Incidence Of Pneumocystis Carinii Pneumonia Research Articles

Cost-effectiveness of prophylaxis against Pneumocystis carinii pneumonia in patients with Wegner's granulomatosis undergoing immunosuppressive therapy.

To assess the incremental cost-effectiveness of 3 Pneumocystis carinii pneumonia (PCP) prophylaxis strategies in patients with Wegener's granulomatosis (WG) receiving immunosuppressive therapies: 1) no prophylaxis; 2) trimethoprim/sulfamethoxazole (TMP/SMX) 160 mg/800 mg 3 times a week, which is discontinued if patients experience an adverse drug reaction (ADR); and 3) TMP/SMX 160 mg/800 mg 3 times a week, which is replaced by monthly aerosolized pentamidine (300 mg) if patients experience an ADR. A Markov state-transition model was developed to follow a hypothetical cohort of WG patients over their lifetimes starting from the time of initial exposure to the immunosuppressive therapy. The effect of PCP prophylaxis on life expectancy, quality-adjusted life expectancy, average discounted lifetime cost (ADLC), and incremental cost-effectiveness was estimated based on data obtained from a literature review. Direct medical costs were examined from a societal perspective, and costs and benefits were discounted at 3% annually. No prophylaxis resulted in a life expectancy of 13.36 quality-adjusted life years (QALY) at an ADLC of $4,538. In comparison, prophylaxis with TMP/ SMX alone increased the QALY to 13.54 and was cost saving, with an ADLC of $3,304. The addition of pentamidine in patients who had an ADR to TMP/SMX resulted in 13.61 QALY, with an ADLC of $7,428. Compared with TMP/SMX alone, TMP/SMX followed by pentamidine increased the QALY by 0.07 at an incremental cost of $58,037 per QALY. Both TMP/SMX alone and TMP/SMX followed by pentamidine prophylaxis strategies dominated the no prophylaxis strategy until the incidence of PCP fell below 0.2% and 2.25%, respectively. Institution of pentamidine therapy for patients with a TMP/SMX ADR increased quality-adjusted life expectancy compared with that with TMP/ SMX alone until the incidence of PCP rose above 7.5%. Prophylaxis using TMP/SMX alone increased life expectancy and reduced cost for patients with WG receiving immunosuppressive therapy. Replacing TMP/SMX with monthly aerosolized pentamidine in cases of ADR further increased life expectancy, although at an increased cost.

Pneumocystis carinii pneumonia in South African children infected with human immunodeficiency virus.

Pneumocystis carinii pneumonia (PCP) has been regarded as uncommon in HIV-infected patients in Africa, but diagnostic difficulties and geographic variability may partly account for this. There is little information on the incidence of PCP in HIV-infected children in Africa. To investigate (1) the incidence and associated features of PCP in African HIV-infected children and (2) the usefulness of sputum induction and nasopharyngeal aspirates (NPAs) for diagnosis of PCP. HIV-infected children hospitalized with pneumonia were prospectively enrolled in a 1-year study in South Africa. History, examination, chest radiology and blood tests (including HIV testing) were performed. Sputum induction (5% NaCl nebulization) or nondirected bronchoalveolar lavage in intubated patients was performed for P. carinii identification using immunofluorescence and silver stain; immunofluorescence was also done on nasopharyngeal aspirates (NPAs). Of 151 HIV-infected children [47% female; median age, 9 (range, 3 to 23) months], 87 had been previously diagnosed with HIV whereas 64 (42.4%) were found to be HIV-positive at the time of admission. PCP occurred in 15 children (9.9%; 95% confidence interval, 5.9 to 15.5) and was the AIDS-defining infection in 13 of 64 (20.3%; 95% confidence interval, 11.8 to 31.5). Only 1 of 59 children receiving prophylaxis (1.7%) developed PCP compared with 14 of 92 (15.2%) not taking prophylaxis [relative risk, 0.11 (0.02 to 0.82), P = 0.007]. PCP-infected children were younger [3 (range, 3 to 4) vs. 10 (range, 4 to 24) months, P < 0.001] and presented with more severe pulmonary disease as indicated by a higher respiratory rate [63 (range, 60 to 73) vs. 50, (range, 40 to 60) P < 0.001], heart rate [160 (range, 136-180) vs. 140 (range, 120-152) P = 0.025] and a greater incidence of cyanosis (53% vs. 26%, P = 0.025). Clinical signs of HIV infection, occurring in 96% of children, were equally prevalent in both groups. High serum lactate dehydrogenase was the only laboratory investigation that distinguished PCP-infected from uninfected children [626 (range, 450 to 1098) vs. 307 (range, 243 to 465) units/l], P < 0.001. No radiologic features were found to be diagnostic of PCP. P. carinii was identified in 9 sputa and 6 bronchoalveolar lavage specimens, but all corresponding NPAs were negative. Seven of 15 (47%) children with PCP died while hospitalized compared with 24 of 136 (18%) without PCP [relative risk, 1.21 (range, 0.99 to 1.47), P = 0.008]. PCP is an important pathogen in HIV-infected infants in South Africa and is associated with a high mortality. Induced sputum is effective for obtaining lower respiratory tract secretions for diagnosis of PCP but an NPA is not useful.

Discontinuation of chemoprophylaxis against Pneumocystis carinii pneumonia in patients with HIV infection. HIV Outpatient Study (HOPS) Investigators.

HIV-infected patients with sustained immunologic improvement from antiretroviral therapy may be able to discontinue chemoprophylaxis against Pneumocystis carinii pneumonia (PCP). To compare PCP incidence in HIV-infected patients who had sustained CD4+ lymphocyte counts greater than 200 cells/mm3 and who either discontinued or continued PCP prophylaxis. Nonrandomized prospective cohort study. 10 HIV clinics in eight U.S. cities. 146 patients had follow-up visits for a mean of 18.2 months after discontinuation of PCP prophylaxis, and 345 patients who continued PCP prophylaxis had follow-up visits for a mean of 14.0 months. Incidence of PCP. Patients who discontinued PCP prophylaxis had higher maximum and minimum CD4+ cell counts and lower vira loads than patients who continued PCP prophylaxis. Pneumocystis carinii pneumonia did not develop in either group (upper 95% exact binomial confidence limit of incidence for those who discontinued PCP prophylaxis, 2.3/100 person-years). Discontinuation of PCP chemoprophylaxis may be appropriate for some HIV-infected ambulatory patients.

High Rates of Pneumocystis carinii Pneumonia in Allogeneic Blood and Marrow Transplant Recipients Receiving Dapsone Prophylaxis

Chemoprophylaxis for Pneumocystis carinii pneumonia (PCP) is routinely given after allogeneic blood or marrow transplantation. We evaluated the effectiveness of dapsone prophylaxis (50 mg orally twice daily, 3 times per week) compared with twice-weekly trimethoprim-sulfamethoxazole (TMP-SMZ) in preventing PCP after allogeneic blood or marrow transplantation. Patients included all (n=646) who received allogeneic blood or marrow transplants between 1 September 1993 and 31 December 1996 who survived at least 100 days after transplantation. A cohort of 111 dapsone recipients was compared with the remaining 535 who received TMP-SMZ. Ten patients developed PCP; 8 were taking dapsone. PCP incidence in the TMP-SMZ cohort was 0.37% versus 7.2% for dapsone. The relative risk for PCP associated with dapsone use was 18.8 (P<.001) and was not accounted for by age, clinical extensive chronic graft-versus-host disease, donor source, or malignant relapse. Dapsone prophylaxis at this dosage is associated with significantly higher rates of PCP than is TMP-SMZ after allogeneic marrow transplantation. We advise caution in prescribing alternatives to TMP-SMZ prophylaxis in this setting.

Can chemoprophylaxis against opportunistic infections be discontinued after an increase in CD4 cells induced by highly active antiretroviral therapy?

In the 'USPHS/IDSA Guidelines for Prevention of Opportunistic Infections in Persons Infected with Human Immunodeficiency Virus', the indications for chemoprophylaxis are based on nadir CD4 cell count. Many patients have, however, experienced an increase in CD4 cell count after the introduction of highly active antiretroviral therapy (HAART). To assess incidences of opportunistic infections after discontinuation of chemoprophylaxis in HIV-infected patients, who have experienced a HAART-induced increase in CD4 cell count. The Danish guidelines for chemoprophylaxis against opportunistic infections in HIV-infected patients were revised in late 1997, allowing discontinuation of chemoprophylaxis after initiation of HAART if the CD4 cell count remained above a specified limit for more than 6 months. Consecutive patients were followed, and incidences of opportunistic infections after discontinuation of chemoprophylaxis were assessed. A total of 219 patients discontinued Pneumocystis carinii pneumonia (PCP)-chemoprophylaxis (12% maintenance therapy). One case of PCP was diagnosed within 174 person-years (PY) of follow-up, resulting in an incidence of 0.6 cases/100 PY follow-up (95% confidence interval, 0.0-3.2). No cases of cerebral toxoplasmosis, cytomegalovirus chorioretinitis, or disseminated Mycobacterium avium infection were observed. Follow-up time for these was, however, limited. PCP-chemoprophylaxis can be safely discontinued after HAART-induced increase in CD4 cell count to more than 200 x 10(6) cells/l. Among consecutive patients who discontinue chemoprophylaxis according to well-defined guidelines, the observed incidence of PCP is below those reported earlier in patients with similar CD4 cell count.

Discontinuation of Pneumocystis carinii pneumonia prophylaxis after start of highly active antiretroviral therapy in HIV-1 infection

Highly active antiretroviral therapy (HAART) has improved rates of CD4-lymphocyte recovery and decreased the incidence of HIV-1-related morbidity and mortality. We assessed whether prophylaxis against Pneumocystis carinii pneumonia (PCP) can be safely discontinued after HAART is started. We investigated 7333 HIV-1-infected patients already enrolled in EuroSIDA, a continuing prospective observational cohort study in 52 centres across Europe and Israel. We did a person-years analysis of the rate of discontinuation of PCP prophylaxis and of the incidence of PCP after the introduction of HAART into clinical practice from July, 1996. The rate of discontinuation of primary and secondary PCP prophylaxis increased up to 21.9 discontinuations per 100 person-years of follow-up after March, 1998. 378 patients discontinued primary (319) or secondary (59) prophylaxis a median of 10 months after starting HAART. At discontinuation for primary and secondary prophylaxis, respectively, the median CD4-lymphocyte counts were 274 cells/microL and 270 cells/microL, the median plasma HIV-1 RNA load 500 copies/mL, and the median lowest recorded CD4-lymphocyte counts 123 cells/microL and 60 cells/microL. During 247 person-years of follow-up, no patient developed PCP (incidence density 0 [95% CI 0-1.5]). The risk of PCP after stopping primary prophylaxis, especially in patients on HAART with a rise in CD4-lymphocyte count to more than 200 cells/microL, is sufficiently low to warrant discontinuation of primary PCP prophylaxis. Longer follow-up is needed to confirm a similarly low risk for stopping secondary PCP prophylaxis.

Should prophylaxis for Pneumocystis carinii pneumonia in solid organ transplant recipients ever be discontinued?

Solid organ transplant recipients are at risk for Pneumocystis carinii pneumonia (PCP), but the risk of PCP beyond 1 year is poorly defined. We identified 25 cases of PCP in 1,299 patients undergoing solid organ transplantation between 1987 and 1996 at The Cleveland Clinic Foundation (4.8 cases per 1,000 person transplant-years [PTY]). Ten (36%) of 28 PCP cases (transplantation was performed before 1987 in three cases) occurred > or = 1 year after transplantation, and no patient developed PCP while receiving prophylaxis for PCP. The incidence of PCP during the first year following transplantation was eight times higher than that during subsequent years. The highest rate occurred among lung transplant recipients (22 cases per 1,000 PTY), for whom the incidence did not decline beyond the first year of transplantation. We conclude that the incidence of PCP is highest during the first year after transplantation and differs by type of solid organ transplant. Extending the duration of PCP prophylaxis beyond 1 year may be warranted for lung transplant recipients.

Pneumocystis carinii pneumonia incidence and chemoprophylaxis failure in ambulatory HIV-infected patients. HIV Outpatient Study (HOPS) Investigators.

Pneumocystis carinii pneumonia (PCP) remains the most frequently reported serious opportunistic infection in AIDS patients and the second highest cause of mortality among persons with AIDS in the United States, despite the availability of effective chemoprophylaxis. To evaluate incidence of PCP and determinants of PCP chemoprophylaxis failure, we analyzed data from 2842 patients visits to infectious diseases physicians at 10 HIV clinics (eight private and two public) in eight U.S. cities from January 1992 through June 1996 as part of the HIV Outpatient Study (HOPS). We performed a time-dependent regression analysis to examine potential determinants of PCP chemoprophylaxis failure. The incidence of chemoprophylaxis failure was 4.6 PCP cases/100 person-years on chemoprophylaxis; these cases represent 67% of all incident episodes of PCP. In a multivariate analysis, the only significant predictors of chemoprophylaxis failure were the use of agents other than trimethoprim-sulfamethoxazole (TMP-SMX), history of prior PCP, and a CD4+ T-lymphocyte cell count of <50 cells/microl. Dosing or frequency of TMP-SMX did not seem to influence risk of chemoprophylaxis failure. Chemoprophylaxis failure, especially among those with the most advanced immunosuppression or history of prior PCP, was the most significant source of new PCP cases in the HOPS cohort and thus represents one of the largest contributors to morbidity and mortality in this cohort.

Pneumocystis and pneumocystosis in Europe at the end of the 20th century.

Pneumocystis carinii was described as a new microorganism in the lungs of rats living in Paris by Delanoe and Delanoe in 1912 [1]. In the early 1950s, the first cases of human pneumocystosis were described in orphans and in infants living in eastern Europe [2, 3]. Then Pneumocystis carinii pneumonia (PCP) was reported as an opportunistic disease in patients treated with immunosuppressive therapy [4] for malignancy, hemopathies or cancer. The significant increase in PCP incidence at the beginning of the 1980s has been related to the emergence of the AIDS epidemic [5]. In the last 10 years, important improvements have occurred in the field of diagnosis and therapy strategies, simultaneously, due to the interest of an increasing number of research teams. From the diagnostic point of view, more sensitive techniques such as immunofluorescence with monoclonal antibodies [6] and PCR [7–10] have been proposed with less invasive samples such as bronchoalveolar lavage, induced sputum [11] and more recently oral washes [12–14]. Since the beginning of the 1990s, primary prophylaxis has been proposed for HIV-infected patients with a CD4 count below 200/mm3[15]. Trimethoprim-sulfamethoxazole (TMT-SMX) is the most efficient molecule, but others can be proposed such as aerosolized pentamidine [16]. The evolution of antiretroviral therapies, mainly new antiretroviral associations for HIV infection, will change the wide spread of PCP, but many questions are …

Pneumocystis carinii pneumonia prophylaxis and early clinical manifestations of severe perinatal human immunodeficiency virus type 1 infection. Northern California Pediatric HIV Consortium.

Some children with perinatal HIV infection develop early progression to severe symptoms (Category C) within the first 4 years of life. Prophylactic therapy with trimethoprim-sulfamethoxazole (TMP/SMX) may affect progression by decreasing the incidence of Pneumocystis carinii pneumonia (PCP). HIV progression to Category C in the first 3 years of life was retrospectively analyzed in a population-based cohort of children with perinatal HIV infection followed for > or = 3 years from birth. Time to development of Category C and clinical patterns of new Category C diagnoses were examined in relation to patterns of PCP prophylaxis before diagnosis. Fifty-eight of 147 children developed 67 initial category C diseases by 3 years of age: PCP (n=24), encephalopathy (n=22), other opportunistic infections (n=19) and wasting (n=2). Before diagnosis therapy included TMP/ SMX and zidovudine (ZDV) (n=11), TMP/SMX alone (n=7), ZDV alone (n=1) and neither (n= 39). The probability of developing a Category C diagnosis after 2 years was significantly lower among children who received TMP/SMX compared with those who did not (29%, TMP/SMX vs. 45%, no TMP/SMX; 30%, TMP and ZDV vs. 45%, no therapy; P < 0.01). The frequency of PCP was significantly lower and that of HIV encephalopathy was significantly higher among children receiving TMP/SMX +/- ZDV before Category C diagnosis than among children receiving neither. In this study PCP prophylaxis was associated with longer time to Category C diagnoses in the first 3 years of life. This association was related to a decreased incidence of PCP and an increased incidence of encephalopathy as the first Category C diagnosis among children who received TMP/SMX.

High-resolution CT in the evaluation of clinically suspected Pneumocystis carinii pneumonia in AIDS patients with normal, equivocal, or nonspecific radiographic findings.

We prospectively studied AIDS patients with a high clinical pretest probability of Pneumocystis carinii pneumonia (PCP) in whom chest radiographic findings were normal, equivocal, or nonspecific with high-resolution CT (HRCT) to determine the incidence of PCP in these patients, to assess the diagnostic accuracy of HRCT for the presence or absence of PCP, to evaluate the role of HRCT in patient management, and to determine the clinical outcome of all patients 1 month after evaluation. All patients were referred to the Division of Pulmonary and Critical Care Medicine for diagnosis of clinically suspected PCP. Thirty-three patients were prospectively evaluated with HRCT within 24 hr of diagnostic bronchoalveolar lavage; 18 other patients who underwent HRCT were managed according to the HRCT interpretation and followed up clinically. All HRCT scans were independently reviewed by three chest radiologists; patchy or nodular ground-glass attenuation was considered to indicate "possible PCP." The incidence of PCP was 12% (6/51). The sensitivity of HRCT was 100%; specificity, 89%; and accuracy, 90% (p < .005). We had five false-positive and no false-negative interpretations. Some form of "airways disease" (n = 23) was the single most common HRCT interpretation. HRCT may allow exclusion of PCP in patients with findings that are normal, equivocal, or nonspecific on chest radiographs. Empiric therapy or immediate bronchoscopy can be avoided in many patients on the basis of the HRCT findings.

Fulminant Pneumocystis carinii Pneumonia in 4 Patients With Dermatomyositis

Between 1989 and 1996, 4 cases of Pneumocystis carinii pneumonia (PCP) were observed in patients seronegative for the human immunodeficiency virus who were receiving corticosteroid therapy for dermatomyositis in our institution. These cases were considered unusual in light of the short delay of their onset after initiation of immunosuppressive therapy and their fulminant course: 3 of these patients died of PCP occurring during the first month of treatment with prednisone. In all 4 patients lymphopenia was observed before the initiation of corticosteroid treatment and low CD4 and CD8 cell counts were evident at the time of PCP. These observations support the view of an increase in both the severity and incidence of PCP in patients without human immunodeficiency virus infection and question the need for a primary prophylaxis in patients with connective tissue diseases receiving high-dose corticosteroid therapy.

PNEUMOCYSTIS CARINII PNEUMONIA

Pneumocystis carinii pneumonia (PCP) remains an important complication of AIDS. Advances have been made in establishing the taxonomy of the organism but the life cycle of the organism and pathogenetic mechanisms of disease remain obscure. In HIV patients the incidence of PCP has decreased because of widespread use of prophylaxis and survival of those with PCP has improved with use of adjunctive corticosteroid therapy. Less toxic drug therapies are still needed as well as better noninvasive diagnostic techniques.

Pneumocystis Carinii Pneumonia. Review of 32 Cases in Immunocompromised Hosts

SummaryThe records of patients in whom Pneumocystis carinii pneumonia (PCP) was diagnosed between January 1989 and December 1991 were reviewed. Thirty-two patients-all immunocompromised-were included in the study: 41% were HIV-positive and 59% HIV-negative. In 23 patients (72%) concomitant pathogens were isolated, most frequently Cytomegalovirus. Presenting symptoms included fever (97%), cough (75%) and dyspnea (63%). All HIV-infected patients had a THymphocyte count below 200/mm (or 20%). The majority of patients (80%) treated with trimethoprim-sulfamethoxazole experienced adverse eventswhich were usually well tolerated, so that a therapy change was necessary in only 12% of patients. PCP was fatal in 34% of the patients. Respiratory failure requiring mechanical ventilation carries a poor prognosis.The ratio of non-AIDS/AIDS patients infected with PC is increasing. This increase is due to the growing contribution of patients treated with immunosuppressive agents and patients with disease-associated immunodeficiencies other than AIDS. Our study suggests that treatment of PCP is mor successful with early diagnosis. In addition, as mortality rate is high in non-AIDS patients, our data suggest that die more frequent use of PCP prophylaxis in patients given immunosuppressive drugs, might reduce the incidence of PCP and PCP related mortality.

Indirect muscarinic receptor activation by pentamidine on airway smooth muscle.

1. Pentamidine is routinely used to reduce the incidence of Pneumocystis carinii pneumonia in patients infected with human immunodeficiency virus, but it has been described as inducing pulmonary adverse effects, such as cough and bronchospasm. 2. In this paper we have investigated the effects of pentamidine on guinea-pig isolated main bronchi and human isolated bronchi. Pentamidine induced a concentration-dependent contraction in both preparations with pD2 values of 9.64 +/- 0.07 (n = 8) and 9.73 +/- 0.06 (n = 8) and a maximal effect (Emax) of 40 +/- 4% and 34 +/- 5% of the response to acetylcholine (1 mM) in guinea-pig and human bronchi respectively. Atropine (0.01 to 0.1 microM) and the muscarinic M3 receptor antagonist, hexahydro-siladiphenidol (0.1 and 1 microM) inhibited pentamidine-induced concentration-responses in both preparations in a non-competitive manner, whereas only high concentrations of the M1 receptor antagonist pirenzipine (1 microM) inhibited pentamidine concentration-response curves. 3. The cholinesterase inhibitor, tacrine (1 microM), potentiated the effect of pentamidine; in contrast, morphine inhibited pentamidine-induced responses. 4. The bronchoconstrictor effect of pentamidine on guinea-pig and human isolated bronchi was not modified by the H1 histamine receptor antagonist, mepyramine, by indomethacin or by the neurokinin NK1 and NK2 receptor antagonists, CP-96,345 and SR 48969 respectively, suggesting that neither histamine receptor stimulation, arachidonic acid derivative formation, nor tachykinin release are involved in pentamidine-induced contraction of human and guinea-pig airways. 5. Our overall results suggest that pentamidine induces contraction of guinea-pig and human isolated bronchi through prejunctional cholinergic nerve stimulation.

Patterns of morbidity and mortality in AIDS patients on Pneumocystis carinii prophylaxis who died during hospital admission: A report of 50 diseased patients

Background: Since the introduction of prophylaxis against Pneumocystis carinii pneumonia (PCP) the pattern of illnesses related to AIDS has changed. PCP prophylaxis may delay the first AIDS-defining illness (ADI) and shifts the clinical manifestations of AIDS to illnesses other than PCP. Methods: Morbidity and mortality patterns were studied of the first 50 diseased HIV-infected patients who died during hospital admission since the inroduction of PCP prophylaxis. Results: The survival of patients after the diagnosis of AIDS in all patients was 13 months, with no difference in survival between patients who were on zidovudine for more than 6 months before the diagnosis of AIDS and those who were not on zidovudine. PCP was seen in 10 patients as the first ADI who were unaware of being HIV-infected and two during the course of their disease due to inappropriate use of prophylaxis. None of the 50 patients died from PCP. Twenty-five patients suffered from complications of the central nervous system (CNS) and these were the major immediate cause of death. Conclusions: Our findings show that due to the use of PCP prophylaxis the incidence of PCP is low, but that PCP is still a common disease in patients unaware of their HIV infection. On the other hand, our findings suggest that CNS disease is the major immediate cause of death in patients on PCP prophylaxis.

Incidence of Pneumocystis carinii pneumonia after renal transplantation. Impact of immunosuppression.

The incidence and potential risk factors of Pneumocystis carinii pneumonia (PCP) in our population of renal transplant recipients were analyzed retrospectively. Of 1427 patients who received transplants between January 1986 and June 1994, 1192 were evaluated. Four different immunosuppressive regimens were applied: (1) cyclosporine (CsA) + prednisolone (Pred), (2) CsA + azathioprine (Aza, 2 mg/kg/day) + Pred, (3) CsA + Aza + antithymocyte globulin, and (4) (after December 1, 1993, European multicenter trial) FK506 + Aza (1 mg/kg/day) + Pred. No prophylaxis against PCP was performed. Before December 1, 1993, three PCPs in 494 patients on protocol 2 or 3 occurred (0.6%). Afterward, seven PCPs in 77 patients occurred (9%): three in 38 patients on protocol 2 (7.8%) and four in 28 patients on protocol 4 (14.3%). Comparing patients with PCP on CsA and FK506, the mean Aza dose was 2.40 and 1.32 mg/kg/day, five and two patients received additional steroids, antibody treatment was used in three and no patients, and CMV infections occurred in five and two patients, respectively. The incidence of PCP with a moderate CsA-based immunosuppressive regimen is low and seems to occur only in cases of additional immunosuppressive cofactors. Despite a general increase of PCP, its incidence was highest in patients on FK506 with fewer immunosuppressive cofactors. Thus, prophylaxis against PCP after renal transplantation should be performed, if not in every renal transplant recipient, at least in case of treatment with additional steroids, antibodies, or FK506.

Zinc levels and infections in hospitalized patients with AIDS

Impaired cellular and humoral immunity and phagocytic function have been attributed to zinc deficiency. This study examined the association between low serum zinc concentration and opportunistic infections in hospitalized patients with the acquired immune deficiency syndrome (AIDS). We examined the records from all 505 inpatient consultations performed by our Nutrition Service from May 1992 through June 1994. The medical records from all 228 patients with AIDS with known serum zinc levels (determined by atomic absorption spectrophotometry) were reviewed. The length of HIV seropositivity, most recent CD4 count, presence of diarrhea, and degree of malnutrition were noted. The principal diagnosis accounting for the admission was grouped according to the type of infection: Pneumocystis carinii pneumonia (PCP), viral, fungal, bacterial, and other. Sixty-seven patients (29%) had abnormally low serum zinc levels (LSZ < 55 μg/dL), 49 patients (21%) had borderline low serum zinc (BSZ ≥ 55 and ≤ 65 μg/dL), and 112 (49%) patients had normal serum zinc levels (NSZ > 65 μg/dL). There was no significant difference among the groups in CD4 count, length of HIV seropositivity, presence of diarrhea, or severity of malnutrition. Patients with zinc deficiency (LSZ) had a significantly higher incidence of bacterial infection than did patients with normal zinc. Patients with borderline zinc levels had an intermediate incidence of bacterial infection. There were no significant differences among the three groups in the incidence of PCP, viral, or fungal infections. Severe zinc deficiency was noted in 29% and borderline levels in an additional 21% of hospitalized AIDS patients. A low zinc level was not associated with the length of HIV seropositivity, CD4 count, or degree of malnutrition. Hypozincemia was associated with an increased incidence of concomitant systemic bacterial infections.

Aerosolized Pentamidine as Alternative Primary Prophylaxis Against Pneumocystis carinii Pneumonia in Adult Hepatic and Renal Transplant Recipients

To examine the safety and efficacy of aerosolized pentamidine (AP) as alternative primary prophylaxis against Pneumocystis carinii pneumonia (PCP) in adult liver and kidney transplant recipients. Retrospective review of medical records. Tertiary care urban teaching hospital with active liver and kidney transplant programs. Adult liver and kidney transplant recipients intolerant of trimethoprim-sulfamethoxazole (TMP-SMX) therapy and referred to the AP clinic between June 1991 and December 1994. Each patient received monthly AP, 300 mg, delivered by a nebulizer (Respirgard-II), preceded by inhaled albuterol, 180 micrograms. During the period of follow-up, information related to side effects of AP and incidence of PCP was recorded. A total of 35 patients were identified, 18 liver and 17 kidney transplant recipients. Fourteen patients received AP as initial prophylaxis because of prior sensitivity to TMP-SMX. In another 19 patients, initial TMP-SMX therapy was discontinued for leukopenia (5), elevated liver function test values (4), rash (3), nausea (2), renal failure (2), seizure (2), and thrombocytopenia (1). In addition, two patients received AP in the setting of organ rejection. Liver transplant recipients received AP for an average of 4.28 +/- 1.6 months, and renal transplant recipients received AP for an average of 5.71 +/- 4.3 months. Adverse effects of AP included bronchospasm (two), dyspnea (one), cough (one), and nausea (one). AP therapy was discontinued in only one patient due to severe bronchospasm. There were no cases of PCP in the 35 patients receiving AP. These observations suggest that AP is well tolerated and may be an effective alternative for PCP prophylaxis in adult liver and kidney transplant recipients intolerant to TMP-SMX therapy.

Respiratory infections in HIV-negative immunocompromised patients.

The number of immunosuppressed patients is increasing, with many being managed by community physicians. Encouraging success in vaccinating some patients with Hodgkin's disease against encapsulated organisms has been reported. The significance of and management of tuberculosis in solid organ transplants is being defined. Fungal infection remains a problem, but pathogenesis and treatment are being clarified. The overall incidence of Pneumocystis carinii pneumonia is low, but it is being seen in patients without malignant disease, especially those with Wegener's granulomatosis. Many authors have tried to establish risk factors that will allow development of clear indications for prophylaxis in these patients. New approaches to cytomegalovirus infection are discussed as well as the role of community-acquired viruses in causing disease in the immunosuppressed population.