Severe community-acquired pneumonia: assessment of microbial aetiology as mortality factor.

Community-acquired pneumonia (CAP) remains a major cause of mortality. The aetiology of CAP has rarely been identified as a mortality risk factor. A prospective study was conducted to assess the prognostic factors of CAP patients admitted to the intensive care unit (Centre Hospitalier Departmental Felix Guyon, St Denis de la Reunion, France), with a special emphasis on microbial aetiology. All variables assessing severity were collected, with a special emphasis on microbial investigations. Among 112 immunocompetent patients (mean+/-SD age 54.7+/-15.1 yrs), 84% were male. Severity of CAP was demonstrated by mortality rate (43%), shock (48%), simplified acute physiology score (SAPS; 46.4+/-21.6) and mechanical ventilation support (82%). Mean risk factor score was 2.2+/-1.2. Microbiological identification was obtained in 78.6% of cases, with positive blood culture in 33%. Most frequently, microbial agents were Streptococcus pneumoniae and Klebsiella pneumoniae (42% and 22%, respectively). The univariate analysis recorded the usual mortality variables: age, alcohol consumption, SAPS, shock, mechanical ventilation, positive end expiratory pressure level, positive blood culture, multilobar infiltrates on chest radiograph, neutropenia, and acidosis, and found K. pneumoniae (versus S. pneumoniae, and all CAP) as a mortality factor. The multivariate analysis demonstrated that septic shock (relative risk (RR) 141), K. pneumoniae CAP (RR 27), SAPS (RR 10.7) and positive blood culture (RR 2.7) were independent factors related to death. In conclusion, the present study found that the microbial aetiology, Klebsiella pneumoniae, was an independent risk factor for mortality in severe community-acquired pneumonia.

Treatment of gram-positive nosocomial pneumonia. Prospective randomized comparison of quinupristin/dalfopristin versus vancomycin. Nosocomial Pneumonia Group.

Nosocomial pneumonia is a frequent complication in hospitalized patients. Gram-positive pathogens, particularly Staphylococcus aureus, are responsible for the increasing frequency of nosocomial pneumonia. To evaluate the efficacy and safety of intravenous quinupristin/dalfopristin (Synercid) in the treatment of nosocomial pneumonia caused by gram-positive pathogens we conducted a prospective, randomized, open-label, international, multicenter, comparative clinical trial. Two hundred ninety-eight patients with nosocomial pneumonia were enrolled in 74 active centers in five countries: a subgroup of 171 (87 quinupristin/dalfopristin-treated and 84 vancomycin-treated patients) were evaluable for the major efficacy end points. One hundred fifty received 7.5 mg/kg of quinupristin/dalfopristin every 8 h; 148 patients received 1 g of vancomycin every 12 h. Aztreonam at a dose of 2 g every 8 h could be administered in both groups for coverage of gram-negative organisms, and tobramycin was added for coverage against Pseudomonas aeruginosa. The primary efficacy end point was the clinical response between the seventh and the thirteenth day after the end of treatment in clinically evaluable patients with documented causative pathogen(s) at baseline (bacteriologically evaluable population). Therapy was clinically successful (cure or improvement) in 49 (56.3%) of patients receiving quinupristin/dalfopristin and 49 (58.3%) patients receiving vancomycin (difference, -2.0% [95% CI, -16.8% to 12.8%]) in the bacteriologically evaluable population. Equivalent clinical success rates were also observed in the all-treated population (n = 298), and in the bacteriologically evaluable patients intubated in baseline (39/72 [54%] compared with 36/67 [54%]). The by-pathogen bacteriologic response was similar in both treatment groups, with equivalent clinical success rates for Streptococcus pneumoniae, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus. Adverse events (venous and nonvenous) were equally distributed between groups; 15.3% of quinupristin/dalfopristin patients and 9.5% of vancomycin patients discontinued therapy because of an adverse clinical event. In this study quinupristin/dalfopristin was shown to be equivalent to vancomycin in the treatment of nosocomial pneumonia caused by gram-positive pathogens. Quinupristin/dalfopristin merits further evaluation for the treatment of nosocomial pneumonia caused by methicillin-resistant S. aureus.

[Efficacy and tolerability of pristinamycin vs amoxicillin-clavulanic acid combination in the treatment of acute community-acquired pneumonia in hospitalized adults]. / Efficacité et tolérance de la pristinamycin vs l'association amoxicilline-acide clavulanique dans le traitement des pneumopathies aiguës communautaires de l'adulte hospitalisé.

The aim of this double-blind, 2 parallel group, randomized, multicenter study was to compare the efficacy and the safety of pristinamycin (P), 1 g bid, versus amoxicillin-clavulanic acid (AAC), 500 mg q.i.d., for 10-14 days in the treatment of non severe community-acquired pneumonia in hospitalized adults. From December 1992 to July 1994, 180 patients were included: 92 in the group P and 88 in the group AAC. The both groups were similar on demographic, clinical and bacteriological criteria. 96 pathogens of which more than half were pneumococci, were isolated in 79/180 (44%) patients. The primary assessment was the global success rate defined as long-term (D40 +/- 7), clinical, radiological and bacteriological efficacy in the "per protocol" population (75 patients in the group P and 83 in the group AAC). The global success was obtained in 63/75 (84%) patients in the group P and 70/83 (84.3%) patients in the group AAC. At the end of treatment (D14 +/- 3), theses rates were respectively 85.4% and 84.3%. The both treatments were equivalents. Adverse events (mainly gastro-intestinal disorders) were reported by 55/92 (59.8%) patients in the group P and 49/87 (56.2%) patients in the group AAC.

Five-Day Spiramycin vs Seven-Day Penicillin V in the Treatment of Streptococcal Tonsillitis in Children.

Because of the frequency of penicillin allergies in children receiving ß-lactam antibacterial agents, the macrolides are frequently chosen as alternatives in patients with group A ß-haemolytic streptococcal (GABHS) infections. Spiramycin, amacrolide widely used in paediatrics, achieving remarkably high tonsillar tissue concentrations, was evaluated in this study in comparison with penicillin V (Phenoxymethylpenicillin). 298 children aged 1.5 to 14 years with acute tonsillitis and a positive rapid antigen test for GABHS were randomised to receive either a 5-day course of spiramycin 100 000 IU/kg twice daily or a 7-day course of penicillin V 25 000 IU/kg 3 times daily. Clinical and bacteriological assessments were recorded at inclusion (day 1), at the end of the treatment visit (days 8 to 12), and at the follow-up visit (days 25 to 35). GABHS isolated during the study were analysed by total DNA restriction fragment length polymorphism analysis. Of the 237 children with a positive GABHS culture at day 1,210 (88.6%) were evaluable for complete clinical and bacteriological efficacy at the end of treatment. Clinical efficacy was evident in 96.1% (98 of 102) for spiramycin and in 98.1% (106 of 108) for penicillin V. Bacteriological eradication was achieved in 79.4% (81 of 102) for spiramycin and in 89.8% (97 of 108) for penicillin V. Three failures occurred in the spiramycin group. In intent-to-treat analysis, the success rate (clinical cure and bacteriological eradication) for spiramycin was 77.9% (116 of 149) and that for penicillin V was 83.9% (125 of 149). At the follow-up visit, 182 children were evaluable for efficacy. Clinical cure with or without asymptomatic carriage of GABHS was observed in 97.7% (86 of 88) for spiramycin and in 89.4% (89 of 94) for penicillin V. Three relapses and 1 reinfection occurred in the penicillin V group. Adverse events, mainly gastrointestinal, occurred in 10.7% of spiramycin patients versus 12.8% of penicillin V patients. These results show that a 5-day treatment regimen with spiramycin twice daily is effective and well tolerated in GABHS tonsillitis, and is an alternative to penicillin V when necessary in children.

[Community acquired pneumonias in the region of Montpellier. Increase of pneumococci with reduced sensitivity to penicillins]. / Pneumonies communautaires dans la région de Montpellier. Augmentation des pneumocoques de sensibilité diminuée aux pénicillines.

OBJECTIVES: Bacteriological data indicate that there is an increased incidence of Streptococcus pneumoniae strains with an intermediate sensitivity to penicillin. The goals of the present study was i) to investigate the profile of sensitivity of Streptococcus pneumoniae isolated from patients with bacterial pneumonia in the area of Montpellier and ii) to compare this profile with the findings of the national center registry to better appreciate geographical specificity. METHODS: Fifty-six patients with bacterial pneumonia were enrolled into the study. From September 1989 to March 1994, we performed bacterial sampling including blood cultures, protected brushes and bronchoalveolar lavage specimens. We examined the antibiotic sensitivity of the germs which were isolated. All patients were followed using clinical and radiological criteria. RESULTS: A precise bacteriological diagnosis was established in 83.6% of the population. Streptococcus pneumoniae was found in 47.2% of the samples. In 19%, the strains displayed an intermediate sensitivity to penicillin. All patients recovered. CONCLUSION: We found a higher rate of resistance to penicillin in Montpellier than the common rate of the national reference center in France. The location of Montpellier closed to the Spanish border might, at least in part, explain this difference.

Modality treatment in adult stage I-II Hodgkin's disease with large mediastinal masses: study of 30 cases and review of the literature.

From January 1980 to December 1989, 30 untreated patients with supradiaphragmatic Hodgkin's disease (HD) stage IA to IIBE, presenting a mediastinal mass with mediastinal to thoracic ratio (MTR) > or = 0.33, were treated by combined modality therapy. None had staging laparotomy and the range of MTR was 0.33 to 0.60 (mean 0.43). In the entire group. MOPP chemotherapy (2 or 3 cycles) was followed by mantle irradiation of 40-45 Grays over 26 to 30 days and paraaortic-splenic pedicle irradiation of 30 Grays over 19 days. Complete remission (CR) was achieved in 26 of 30 patients (87%). The remaining 4 patients who failed to respond to initial chemotherapy received salvage chemotherapy and/or autologous bone marrow transplantation (ABMT). With a median follow-up time of 72 months (range 11 to 131 months), overall survival and disease free survival (DFS) were 86% and 78% respectively at 10 years. Five relapses were observed after 10 to 63 months of CR. Among five patients (3 relapsing and 2 failing to respond) who received intensive chemotherapy and/or ABMT, complete remission was obtained in 4 (80%). Univariate analysis of different risk factors such as age, systemic symptoms, E-lesions, histological subtype, sex, MTR and response to initial chemotherapy indicated that early response to chemotherapy was the only significant factor influencing overall survival (p < 0.001). Intensive chemotherapy with ABMT is suggested for patients failing to respond to initial chemotherapy or relapsing after combined modality treatment.