes III, IV, and V were hospitalized. Class I comprised 37 patients; class II had 30, class III had 20, class IV had 31, and class V had 10 patients. 80 patients were admitted into the hospital, 3 of whom required admittance to the intensive care unit, and 48 were managed as outpatients from the emergency room. Overall mortality was 4 patients (3.1%). Of these, 3 belonged to class IV and 1 to class V. The aetiological diagnosis was obtained in 53.9% of the cases (69/128). If classes I to III are analysed together, the percentage of aetiological diagnoses was 47% (41/87), increasing to 68% (28/41) for patients in classes IV and V. In our experience Fines PSI classification, with rationalization and adaptation to the particularities of each centre, is an effective tool for deciding on hospitalization for selecting the most suitable battery of diagnostic tests based on cost-benefit criteria. However, it is inadequate for young patients with hypoxia or pleural effusion. Therefore, although hospitalization of patients with pneumonia should be mainly based on clinical criteria, Fines PSI classification could help physicians in making more rational decisions in this respect.

Catalase-peroxidase activity has no influence on virulence in a murine model of tuberculosis.

The capacity to generate a chronic and persistent infection in the experimental murine model of tuberculosis induced aerogenically by a low-dose inoculum was determined in eight isoniazid-resistant clinical strains of Mycobacterium tuberculosis showing different catalase-peroxidase (C-P) activities. Determination of bacillary concentration in lung and spleen and the percentage of pulmonary parenchyma occupied by granulomas were monitored. Data showed no relation between the lack of C-P activity and the ability to develop a persistent infection, highlighting the potential of C-P negative strains to spread through the community.

IP-10 is an accurate biomarker for the diagnosis of tuberculosis in children

OBJECTIVEnPerformance of IFN-γ assays in children is compromised. Therefore, we investigated the utility of IP-10 for the detection of active tuberculosis (TB) and latent tuberculosis infection (LTBI) diagnosis in children; comparing its positivity with QuantiFERON-TB Gold In-Tube (QFN-G-IT) and T-SPOT.TB.nnnMETHODSnWe studied 230 children from three groups: active TB, screening (healthy children without known exposure to active TB patient screened at school or by their paediatrician) and contact-tracing studies. IFN-γ release was determined by QFN-G-IT and T-SPOT.TB. IP-10 was detected in QFN-G-IT supernatants by ELISA.nnnRESULTSnWhen combining QFN-G-IT and IP-10 assays, positive results improved significantly from 38.3% in QFN-G-IT and 33.9% in IP-10 to 41.3%. Age and type of contact were significant risk factors associated with positive QFN-G-IT and IP-10 results. IP-10 levels after antigen-specific stimulation were significantly higher in comparison to IFN-γ levels. Correlation between the three assays was good (κ = 0.717-0.783).nnnCONCLUSIONSnIP-10 cytokine is expressed in response to TB specific-antigens used in QFN-G-IT. In conclusion, the use of IFN-γ T-cell based assays in combination with an additional IP-10 assay detection could be useful for diagnosing active TB and LTBI in children.

Intragranulomatous necrosis in pulmonary granulomas is not related to resistance against Mycobacterium tuberculosis infection in experimental murine models induced by aerosol

Intragranulomatous necrosis is a primary feature in the natural history of human tuberculosis (TB). Unfortunately, this phenomenon is not usually seen in the experimental TB murine model. Artificial induction of this necrosis in pulmonary granulomas (INPG) may be achieved through aerosol inoculation of lipopolysaccharide (LPS) 3 weeks after Mycobacterium tuberculosis infection. At week 9 post‐infection, the centre of primary granulomas became larger, showing eosinophilic necrosis. Interestingly, INPG induction was related to mice strains C57BL/6 and 129/Sv, but not to BALB/c and DBA/2. Furthermore, the same pattern was obtained with the induction of infection using a clinical M. tuberculosis strain (UTE 0335R) that naturally induces INPG. In all the mice strains tested, the study of pulmonary mRNA expression revealed a tendency to increase or to maintain the expression of RANTES, interferon‐γ, tumour necrosis factor and iNOS, in both LPS‐ and UTE 0335R‐induced INPG, thus suggesting that this response must be necessary but not sufficient for inducing INPG. Our work supports that INPG induction is a local phenomenon unrelated to the resistant (C57BL/6 and BALB/c) or susceptible (129/Sv and DBA/2) background of mice strains against M. tuberculosis infection.