Infectious Disease (not AIDS)

Infectious Disease (not AIDS)

Tuesday, October 29 5:00-7:30 PM Infectious Disease (not AIDS) MEDIASTINITIS WITHOUT ANTECEDENT CARDIAC SURGERY Roy Thomas Temes, RE Crowell, DW Map...

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Tuesday, October 29 5:00-7:30

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Infectious Disease (not AIDS) MEDIASTINITIS WITHOUT ANTECEDENT CARDIAC SURGERY Roy Thomas Temes, RE Crowell, DW Mapel, F Follis, SB Pett, Jr, JA Wemly. University of New Mexico Albuquerque, NM , USA. Purpose: Review the etiology and results of aggressive transthoracic surgical treatment of mediastinitis from non-cardiac surgical causes. Methods: A retrospective review of mediastinitis from any cause other than cardiac surgery treated at the University of New Mexico, the Albuquerque VA Medical Center, and the Lovelace Medical Center between June 1, 1992 and May 31, 1996. Patients with deep ceJVical infections superior to the thoracic inlet are excluded. Results: There were 8 patie nts. Seven were male, 1 was female. Median age was 60 years (range 31 to 84 years ). The etiology was Boerhaave's syndrome in 3, iatrogenic in 2 (esophageal intubation and neck injections, 1 each), anastomotic leak following esophagectomy in 1, and necrotizing mediastinitis of unknown cause in 2 patients. The median numbe r of operations was 2.5 (range 1-6). The initial operation was through a thoracotomy in 5 patients and a sternotomy in 2 patie nts. Four patients undetwent drainage through the neck; 1 as primary drainage and 3 combined with transthoracic drainage. Median hospitalization was 45 days (range 3 to 95 days). Complications included mechanical ventilation greater than 48 hours in 88% (7/8), 2 or more operations in 63% (5/8), multi system organ failure in 63% (5/8) and other complications in 75% (6/8) . D eath occurred in 25% of patients (218). Conclusions: Mediastinitis from noncardiac etiologies occurs infrequently. It is a~sociated 'vith significant morbidity, however with aggressive transtl10racic drainage 75% of patients survive. Clinical Implications: Aggressive transthoracic drainage of mediastinitis from non-cardiac surgery causes is the treatment of choice and results in high survival rates.

NOSOCOMIAL PNEUMONIA: PROSPECTIVE STUDY Juan A Mazzei, MD; JM Osses, MD; JO Caneva, MD; EA Arguello, MD; CB Nagel, MD; Z Gutfraind, PhD; M Tokumoto, PhD; R Soloaga, PhD.-Instituto de Cardiologfa y Cimgfa Cardiovascular, Fundaci6n Favaloro, Buenos Aires, Argentina. Purpose: The purpose of this study was to establish: l) Prevalence of nosocomial pneumonia; 2) Prevalence in surgical and clinical patients; 3) Risk factors for nosocomial pneumonia; 4) Usefulness of bronchoalveolar lavage (BAL) and protected specimen bmsh (PSB) techniques; 5) Pathogenic flora; 6) Global mortality in patients with pneumonia; 7) Mortality attributed to pneumonia and 8) Predictive factors for mortality. Methods: Bronchoscopic procedures (BAL + PSB) were performed in 684 patients with clinical suspicion of pneumonia and with a stay of 72 hours or more. The presence of pneumonia wa' dell ned by: l) Clinical suspicion of pneumonia with significant bacteriologic concentration from BAL and PSB; 2) Clinical evolution compatible \\~th pneumonia; 3) Absence of other infectious process with or without positive hemocultures. Mortality attributed to pneumonia was defined by: l ) septic shock; 2) Multiple organ system failure; 3) ARDS; 4) Gastrointestinal hemorrhage with IDC; 5) Massive hemoptysis and 6) Barotrauma and pneumothorax. Cutoff for BAL 2: 104 CUF/ml and for PSB 2: 103 CUF/ml. The statistical analysis wa' performed using the CSS program (STATISTICA, USA). Results: l) Prevalence of nosocomial pneumonia: 1.3%; 2) In surgical patients: 3.4%; 3) In clinical patients: 0.44%; Risk factors: renal failure, dialysis, ARDS, nasogastric tube, endotracheal tube and mechanical ventilation; 4) Nosocomial pneumonia was diagnosed in 241 cases; 5) Most common pathogenic flora: gram-negatives (61%), particularly Pseudomonas aemginosa (27%); 6) Global mortality in patients with pneumonia: 43%; 7) Mortality attributed to pneumonia: 43%; 8) Predictive factors for mortality: age and pumlent secretions. Conclusions: Clinical suspicion should not be used alone in the diagnosis of nosocomial pneumonia as sho\\01 in the present study, in which a big proportion of patients with clinical suspicion of pneumonia were not infected. Clinical Implications: BAL and PSB are essential tools in the diagnosis of nosocomial pneumonia.

OF PIPERACILLI:>IfrAZOBACTAM COMPARED TO OTHER ANTIBIOTICS AGAINST 4,356LOWER-RESPIRATORY ISOLATES OF AEROBIC AND FACULTATIVE ANAEROBIC GRAMNEGATIVE BACILLI FROM HOSPITALIZED PATIENTS. George A Pankey. \-10 : RB Chambers, MS - Ochsner Medical Institutions, New Orleans, Louisiana, USA, a nd the U.S. Piperacillinffazobactam In-Vitro Study Group.

ACTI~1TY

Purpose: To detenrrirre the ilr-t:i!m acti,i t)'of ampicillin/sulbactam (NS), aztreonam (AZf), ceftriaxone (CFX), ceflazidime (CAZ). eipronoxacirr (CIP). imipenc m (Il\.fl ), piperacillin!tazobactam (Pff), and tkarcillin/clavulanate (TIC} against n,spiratory pathogens. Method: A nati01mide (:30 states ) 94-centcr in-vitro susceptibil itv study was begun in 1993. Standardized broth microdilution (Baxte r !\Hcroscan Svstem ) and I\ational Committee for Clinical Laboratorv Standard.~ criteria were used to test single. fresh. rouline (:linical isolates from lower-respiratory tract secre tions. in hospitalize d patie nts. Statistical <..'0111parison was rnade with logistic regression. ResuJts: Thf' m<'
Number or isolates tested- ICUfNon-ICU % Susceptible ICU/Non- ICU K.pneu Enterosp. 4981388 347/444 3491546 26127 77ri5 212 72/i4 86/90 68/68 P.aeru

AIS

AZT CFX

CAZ C IP IMI

Prr

TIC

7W85

97/97

90191 90192 93194 100198

86/87

66164 60/63

88190 88190

15/ 17 7fi!RO 8 1/17

80/82

66171 63171

94194

Overaii* 2107/2249 40/40 75178 66/67 78/83 89/88 91192

80184 78/81

*lndudes 466 S. marcescem. 379 E.coli ..'300 Proteus sp, 239 Acinetobacter sp .. 144 K. oxytoca. 140 C itrobacter sp .. and 71 Morganella morganii.

Conclusions: Overall. I M I, CJP, and Pff had significantly more in-f.litro activity than A/S, AZT. CFX, CAZ, and T IC against these 4,356 isolates (ps for E'tnpilic therapy for lowcr-respiratOJy tract infections due to gram-negative bacilli in hospitalized patie nts. Supported by Lederle (Wyeth-Aye rst Laboratories).

COMPARATIVE EFFICACY AND SAFETY OF 5-DAY AZITHROMYCIN AND IO-DAY CIPROFLOXACIN IN THE TREATMENT OF ACUTE EXACERBATIONS OF CHRONIC BRONCHITIS BOHDAN PICHURKO, M.D., T. BRUYA, M.D., M. DEWAN, M .D. , AND COPD STUDY GROUP, Dept. of Medicine, Sinai Hospital, Wayne State University, Detroit, MI; Inte rnal Medicine, Pulmonary Disease & Critical Care, Spokane, W A; Omaha, NE; and multicenter: Purpose: This multicenter, investigator-blinded study compared the efficacy and safety of azithromycin (AZ), to ciprofloxacin (CP), in the treatment of acute exacerbations of chronic bronchitis caused by susceptible bacterial pathogens. Methods: A total of 167 patients were randomized and received treatment orally with either 5 days of AZ (500 mg on day 1, then 250 mg OD for 4 days; n=86) or lO days of CP (500 mg BID; n-81). Treatment groups were comparable in demographic parameters and other baseline characteristics including symftoms severity (e.g., Anthonisen class). Results: 0 the 138 clinically evaluable patients, 91.4% (64!70) of the AZ-treated patients had a favorable clinical response (cure or improvement) at the end of therapy (day 14; this was comparable to the clinical success rate of the CP-treated patients (94.1 %, 64/68). Similarly, no significant difference in clinical success rates was seen at the convalescent visit (day 28) between the patie nts treated with KZ (90.3%, 56/62) and those treated with CP (88.9%, 56/63). Bacteriological response rates for H. influenzae, M. catarrha/is, and S. pnetmwniae were also comparable at both end of therapy and at convalescence for both treatment groups. The two treatme nt groups also had similar safety profiles. For example, one or more treatment-related adverse events were reported for 34.9% (30/86) and 34.6% (28/81) KZ-treated and CP-treated patients, respective ly. These side effects were rated as mild to moderate; none were classified as severe. Conclusions and Implications: These data indicate comparable efficacy of standard regimens of azithromycin and ciprofloxacin in the treatment of acute bacterial exacerbation of COPD. Supported by Pfizer Phannaceutical and Sinai Research Fund.

CHEST I 11 0 I 4 I OCTOBER, 1996 SUPPLEMENT

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Infectious Disease (not AIDS), continued VENTILATOR-ASSOCIATEDPNEUMONIACOMPLICATINGSEVERE COMMUNITY-ACQUIRED PNEUMONIA Richard G Wunderink MD, FCCP; CB Jones RN, BSN; M Cunningham-Campbell RN; KV Leeper, Jr MD, FCCP- Regional Medical Center and Veterans Affairs Medical Center, Memphis, TN, USA

AIRWAY COLONIZATION IN PATIENTS WITH PROLONGED AND DIFFICULT WEANING FROM MECHANICAL VENTILATION Luca Bianchi, E. Clini, M. Vitacca, R. Porta, A. Zonaro*, R. Solfrini*, N. Ambrosino. Salvatore Maugeri Foundation IRCCS, Gussago (Italy), Division of

Patients(pts) \Vith severe community-acquired pneumonia (SCAP) appear to be prone to ventilator-associated pneumonia (VAP). Risk factors for VAP complicating SCAP have not previously been described. Methods: From l/1/93 through 12/31/95, all181 pts admitted to two MICUs \vith SCAP were prospectively followed. 142 pts received mechanical ventilation (MV). In addition to direct comparison a nested case control comparison was done between SCAP pts who developed VAP and those that did not. All control pts were ventilated :!:2 days of cases. A 10 point score based on duration of ventilation, age, risk factors for SCAP, APACHE III score, sex, hospital, and causative organism was used. Control pts matched VAP pts on an average of 7 pts \vith only 2 pts matching as low as 5 pts. Results: 24/142 (16.9%) of ventilated SCAP pts developed VAP. VAP pts were ventilated for an average of 13.5 days (95% CI 10.6-16.5) before the first episode ofVAP compared \vith an average total duration of MV of 8.7 days (7.3-10.2 ) in non-VAP!ts. MV ~ 10 days (OR 12.7), ARDS (OR 3.79), VAMC admission (OR 6.95), an lack of neutropenia (OR 0.10) were associated "vith development of VAP. In the case-control study, Caucasians (OR 5.32), empiric treatment (OR 30.0), lack ofbronchoscopic diagnosis (OR 4.49), and causative organism, with S. aureus CAP (OR 0.24) least likely, were associated \vith development of VAP. Since MV ~10 days appeared to be the greatest risk factor, aseparate analysis of only pts ventilated ~ 10 days was also performed. None of the risk fac:tors , including ARDS and empiric treatment, fou nd in the first tv:o analyses remained significant. No antibiotic regimen was associated \vith VAP in any analysis. VAP complicating SCAP was not associated \vith an increased mortality (33.3% compared with 37.3% for non-VAP pts). Conclusions: We conclude that the major risk factor for development ofVAP as a complication of SCAP is the subsequent duration of mechanical ventilation. While ARDS is more likely to result in MV ~ 10 days, it does not appear to be an independent risk factor. Also, neither causative organism nor antibiotic regimen appeared to play a significant role in subsequent development of VAP.

Purpose: It is well known that airway colonization enhances the risk of developing ventilator associated pneumonia in Intensive Care Unite (ICU) patients. Nm of the study was to acquire more data on the incidence of colonizing pathogens in tracheostomized and/or intubated patients \vith difficult/prolonged

DIAGNOSIS OF ECHINOCOCCUS PULMONUM BY IMMUNOFLUORESCENT TECHNIQUE Miroslav Gavrilovski MD, PhD; G Breskovska MD PhD, Dokic D MD, PhD; L/ Gligorovski MD, PhD; T Caparoska MD , PhD; Z Arsovski MD - Clinic o Pulmology and Allergy, Medical Faculty, Skopje, Republic of Macedonia Purpose: To evaluate the value of the immunofluorescent technique (IT) in the diagnosis of echinococcus pulmonum. Methods: We have used IT to determinate the tissue infection \vith Echinococcus granulosus or Echinococcus multilocularis in 60 patients \vith suspected pulmonary lesions. Results: Positive immunofluoresce nt (IF) te st for echinococcus pulmonum was found in 43 (71.67 %) of the patients. In 17 (28.33 %) patients IF test was negative. From 17 patients \vith a negative IF test \vith further examinations in 14 of them primary lung cancer was discovered. Only 3 patients with negative IF test had echinococcus pulmonum as a surgical finding. Conclusions: IF technique is a useful tool in the diagnosis of echinococcus pulmonum. Also if a hydatic cyst ruptures or leaks fluid, an anaphylactoid reaction associated >vith eosinophilia and increased IgE leve l may suggest the diagnosis. Clinical implications: Positive IF test means a certain diagnosis of echinococcus pulmonum, but negative IF test does not exclude it.

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Pneumology; *Ospeclale Richieclei, Gussago (Italy), Laboratory oj Microbiology

\Veaning.

Methods: From January to- December 1995 a total of 124 bac:terial strains were isolated from bronchial tracheoaspirates, routinely performed in 44 consecutive, tracheostomized (32) and/or intubated (12) patients, (29M, mean age: 66:!:9years) admitted to a Respiratory Intermediate Intensive Care Unit (RIICU), to be weaned from prolonged mechanical ventilation. Mean duration of stay in RIICU was 14:!:2.7 days, whereas mean weaning time was 4.8 :!:2.7 days. Pneumonia (deflned as new infitrates on chest radiograph, raised white blood cell count, pirexia and the production of purulent secretions) was diagnosed in 16 patients (32%). Tracheoaspirates were performed by sterile methods. A cu t-off point of 104 CFU/ml was establish ed as an indicator of pulmonruy infection. Antibiotic susceptibility was assessed using an agar disk diffusion method according to Kirby-Bauer. Results: S. aureus was the most frequently isolated pathogen among gram positive bacteria (46148, 96% ), while Ps. aemginosa (30 isolates, 40%), Ps. putida (13 isolates, 17%) and Enterobacteriaceae (25 isolates, 32.8%) among g ram negative ones (76 isolates). Concerning antibiotic susceptibility pattern , S. a.ureus strains were mostly (42/46, 91 %)methicillin resistant, whereas among Pseudomonas spp. multiresistant strains were frequently isolated. Conclusions: Bac:terial epidemiology and antibiotic susceptibility in RIICU patients may be considered similar to those staying in a classic ICU. Clinical implications: Ps.aemginosa., Enteroactericeae and Methicillin Resistant S. aureus should always be considered as potential colonizing and infec:ting agents, when prescribing empiric antibiotic treatment in such critically ill patients.

LOW DOSE CEFTIUAXONE VS LOW DOSE CEFOTAXIME IN THE TREATMENT OF RESPIRATORY TRACT INFECTION REQUIRING HOSPITALIZATION Charles K. Chan, MD, FCCP; J Dylewski, MD; DG McCormack, MD; J Brunton, MD; J Dubois, MD- Toronto Hospital & Wellesley Hospitaf, Toronto, St. Mary's Hospital, Montreal, Victoria Hospital, London, Centre Universitaire de Sante de L'estrei, Sherbooke, Canada. Objective: To compare the efficacy and safety of ceftriaxone (CRO) 1 1!/day i.v. \vith cefotaxime (CTX) 1 g TID i.v. in hospitalized patients with rower respiratory tract infections. Design: Multicenter, prospective ly randomized, open label, parallel group study. Setting: Secondary-tertiary care hospitals for the duration of treatment. Population studied: Study patients had a diagnosis of acute hospital or community-acquired pneumonia. A total of 64 patients (33 CRO, 31 CTX) were included in the analysis of drug safety and 46 patients (25 CRO, 21 CTX) were included in the efficacy analysis. Results: Clinical cure: 85% CRO and 80% CTX; microbiological cure: 94% CRO and 87% CTX. Mortality rate was 9.4% (1 CRO, 5 CTX), however for all cases cause of death was underlying disease and not infection. Mild diarrhea was the most frequently reported adverse event (3 CRO, 2 CTX). Conclusions: CRO 1 glday i.v. is comparable to CTX 1 fgTID i.v. in the treatment of uncomplicated pneumonia requiring hospitalization, and both drugs were well tolerated.

Abstracts of Original Investigations, CHEST 1996

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Infectious Disease (not AIDS), continued SEASONAL VARIATION IN COMMUNITY-ACQUIRED PNEUMONIA David Lieberman, D. Lieberman and A. Porath-The Pulmonology Unit and the Division of Internal Medicine, the Soroka Medical Center and the Faculty of the Health Sciences, Ben-Gurion University of the Negev, BeerSheva, Israel Purpose: To detern1ine and describe the seasonal frequency of all case of community-acquired pneumonia (CAP) and of its specific etiologic agents. Methods: All 346 adult patients who were admitted to a regional hospital in southern Israel for CAP over a period of one year were included in a prospective study. As part of the study a comprehensive diagnostic work-up was performed to identifY the specific causative agents for CAP. The study findings were analyzed and are presented in terms of the seasonal distribution of the disease. Results: Thirty-four percent of CAP cases occurred in the spring and only 18% in the fall (p=0.036). Respiratory viruses CAP occurred mainly in the winter and spring (p=0.009) while Mycoplasma pneumoniae CAP reached its peak incidence of 41% in the spring compared with 15% during the winter months (p=0.054). No significant seasonal predominance was observed for the other specific aetiological agents of CAP. In 58% of the CAP patients who were hospitalized in the fall we identified a pneumococcal aetiology while this agent was found in only 32% of the cases in the winter. Conclusions: In contrast with popular public opinion, winter with its low temperatures is not the main reason for the development of community-acquired pneumonia. Most of the specific aetiologies for CAP, with the exception of respiratory viruses and M. pneunwniae, have no seasonal predilection. Clinical imflications: The results of our study can aid in the differential diagnosis o the etiological agents of CAP and the initial therapeutic decisions.

INTERLEUKIN-1 AND INTERLEUKIN-6 IN COMMUNITY ACQUIRED PNEUMONIA: BACTEREMIC PNEUMOCOCCAL PNEUMONIA VS MYCOPLASMA PNEUMONIA£ PNEUMONIA David Lieberman, S. Livnat, F. Schlaeffer, A. Porath and R. Levi-The Pulmonology Unit, the Division oflnternal Medicine, and the Laboratory of Infectious Diseases, The Soroka Medical Center and The Faculty of the Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel Purpose: To determine and compare interleukin-1 (IL-l) and interleukin-6 (IL-6) levels in 2 groups of patients with community-acquired pneumonia (CAP) caused by S. pneumoniae (SP) or M. pneumoniae (MP) in the acute and convalescent phases. We assumed that the difference in the clinical manifestations of the disease would be expressed in the cytokine levels. Methods: Twenty patients with bacteremic SP CAP and 20 patients with MP CAP (diagnosed serologically) comprised the SP and MP groups, respectively. All 40 patients survived hospitalization and underwent a follow-up examination one month after discharge. Results: In the acute phase of CAP, IL-6levels were significantly higher in the SP group than in the MP group (p=0.014). In the same phase IL-l levels were higher in the MP group compared to the SP group (p=0.046). In the convalescent phase cytokines were identified in a considerable number of patients in both groups, in part at levels above those of normal controls. The level of IL-l was significantly higher in this phase in the MP group than in the SP group (p=0.03), but there was no significant difference between the groups in IL-6 levels. Conclusions: The levels ofiL-1 and IL-6 were different between patients with SP CAP and MP CAP during the acute phase. In the convalescent phase cytokine levels remained high in CAP patients, but a difference between the patient groups was seen only for IL-l. Further studies are required on this

issue.

Clinical implications: An association may exist between the clinical pictures of CAP caused by different etiological agents and the IL-l and IL-6 levels.

QUANTITATIVE CULTURE OF BRONCHOSCOPIC SPECIMENS: THE IMPACT OF SAMPLE REFRIGERATION Alec Hull., P. Cardinal, B. Toye, B. Garber, B. Pham. Ottawa General Hospital, Ottawa, Ontario, Canada. Purpose: The bronchoscopic diagnosis of pneumonia relies upon quantitative cultures which exceed a predetermined threshold. Occasionally, samples are refrigerated overnight prior to processing. However, cold exposure may affect the viability of microorganisms. The purpose of this study was to determine if overnight refrigeration affects quantitative cultures of bronchoscopic samples for the diagnosis of pneumonia. Methods: Bronchial washings or bronchoalveolar lavage specimens were collected from 62 patients. Each bronchoscopic specimen was divided into 2 equal samples. The first half was cultured quantitatively immediately whereas the second half was refrigerated overnight at 4°C prior to culture. In addition, to control for variations introduced by the processing of specimens, some samples were cultured quantitatively in duplicate. Results: 78 organisms were isolated. The log of the median colony counts of the pooled samples fell from 6.5 without refrigeration to 6.0 with overnight refrigeration (Wilcoxon Rank Sum test, p=0.02). There was no significant difference between the colony counts of the specimens processed in duplicate (p=0.56). The behaviour of the different sets wa' compared using the ratio of the median count (rm) before and after refrigeration. The decreasing counts were most noticeable with yeast (rm=l.65) and Haenwphilus injluenwe (rm=3.09). Streptococci were the most stable (rm=h.O). In 9 of the 72 cases, overnight refrigeration produced a large fall in counts (>10 ). This behaviour was not correlated with any clinical variable such as antibiotic exposure. Conclusions: Overnight refrigeration has a significant impact on the quantitative culture of microorganisms in bronchoscopic specimens. Haenwphilus injluenzae appears to be the most sensitive organism to storage at 4°C. However, any of the respiratory tract pathogens may occasionally display a significant sensitivity to overnight refrigeration. Clinical Implications: These results suggest that overnight refrigeration of bronchoscoric samples may result in inaccurate colony counts and therefore a missed diagnosis o pneumonia.

SEVERE COMMUNITY-ACQUIRED PNEUMONIA (SCAP) IN THE ELDERLY: EPIDEMIOLOGY AND PROGNOSIS Jordi Rello, Rodriguez R, Jubert P, Alvarez B and the Study Group for Severe-Community Acquired Pneumonia. Hospital de Sabadell and Hospital de Alicante. Spain. Objective: To evaluate epidemiology and outcome of SCAP in the elderly. Methods: Ninety-five patients with SCAP over the age of 64 (mean age: 72.5 years) were studied prospectively during a one-year period. Results: The cause of pneumonia was diagnosed in 37 ((38.9 %) cases, and the most common pathogens were Streptococcus pneumoniae (48.6%), Haemophilus injluenzae (10.8%) and other Gram-negative bacilli (16.2 %). The overall death rate was 40 percent. Eighty-three patients required mechanical ventilation and 40 vasoactive drugs. Using logistic regression analysis, the risk of death was higher in patients with rapid radiologic spread (Relative Risk (RR)=6.99, 95% Confidence Interval (95% CI)=L54 to 31.70), presence of shock (RR=6.70, 95% CI=2.13 to 21.02), previous steroid treatment or immunodepression (RR=5.50, 95% CI=0.77-39.10), development of acute renal failure (RR=3.88, 95% CI=L30 to 11.59) and APACHE II on admission above 22 (RR=2.25, 95% Cl=0.73 to 6.95). Conclusions: elderly patients with SCAP present a high mortality, but it is inappropriate to withhold intensive care on account of age. The presence of complications (rapid radiologic spread, development of shock or acute renal failure) and the severity of illness at initial presentation were the major variables affecting outcome. Excepting immunodepression, comorbidities did not seem to influence outcome. Clinical Implications: recommendations of the ATS guidelines on the empiric therapy of patients with SCAP should not be modified in the elderly patient; nevertheless, it should be noted that half of episodes would be avoided by pneumococcal vaccination.

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Infectious Disease (not AIDS), continued OUTCOME OF PATIENTS SEEN BY THE PULMONARY AND CRITICAL CARE DIVISION FOLLOWING BONE MARROW TRANSPLANT (BMT) RD Herscowitz MD; AE O'Donnell MD, FCCP, DIVISION OF PULMONARY AND CRITICAL CARE MEDICINE, GEORGETOWN Ul\IVERSITY, WASHINGTON, D.C. USA PURPOSE: Respiratory failure is the main cause of death in patients undergoing BMT (Bone Marrow Transplant 1994;14S4:S19-28). We report the outcome of BMT patients seen in consultation by the Pulmonary and Critical Care Medicine Division (PCCM ). METHODS: Retrospective chart review of BMT patients seen by PCCM and review of outcome data on all patients admitted to the BMT service betv.reen July 1994 and December 1995. RESULTS: 149 patients were admitted to the BMT service. 53 patients, 30 allogenic (allo) and 23 autologous (auto) transplants, were evaluated by PCCM. Mean age was 45 years (range 21-65) and mean time after transplant was 221 days (range 1-4380, median 60). An infectious process was diagnosed in 25 of 53 patients (mean day 376, fungal - day 122; non fungal-day 650) and a non infectious process was diagnosed in 28 of 53 patients (mean day 69). The overall in-hospital mortality was 68% (26 of 30 allo (87%) and 10 of 23 auto (43%) ). The in-hospital mortality of those \vith an infectious process was 22 of25 patients (88%) and those with a non infectious process had a mortality of 14 of 28 patients (50%). 96 other BMT patients did not have PCCM consultation. Their in-hospital mortality was 11 of 96 (11%). Overall mortality for all patients admitted to the BMT service was 47 of 149 (32%). CONCLUSIONS: There was an increased mortality in patients who had undergone allo BMT, were seen in consultation by PCCM and in those with an infectious process. CLINICAL IMPLICATIONS: Based on this series, BMT patients seen in consultation by the PCCM service have apoor outcome, but they are not representative of the entire BMT population .

COMPLIANCE WITH INH PROPHYLAXIS IN A PREDOMINANTLY IMMIGRANT GROUP Sharmalie Ratnayaka, MD; S. Dhar, MD; K. Padmanabhan, MD; R. Doshi, MD; K. Gupta, MD; Coney Island Hospital, Brooklyn, New York, U.S.A. Purpose: To study compliance with INH prophylaxis in a municipal hospital setting. Method: A retrospective analysis of 500 clinic patients who were started on INH chemoprophylaxis over a five year period was done. The setting was an inner city hospital chest clinic with a predominant immigrant population. Results: The age distribution of the groups was as follows: l-10 (14.5%); ll-20 (21 %), 21-30 (26.5%); 31-40 (26% ); > 41 (12%). Two hundred seventy three were females and 227 were males. Eighty percent of them were foreign born and 20% were born in the U.S. The breakdown was as follows: Asian-30%, Latin American-27%, European/Russian-25%, Haitian-15%, African-2%, Arabic-1 %. Out of a total of500 cases, 410 (82%) completed six months of prophylaxis. The completion rate in the immigrant group was 81% compared with the U.S. born group of patients who had a completion rate of 86%. Of the 90 patients who did not complete therapy, 51 were females and 39 were males. The most common reason for non-completion of therapy was patient non-compliance in 85% (67/90), INH toxicity as manifested by elevated liver function tests (LFT's) in 9% (8/90). The most common side effect observed was elevation of LFT' sin 8/500 patients giving an incidence of 1.6% and rash in 4/500 patients (0.8%) and non-specific G.I. symptoms in 4/500 patients (0.8%). Conclusion: INH prophylaxis appears to be asafe method of preventing reactivation and spread of tuberculosis. Our patient group appears to be very conscientious about taking INH prophylaxis with completion rates similar in both the immigrant as well as U.S. born patients.

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OUTCOME OF BACTEREMIC PNEUMONIA IN ELDERLY Jayesh K. Parikh MD, V.K.Parikh MD , D K . .Patel MD, M.A.Zubair MD, M.S.Karetzky MD. NEWARK BETH ISRAEL MED. CTR. & UMDNJ, NEWARK, NJ 07112. PURPOSE: In United States about 30 million people \\~II reach age over 65 in year 2000. Pneumonia in the hospitalized elderly patients is more likely to be associated with bacteremia and an increased mortality. The purpose of this study was to determine the mortality rate of bacteremic pneumonia in the elderly and to ascertain prognostic indicators. METHODS: In a retrospective study at NBIMC from May 1992 through April1996, 124 patients greater than 65 years of age with bacteremic pneumonia were identified. Pneumonia was determined by the presence of pulmonmy infiltrates on chest roentogram with fever and physical findings of pulmonary disease. The patients' chmts were reviewed for demographics, medical history, microbial etiology, laboratory values, antimicrobial therapy and hospital location in determining their possible significance \\~th resped to survival. RESULTS: 124 patients were identified, 59(47.6%) were male of whom 29 died while 65(52.4%) were female with 33 deaths (p=NS). Overall mortality in this elderly group was 46%(57/124). Higher mortality was associated with malignancy, mean B. P.<70 mm Hg, presence of confusion, pH < 7.30, multilobar involvement, inappropriate antibiotics, mechanical ventilation and ICU admission (p<0.05). According to Step,vise logistic regression malignancy, place of admission (ICU Vs Non-ICU), type (Nosocomial Vs CAP), extent (No of lobes involved ), coagulase negative staphylococcus as organism and inappropriate antibiotics proved to be independent risk factors for increased mmtality. HIV serology(n=4) was associated '~th 100 % mortal ity. CONCLUSION: Elderly patients with bacteremic pneu monia have a high mortality. The timely administration of appropriate antibiotic therapy is a significant independent risk factor associated with survival. This should prompt aggressive attempts to determine the specific causative agent in order to assure the most specific therapy.

PROSPECTIVE STUDY OF COMMUNITY ACQUIRED PNEUMONIA( CAP): DIAGNOSIS ETIOLOGY, RISK FACTORS AND OUTCOME IN HOSPITALIZED PATIENTS Jayesh K. Parikh MD, V.K.Parikh MD, D.K.Patel MD, M.A.Zubair MD, M.S.Karetzky, MD. NEWARK BETH ISRAEL MED. CTR. & UMDNJ, NEWARK, NJ 07ll2. PURPOSE: In the USA approximately 4 million cases of CAP occur annually that demonstrate a grO\ving diversity of causative organisms and significant mortality. The purpose of this study is to evaluate prognostic and comorbid factors influencing mortality and morbidity. METHODS: Patients with CAP admitted from the ER from July 95 to April 96 were prospectively surveyed. CAP was defined as febrile illness or respiratory symptoms with a new infiltrate on chest X-ray. Data included demographics history, ~tal signs,lab values, antibiotics(abx) prescribed and discharge status. The variables were analyzed utilizing SAS. RESULTS: During the study period 223 patients with CAP were identified, 41% male and 92% African American with a mean age of 47.3 years. Premorbid conditions included diabetes (14.3%), malignancy (13%), renal (11.2%), heart (35%), and neurological (9.9%) Diseases. Patients had a high incidence of smoking (60%), alcohol overuse (49%) and IVDA (34%). HIV serology was positive in 35% On presentation, patients had fever (66%), cough (73%), sputum production (55%), chest pain (36%) and dyspnea (62%). They were usually febrile (mean temp. 100.7F) with a mild leucocytosis (mean WBC 11.7/cmm) and hypoxic (mean Pa02 71.5 mm Hg). At least one pathogen was identified in 49% patients: blood (n=33), sputum (n=33), BAL (n=42), serology (n=2l). Mycoplasma pneumonia was the commonest organism identified (16), S. pneumonia (14), pseudomonas (8). PCP (8) and S. aureus (7). The macrolides (25%) were the abx most frequently used next the cephalosporin (22%) or combination (16%) The mean LOS was 10.4 days \~than overall mortality of9.9%, patient \vith AIDS 15.4%, those admitted to the medical floor 8% & ICU 16%. Conclusion: CAP was commonly associated \vith confounding factors especially a (+) HIV serology. Bronchoscopy, blood cultures & serology identified the probable causative agent in 109/223 patients. Mortality was as found in other studies, greater in ICU patients and those \~th AIDS. Abstracts of Original Investigations, CHEST 1996

Tuesday, October 29 5:00-7:30

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Infectious Disease (not AIDS), continued PNEUMOCOCCAL ANTIBODIES IN OLDER TOBACCO SMOKERS INDICATE NATURALLY ACQUIRED IMMUNITY James H. Williams Jr, MD, FCCP; Majid Naderi, MD; Mihn Kim, BS; Ahmad Khawaja, MD; Mark Thomquist, PhD, Gilbert Omenn, MD, PhD; Frank Meyskens, MD - Univ. of California, Irvine, & Univ. of Washington. Purpose: Mortality from pneumococcal infection is increased among older individuals and others with chronic lung disease, and immunization is generally recommended. Tobacco smokers experience frequent respiratory tract infections, but whether this confers a degree of naturally acquired immunity to pneumococcal infections is controversial. We found higher IgG titers for pneumococcal capsular polysaccharides among older smokers, when compared to younger, healthy individuals. We hypothesized these elevated IgG titers among the older smokers would approximate post-immunization IgG titers in the younger group, while IgM titers would not be similarly elevated. Methods: Samples: 1) Baseline blood samples collected older tobacco smokers (age 63::+::3) recruited to a lung cancer prevention trial, who had not previously been immunized. 2) Blood samples collected from younger, healthy individuals (age 38::+::8), collected a) pre- and b) one month post-immunization with 23-valent vaccine. Antibody assays: IgG and IgM titers to the 23 polysaccharides in the vaccine measured in aggregate ELISA, after absorption of samples with cell wall polysaccharide. Results: Both IgG and IgM titers were significantly elevated one month following immunization of the younger, healthy individuals. Higher IgG titers among unimmunized, older smokers approximated post-immunization titers in the younger group. In contrast, baseline IgM titers did not sigruficantly differ between the two groups. Conclusions: The elevated IgG titers demonstrate that older tobacco smokers can acquire durable, natural immunity to pneumococcal infections, presumably due to recurrent airway infections. Clinical Implication: Although antibody responses to immunization have been reported to be blunted in older individuals, naturally-acquired immunity may induce comparable antibody titers regardless. While this might imply lesser benefit of the vaccine in this population, we would instead argue that because these individuals can maintain elevated antibody titers, immunization should be offered to better ensure induction of a degree of natural immunity.

REFINING RAPID DIAGNOSTIC PROCEDURES FOR WHOOPING COUGH:COST OR ACCURACY? N. Cimolai and C. Trombley, Department of Pathology and Laboratory Medicine, B.C.'s Children's Hospital, Vancouver, Canada Purpose: In the pediatric setting, a diagnostic assay with the polymerase chain reaction (PCR) is the current standard for the rapid diagnosis of Borcktella pertussis infection. Although of tremendous benefit, we sought to determine if reductions could be made to the cost of the assay by either shortening the process time or reducing the volume of reagents. Methods: The standard for comparison was the PCR technique essentially as described by Glare eta!. (J Clin Micro 28:1982-1990); all assays were applied to nasopharyngeal washes from children. Clinical samples were proteinase K treated and boiled, and this template was then used for all amplification assays. An amplification product of 153 bp was visually examined after conventional agarose gel electrophoresis and ethidium bromide staining. The experimental components included two phases: a) amplification cocktails were reduced in volume from 100 to 50 ul. while maintaining the same realtive proportion of constituents, and b) while maintaining the 50 ul. volume, thermocycling runs were sigruficantly shortened in order to decrease processing time. All specimens had previously been deemed positive by our standard assay. Results: For the small volume assessment, 7/85 (8.2%) of specimens were negative. Among the latter false negative specimens, 5n were culture negative. For the short cycle/small volume assessment, 11/81 specimens were negative (13.6%), and among these false negatives, 9/11 were culture negative. When positive, the modified protocols yielded appropriate products which were not any less appreciable than those which were obtained by the standard assay. Conclusions: The modified PCR assays have the potential to save on cost and time, but at the expense of a reduction in positive diagnoses. Unfortunately, most of the false negative assays have occurred for patients where culture back-up would not have been of value and where the clinical diagnosis is often problematic. Clinical Implications: In the implementation of any such cost-saving strategy, further study will be required to determine whether the benefits of cost-saving outweigh the detriment of missed diagnosis.

ORAL VACCINATION ADJUVANTS IN AN ANIMAL MODEL OF

MYCOPLASMA PNEVMONIAE INFECTION

N. Cimolai and A.C.H. Cheong, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada Purpose: We have previously shown that peroral immunization with M.

pneurrwnine reduces the histopathology in an animal model after live challenge.

In this work, we sought to determine if adjuvants could boost humoral immunity and effect increased protection. Methods: Golden hamsters were orally immunized with gastric instillation of heat-killed M. pneurrwniae weekly for one month except for controls. Two vaccine adjuvant groups included co-administration of M. pneurrwniae with either cholera toxin B subunit (CTBs) or combined E. coli 055/Shigella lipopolysaccharide (LPS). Two weeks after the final oral vaccine dose, animals were challenged with intratracheal!intranasal inocula and then harvested 10 days later. Sagittal sections of lung were stained with H&E and assessed with a histological scoring method as previously detailed (Micro Immunol 36:401-1992). Results: Despite the small number of animals per group (5), sigruficant differences were observed between control and vaccine groups: control Mp only Mp+CTBs Mp+LPS

so

mean score 11.3 8.2 7.8 9.1

1.23 2.56 2.22 1.33

E 0.02 0.015 <0.005

Sigruficant differences between vaccine groups however were not realized. Ill effects of adjuvant vaccine were not apparent. Secretory IgA anti-P1 adhesin could not be detected in peripheral blood as assessed by immunoblotting prior to live challenge although 115 from each animal group had evidence of circulating IgG anti-Pl. No significant differences were appreciable for either frequency of or time to culture positivity. Conclusions: Oral vaccination for M. pneurrwnine reduces the degree of histopathology after subsequent live challenge but this effect is not enhanced by mucosal adjuvants in these small groups. Clinical Implications: Mucosal immunization for M. pneurrwniae holds promise but further experimental studies for vaccine enhancement will be required.

PASSIVE IMMUNIZATION WITH POLYCLONAL ANTISERA DOES NOT RESULT IN EARLY ACCENTUATED HISTOPAmOLOGICAL RESPONSES AFfER LIVE CHALLENGE IN AN ANIMAL MODEL OF MYCOPlASMA PNEUMONIAE INFECTION N. Cimolai, A. Cheong, G. Taylor, B. Morrison, Departments of Pathology and Laboratory Medicine, and Health Care and Epidemiology, University of British Columbia, Vancouver, Canada. Purpose: In the hamster model of M. pneumoniae infection, rechallenge experiments with live M. pneumoniae result in an early hyperaccentuated histopathological response. We sought to determine whether this accelerated response could be recruited by the humoral arm of immunity. Methods: Three groups of animals were challenged with live M. pneumoniae: 1) control animals, 2) animals which had been previously administered hyperimmune sera from challenge/rechallenge hamsters, and 3) animals which had been previously administered hyperimmune sera from vaccinated rabbits. Uve challenges were accomplished with combined intratracheaVintranasal inocula on the day after passive immunization and animals were sacrificed on days 3 and 10 post-infection. A histopathological scoring scheme (Micro Immunol 36:401-1992) was applied to sagittal sections of each lung which had been stained with H&E after formalin fixation. Samples of lung were cultured with modified Hayllick"s medium. Results: Significant differences in absolute culture positivity or time to culture positivity were not apparent. By immunoblotting, it was determined that rabbit IgG anti-P1 persisted past the day 10 haiVest. Mean histopathofogy scores were:

1) control 2) hamster sera 3) rabbit sera

~ 6.1 6.3 7.9

day 10 7.4 6.4 6.4

Significant differences were not seen either between animals groups or between day 3 and day 10 samplings. Perivascular reactions were not observed. Conclusions: Passive immunization with polyclonal antisera does not result in early hyperaccentuated histopathological responses after infectious challenge. Clinical Implications: Humoral immunity does not recruit harmful pulmonary responses to M. pneumoniae infection and active vaccination may be a viable option as a preventative strategy.

CHEST I 110 I 4 I OCTOBER, 1996 SUPPLEMENT

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Infectious Disease (not AIDS), continued

Interstitial Lung Disease

THALUUM-201 AND GALUUM-67 SCINTIGRAPHY IN THE DIAGNOSIS OF PULMONARY DISORDERS Rnjesh R. Jasani*, S. Patel, MA Zubair, MS Karetzky. Newark Beth Israel Medical Ce nter, UMDNJ, NJ

THE DIAGNOSIS OF LYMPHANGIOLEIOMYOMATOSIS (LAM) AND HISTIOCITOSIS X (Hx) NEED TO BE HISTOLOGICALLY PROVEN? Sergio Harari, M. Barberis*, E. De Juli, F. Colombo0, G. Cimino, L. Sabolla0 and E. Soresi. Pneumological Department and *Institute of Pathology Niguarda Hospital Milan, Italy. 0Villa Marelli Institute for Chest disease Milan, Italy.

Purpose: Gallium-67 scintigraphy (67 Ca) has been used for the diagnosis of a variety of inflammatory lung diseases in the presence of an inconclusive chest xmy (CXR). We have found thallium-201 (201TI ) to have comparable in terstitial uptake for the evaluation of pulmonary parenchymal disease yet offers the advantages of immediate imaging and diagnosis. ... Methods: \Ve prospectively obtained 201TI scans prior to all6 1Ca scans which were indicated to screen for suspected active lund1 disease. The uptake above the soft-tissue background was considered as grade I , heart uptake was used for 2 TI and stemal uptake was used for 67ca as background for grades II , III , and JV. Grade II and above were considered positive for indicating ~i presenct. of an active parenchymal process.

TI and 61 Ga for the diagnosis of pulmonary disease are

Results: Results and overall statastical analysis of

shown in the table.

Tl+l

Diagnosis

No.

Ga-

Pne umonia PCP Sarcoidosis Pulmonary TB Lung Cancer CHF COPD-Asthma Bronchiectasis Sepsis Syndrome ARDS i\tAI Infection Pulm. Embolism LT-Rejection LT-Infection Norma1 Total

79 39 16 13

25

201n 67Ga

TI-

/Ca+

()

0 0 0

4 I 0 2 0

12

Tl+l

Ga+

TI-

fGa-

47 33 II

0

0 0

10 0

0 0

0

0 I

0 0 42 235

53

I

7 0

0 40

119

6Q

Sens.

Spec.

D,A

PPV

NPV

89%

98%

90%

99%

63%

98%

69%

99%

65% 36%

(+)=positive, (-):: negdtive, LT=Post Lung transplantation, Nonnai=No pulmonary disease/Heart failure(CHF ), Sens .=Sensitivity, Spec. =Speciflc ity, DxA=Oiagnostic Accurac_y, PPVINPV=Positive!Negative Predictive Value . Conclusions & Clinica1 Implic_!ltions: The greater sensitivity of 20ln and its several inherent advantages suggest that 201Tl should replace 6J Ga as the radioisotope of choice for diagnosis of pulmonary disease.

ACTIVITY OF AMPICILLIN/SULBACTAM, TICARCILLIN/CLAVULANATE, AND PIPERACILLINII'AZOBACTAM AGAINST 4,659 CLINICAL ISOLATES OF AEROBIC AND FACULTATIVE ANAEROBIC GRAM-NEGATIVE BACILLI FROM INTENSIVE CARE UNIT PATIENTS. George A Pankey. MD; RB Chambers, MS - Ochsner Medical Institutions, New Orleans, Louisiana, USA, and the U.S. Piperacillinffazobactam In-Vitro Study Group. Purpose: To determine the in-citra activity of ampicillin!sulbactam (A/S), ticareillin/clavulanate (T/ C), and the newly-marketed piperacillin/tazobactam (Ptr). Method: A nationwide (32 states ) 96-center in-vitro susceptibility study was begun in 1993. Standardized broth rnicrodilution (Baxte r Microscan System) and National Committee for C linical Laboratmy Standards criteria were used to test single, fresh, routine clinical isolates from individual IC U patients. Statistical comparison was made with logistic regression with toleranc_-e for Type l error set at 0<=0.05. Results: The median number of isolates tested per center was 49. The isolates were obtained from lower-respiratory tract (2,107), urine (1,178), wounds/soft tissue (511). blood (395). intra-abdominal (144 ). and other sites (259).

AIS Pff TIC

AIS Pff TIC

AIS Pff T IC

E.coli (961) 64164 91/16 87132 S.marc (349) 9164 86132 65132 Citro (187) 45164 61'/256 59/256

(Number of isolates tested) % SusoeptibleJMIC 90 P.mira P.aen~ K.pneu (648) (417) (729) 14164 89/16 1'/256 87/64 9612 86/128 8732 95/2 80/128 E.aero P.vulg K.oxyt (288) (52) (145) 59132 621128 37164 61'/128 90116 94/256 86/32 601128 94/2 Overall Acine Enter (221) (72) (4659) 70164 371128 461128 68/256 82/128 531>256 791128 61'1>256 68/256

E.cloa (502) 17/128 651256 551256 M.morg

(88) 11'/64 89132 79/128

Conclusions: The activity of Pff was greater than that of NS against all isolates except Acine w here

Purpose: LAM and Hx are two cystic nodular lung diseases with peribronchial distribution. The rareness of both diseases make difficult the diagnosis to be made in early stages, e venif the clinical ground is typical. In advanced diseases videoassisted thoracoscopic biopsy (VAT) can present some risks. Methods: Therefore we retrospectively evaluated our experience in the diagnosis of the 20 patients (pts) presenting radiological findings of cystic nodular lung disease. Results: Pulmonary function test (PFT) showed an obstructive or mixed pattern while a pure restrictive one was observed only in initial disease cases presenting reticular pattern at high definition computed tomography (HRCT). The clinical radiological suspicion ofHx was made in 13 cases while in 7 LAM was suspected. Diagnosis in Hx pts were made as follow: 3 VAT (2 in pts with > 3% of CD l a positive cells in BAL), l TBB, l fine needle aspiration, 5 BAL (more than 3% of CD l a pos cell and 2 Birbeck granules)_ 3 pts presented bone eosinophilic granuloma, 2 diabete insipidus. Only 4 pts had a clinical-radiological diagnosis, in 1 case confirmed of autopsy. In LAM pts diagnosis was made in 3 cases by TBB, 5 out of 7 pts presented renal angiomyolipoma. 4 clinical radiological-diagnosis were confirmed in 3 cases by the explanted lungs for transplantation. VAT were performed in 2 LAM and 3 Hx: all procedures have been complicated by prolonged aiiway leakages. Conclusions: In our opinion in specialized centers clinical-radiological diagnosis of LAM and Hx may be acceptable.

PULMONARY ENDOCRINE CELLS IN USUAL INTERSTITIAL PNEUMONIA N. Camimeo Ph.D; M.P. Foschino MD; S. Talamo MD; G. Pietrafesa MD; V. Rizzo MD - Dpt. of Internal Medicine and occupational disease- University of Bari; Italy. Purpose: For the lack of data in literature of endocrine cell modifications in Usual Interstitial Pneumonia (UIP), we led a research utilizing methods able to identify pulmonary endocrine cells: morphologic, immunohistochemical and histochemical types. Methods: In three cases of UIP, histologically documented, we tested on tissular sections some antibodies (Vimentin, Smooth Muscle Actine and Desmine). to have a topographical confirmation of the most commonly observed lesions in UIP, i.e. the presence of focuses of fibroblasts and smooth muscular diffuse hyperplasia both of vases and interstitium. Among endocrine markers the following monoclonal and polyclonal antibodies have been tested: bombesin, gastrin, calcitonin, cromogranin, neuronal specific enolase. Results: The markers of fibrosis and smooth muscufar hyperplasia revealed themselves useful. The three cases (characterized by fibrosis from mild to grave level) showed strong positivity for vimentine, desmine and smooth muscle actin, the last two as markes of "fibroblastic focuses". Referring to the presence of endocrine markers, a more intense positivity has been n oticed in the two cases with mild fibrosis; in the case with the lower positivity percentage, the grade of fibrosis is more severe. Conclusions: Our case-report, although limited to three cases of UIP, allows us to point out that the pulmonary endocrine component seems to disappear progressively in relation to the evolution of fibrotic process. Clinical Implications: This method seems to be very useful together \vith other investigation methodologies to screen and monitoring UIP.

it was least active. Pffwas more active than TIC against E. coli, P.aeru, and E.cloa, and equivalent against

the remaining isolates. Overall. the in-vit ro activity of Pff \vas superior to that of both A/S and TIC at p
Supported by Lederle (Wyeth-Ayers! Laboratories).

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Abstracts of Original Investigations, CHEST 1996