HIV: Infection Identification and Therapy

Monday, October 30 HIV: Infection Identification and Therapy 3:50 pm

2:30 pm -

FLUCONAZOLE VS ITRACONAZOLE-FLUCYTOSINE ASSOCIA TION IN THE TREATMENT OF ESOPHAGEAL CANDIDIASIS A DOUBLE-BLIND, PLACEBO-CONTROLLE

t~~~~ATIENTS:

G.Barbaro.MD.FCCP1 G.Di Lorenzo,MD

Department ofEmergency Medlcme,Umversity ofRome "Lll Sapimr.a", Ita INTRODUCfiON. Candidiasis is the most frequent myocolic opportunistic infection in HIV-posi live patients (mean incidence: IS-20"A.).Contrasling opinions exist about the pharmacological treat mont of esophageal candidiasis in HIV-positive patients.Aim of this study has been to value the rot and the therapeutic efficacy of fluconazole (F) and itraconazole (l)-flucytosine (FCT) associatio compared_ with placebe (P), in the treatment of endoscopieally-diagnosed esophageal candidiasis · AIDS patients.METHODS. The study has considered 85 HIV-positive patients (53 males and 3 females,mean age 28±3) at fust episode of esophageal candidiasis diagnosed by endoscopy (grad I-II ofKdosi's endoscopic classification and grades I-II of Barbaro's clinical classification). No oth opportunistic infection of the eaophagns was detected. The patients selected for the study did n follow therapy with AZT and/or with any other antiretroviral drug; in these patients, the mean vatu monoclonal antibodi CD4;, checked by indirect f.!mun~uorescence,using of T cell_s sub~ · (Ortho Diagnostics, Raritan,NJ), was 63±15/mm .The patients have been double-bhndly ran in 3 groups of patients in relation to pharmacological therapy:a)- the patients of 1st group (n=JO )- the patients of 2nd grou received F(J mg!Kgldaily per os) and P (ISO r os); c)-the patients ofJ per os) and F (n=JO) received"! (3 mg!K per os). In order to eva! ily per os) and P (ISO group (n=2S) received P (3 clinical examination was performed every week up to th the efficacy of pharmacologtc end of follow-up (4 weeks); endoscopic examination was performed at the end ofpharmacologi treatment (2 weeks).AII the patients selcled for the study provided informed consent RESULTS. ter 2 weeks oftreatment,complete remimission of endoscopic lesions was observed in 20 patients o F+Pgroup and in 21 patients of I+FCTgroup (p=n.s.); partial remission of endoscopic lesions w observed in 10 patients of F+P group and in 8 patients ofl+P group (p--n.s.), whereas S patients P+P group presented partial remission of esophageal lesions. No response was observed in I patie od l+FCT group and in 20 patients of P+P group, with a difference statistically significant i symptomatology, compl com_p"!ison with F+P an~ l+FCT groups (p
TRIMI!THOPRiliOll CORTICOSTEROIDS OF EFFECT SULFAIIE'l'IIOXAZOLE ( TIIP-SMZ) IliDUCED SIDE EFFI!C'l'S Ill Till! 'l'RI!ATKI!IIT OF PCP.

Rahman H, Knez P, Gorla M, Klapholz A, Talavera Cabrini Medical Center, New York, New York

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is the most effective anti-PCP treatment available today and corticosteroids have a recognized role as adjuvant therapy in severe PCP. Frequent side effects lead to premature discontinuation of TMP-SMZ and use of more toxic and/or second-line We attempted to determine whether steroids agents. decrease the incidence and severity of side effects of TMP-SMZ and allow more complete course of treatment. study included 90 non selected HIV-positive ~:The patients with documented PCP. Medical records were reviewed with reqard to dosage, duration and side effects of treatment. All patients were treated with TMP-SMZ. was discontinued because of side effects ~:TMP-SMZ in 9 out of 61 patients in the steroid group ( 15%) • In the non steroid group, TMP-SMZ was discontinued for side effects in 12 out of 29 patients (42t, P=0.0052). The side effects leading to discontinuation of therapy were fever (6.5% in the steroid group, 21% in the non steroid group, P=0.0461), nausea and vomiting (1.6% in the steroid group, 7.0% in the non steroid group, P=O.l941), rash {3.2% in the steroid group, 17.5%" in the non steroid group, P=0.0148), pruritus (4.9t in the steroid group, 21% in the non steroid group, P=0.0197}. In addition to that, only 19% of the patients in the steroid group developed leukopenia (WBC < J,OOO/mm3 ) , as opposed to 31% in the non steroid group ( P=O. 233). conclusion: In our study the use of steroids significantly decreased the incidence of major side effects that lead to discontinuation of TMP-SMZ and allowed al•ost complete course of anti-PCP therapy. steroids may be useful in all patients treated with TMP-SMZ. Introduction:TMP-SMZ

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DETERMINATION OF gag DNA AND RNA LEVELS IN BKONCHOALVEOLAll LAVAGE CELLS OBTAINED FROM HEALlHY, ASYMPTOMATIC IUV-1 INFECTED INDMDUALS. Angela M. DIMango, MD, L Rogers, MD, 6: P.F. Simonelli, MD, PhD,. FCCP (1). College of PbyaidiDI 6: SU1Jeona, Deputment of Medicine, Columbia University, New York, New York 10032. We previously used phylogenetic analysis of proviraiiUV-1 DNA sequences to demONtrate that viral strains present in the lungs and blood of the same individuals evolve Independently and at cliHerent rates from a presumed common ancestralspedel (Proc. Nat. Acad. ScL USA 91:11378, 1994). To test whether there is a corresponding change in viral burden in the lung with respect to disease progression, we used PCR to quantify levels ofiUV-1gagDNA and RNA in cells obtained by broncboalveolar lavage and from the blood of 11 healthy, IUV-1lnfected Individuals (median CD4 lymphocyte count 338/uL, range 1G-720). The levels of gag DNA in the lavage cells of these asymptomatic individuals were significantly leu than those measured in either their paired blood mononuclear cell fractions, or lavage cells from a group of patients with symptomatic puimcmary disease. In contrast,. similar levels of gag DNA were found in the lavage and bloocl cells from the symptomatic group. gag RNA was detected in the samples from most of the asymptomatic patients. However, the level of gag RNA expreuion was not proportional to gag DNA content, and was only variably detected among the symptomatic group, suuesting that viral replication was differentially regulated in these patients. These results indicate that IUV-1 proviral content Is significantly lower in asymptomatic individuals compared with those with pulmonary disease, and support the possibUity that viral burden in the lung increases in relation to disease progression. (1) Parker B. Francis Fellow in Pulmonary Research. Supported by theW. J. Matheson Foundatloa.

PNEUMOCYSTIS CARINII INDUCES VITRONECTIN RELEASE

FROM CULTURED ALVEOLAR MACROPHAGES Shahzad Ahmad and A.H. Limper. Thoracic Diseases Research Unit, Mayo Oinic and Foundation, Rochester, MN 55905

Introduction: Pneumocystis carinii (PC) pneumonia remains a major opportunistic infection in immunocompromised hosts. Vitronectin (VN}, a 75 -kD glycoprotein present in serum and in the alveolar space interacts with cells in a variety of processes including cell attachment, migration, and proliferation. Our laboratory has previously demonstrated that VN binds to PC and enhances interaction with lung epithelial cells and macrophages (Infect. Immun. 1993. 61: 4302, J. Immunol. 1994. 152: 4549). To further investigate the role of local VN production ~: in host defense against PC, we investigated macrophage release of VN in response to graded PC challange. Normal rats were lavaged to obtain alveolar macrophages (AM), which were then incubated for 12 hrs. with freshly-isolated PC in varying ratios. (PC:AM ranging from 0:1 to 10:1) Culture supernatants were separated by 7.5% polyacrylamide gel, transferred onto nitrocellulose and immuno-blotted with polyclonal rabbit anti-rat VN antibody. Results: We found that increasing concentrations of PC resulted in enhanced VN elaboration by AM in proportional manner. A PC:AM ratio of 10:1 induced a 446±59% increase in VN release from the macrophages (P
Monday, October 30 RAPID DETECTION OF MYCOBACTERIUM TUBERCULOSIS IN CLINICAL SPECIMENS FROM HIV SEROPOSITIVE PATIENTS BY DNA AMPLIFICATION. Andrea GORI, F. FRANZETTI, M. CORBELLING, M. DEGL' INNOCENTI, A. GRASSINI, S. ANTINORI and M. MORONI. Infectious Diseases Clinic, "L. Sacco" Hospital, University of Milan, Milan, Italy. Several recently developed polymerase. chain reaction (PCR) methods forM. tuberculosis have been shown to increase the level of detection of tuberculosis (TB). We evaluate the ability of a nested PCR assay to detect M. tuberculosis directly in clinical specimens, employing two sets of primers that amplified a 394 and a 223 bp fragment respectively, of the mpt 40 genomic fragment. Amplification was performed by using a simple lysis procedure avoiding phenol-chloroform DNA estraction. The sensitivity of detection of M. Tuberculosis by PCR was determined by comparing the cultures and DNA PCRs on a total of 75 clinical specimens (62 sputum,8bronchoalveolar lavages and 5 CSF specimens). Of the 75 specimens assayed 41 were culture-negative for M. tuberculosis as well as PCR-negative. All 26 respiratory samples found positive by culturing in Lowenstein-Jensen medium were also found positive by PCR. In contrast, 3 respiratory samples which had resulted negative in culture were found positive when analized by the nested PCR technique. PCR and cultures were negative in 4 CSF specimens; PCR was positive for one CSF culture-negative sample, collected from a patient with documented TB in other sites. No amplification was observed from any of 9 different non-tuberculous mycobacterial strains tested. In conclusion, we propose nested PCR amplification of the genomic fragment mpt 40 as a specific, rapid and sensitive test for the diagnosis of infection with M. tuberculosis.

IMPACT OF A RESPIRATORY CARE UNIT ON OUTCOMES OF CHRONICVENTILATOR-DEPENDENTPATIENTSIN AN ACUTE CARE HOSPITAL Rachel Lapointe, LPN, S.E. Reinert, MS, N.S. Hill, MD, Departments of Nursing, Information Technology Services and Pulmonary Division, Rhode Island Hospital, Providence, Rhode Island, USA Recent studies have shown highly favorable weaning and survival rates among chronic ventilator-dependent (CVD) patients (pts) treated in a specialized respiratory care unit (RCU). However, such favorable findings may be related to the selection of pts with favorable prognoses as opposed to improved delivery of care. To address this issue, we retrospectively reviewed charts of all pts over 18 yrs who were ventilator-dependent for > 21d in 1986 (1 yr before RCU opened) and 1989 (1 yr after RCU opened). We hypothesized that if selection was an important determinant, pts in the RCU would have better outcomes than those not admitted, but overall outcomes between the years would be similar. Among 111 pts (53 female) for 1986 and 95 pts (38 female) for 1989 (38 admitted to the RCU), outcomes were as follows: Age(yrs) % Weaned LOS(days) %Died %Home 17 58 111 ± 16 41 62 1986 34* 37* 130 ± 20* 55* 58 1989 RCU 7 60 75 ± 8 37 63 non-RCU 18 51 97 ± 10 44 All1989 pts 60 *p < 0.05 RCU vs non-RCU The shorter length of stay (LOS) of non-RCU pts was related to more early deaths in this group. We conclude that pts admitted to an RCU have improved weaning, mortality and home placement outcomes relative to non-RCU pts, and that improvement relates strongly to selection of pts for RCU. Although RCUs could still enhance outcomes of selected CVD pts, improved outcomes are not apparent among all CVD pts after opening an RCU.

Pushing the Pressure Volume Curve: New Concepts in Mechanical Ventilation 2:30 pm - 3:50 pm EFFECTS OF INSPIRATORY FLOW ON RESPIRATORY RATE IN SLEEPING NORMALS DURING MECHANICAL VENTILATION

Alfred M Habel, PM Simon, RW Stroetz, RD Hubmayr, Pulmonary Research Unit, Mayo Clinic & Foundation, Rochester, MN, USA Inspiratory flow is frequently manipulated to enhance patient-ventilator synchrony. We exatnined the effect of inspiratory flow setting on the rate of breathing in 4 normal volunteers during mechanical ventilation (MV). Measurements were made under isocapnic conditions during NREM sleep to assess respiratory rate responses unconditioned by conscious respiratory sensations. Inspired gas was delivered through a nasal mask with a constant flow of either 25 L!min (low flow) or 45 L/min (high flow). Tidal volume was set to 130% of unassisted ·breathing. In the assist/control mode, machine rate (JM) was set to 2 breaths/min (bpm) and trigger rate (jT) was measured at both flow rates. Thereafter, machine trigger mechanisms were disabled and fM was decreased 1-2 bpm every 3 min relative tofT. Inspiratory effort rate (js) was measured from diaphragm and parasternal EMG recordings. With trigger mechanisms enabled, spontaneous respiratory rate increased from 14.8 ± 1.0 bpm at low flow to 17.0 ± 1.4 bpm at high flow (p<0.05). With trigger mechanisms disabled, inspiratory efforts decreased from 14.8 ± 1.0 bpm to 12.0 ± 1.2 bpm at low flow and from 17.0 ± 1.4 bpm to 14.1 ± 1.2 bpm at high flow. The mean change in fs relative tofT (at a given flow) was not different comparing low and high flows (2.75 ± 0.5 vs 2.88 ± 0.70, p=0.57). This data suggest that higher inspiratory flow increases the rate response of the respiratory oscillator during MV. However, it does not affect the ability of the respiratory oscillator to slow its rate in response to lowering machine frequency. This flow effect on rate is not behaviorally mediated. Supported by grants from the Mayo Foundation and the NIH (RR-00585).

HIGH-FREQUENCY OSCILLATORY VENTILATION COMPARED TO PRESSURE CONTROL: ALVEOLAR PRESSURES, LUNG VOLUME, AND ALVEOLAR CELL COUNT. Juan Gutierrez, K. Toro, R. Vinson, M. Jaramillo, L. Margraf, G. Arteaga, D. Black, P. Walters, L. Toro-Figueroa. University of Teus Southwestern Medieal Center, Dallas, Tens.

Introdudion: High-frequency oscillatory ventilation (HFOV) intends to maintain the lungs expanded with a high mean airway pressure, while limiting the peak airway pressure. Similar end points could be obtained with 'pressure control" and positive end expiratory pressure (PEEP). We compared HFOV and pressure control in terms of lung volume, alveolar pressure, hemodynamics, and alveolar cell count in an ARDS model. Methods: 8 swine, weight 9-33 Kg, received 0.09 mi!Kg of oleic acid. An occlusion valve with a side port was connected to the cuffed endotracheal tube. The occlusion pressure (P...) was used as an estimate of alveolar pressure. Respiratory system compliance (C,) was measured with the multiple interrupter technique and functional residual capacity (FRC) with the nitrogen washout technique. Four animals were ventilated with HFOV and 4 with pressure control. The airway pressure
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