Concomitant Pulmonary Infection Research Articles

Concomitant or sequential pulmonary infection with non-tuberculous mycobacteria and Aspergillus.

Non-tuberculous mycobacteria (NTM) and Aspergillus are ubiquitous organisms that have the potential to cause significant pulmonary disease in certain clinical contexts. An association is known to exist between NTM and Aspergillus lung infections. However, it is unclear if NTM infection predisposes to Aspergillus infection or vice versa. It is also unclear whether treatment for one results in a favourable ecological niche that facilitates the growth of the other and promotes subsequent clinical disease. An improved understanding of the link between these two pulmonary pathogens is critical to guide improvements in clinical practice, and ultimately, enhance outcomes among patients who are at risk of experiencing these infections, either concomitantly or sequentially. Here, we discuss the association between pulmonary NTM and Aspergillus infections. We address the frequency with which coinfection or sequential infections are reported to occur, predisposing risk factors that have been identified and the impact on clinical outcomes. Current data on the mechanistic links between NTM and Aspergillus lung infections are also considered. The potential implications for routine clinical practice are explored.

Tuberculosis revisted: classic imaging findings in childhood

Tuberculosis (TB) remains one of the major public health threats worldwide, despite improved diagnostic and therapeutic methods. Tuberculosis is one of the main causes of infectious disease in the chest and is associated with substantial morbidity and mortality in paediatric populations, particularly in low- and middle-income countries. Due to the difficulty in obtaining microbiological confirmation of pulmonary TB in children, diagnosis often relies on a combination of clinical and radiological findings. The early diagnosis of central nervous system TB is challenging with presumptive diagnosis heavily reliant on imaging. Brain infection can present as a diffuse exudative basal leptomeningitis or as localised disease (tuberculoma, abscess, cerebritis). Spinal TB may present as radiculomyelitis, spinal tuberculoma or abscess or epidural phlegmon. Musculoskeletal manifestation accounts for 10% of extrapulmonary presentations but is easily overlooked with its insidious clinical course and non-specific imaging findings. Common musculoskeletal manifestations of TB include spondylitis, arthritis and osteomyelitis, while tenosynovitis and bursitis are less common. Abdominal TB presents with a triad of pain, fever and weight loss. Abdominal TB may occur in various forms, as tuberculous lymphadenopathy or peritoneal, gastrointestinal or visceral TB. Chest radiographs should be performed, as approximately 15% to 25% of children with abdominal TB have concomitant pulmonary infection. Urogenital TB is rare in children. This article will review the classic radiological findings in childhood TB in each of the major systems in order of clinical prevalence, namely chest, central nervous system, spine, musculoskeletal, abdomen and genitourinary system.Graphical

Emerging Maripa Hantavirus as a Potential Cause of a Severe Health Threat in French Guiana.

We describe the clinical parameters and management of nine confirmed cases of hantavirus pulmonary syndrome reported in French Guiana since 2008. All patients were admitted to Cayenne Hospital. Seven patients were men and the mean age was 48 years (range, 19-71 years). Two phases characterized the disease. The prodromal phase was characterized by fever (77.8%), myalgia (66.7%), and gastrointestinal symptoms (vomiting and diarrhea; 55.6%) starting, on average, 5 days before the illness phase, which was characterized by respiratory failure in all patients. Five patients died (55.6%) and the length of stay in the intensive care unit was 19 days (range, 11-28 days) for survivors. Detection of two back-to-back recent cases highlights the reason to screen for hantavirus infection during the nonspecific phase of the disease, in particular when concomitant pulmonary infection and digestive disorders are observed. Specific longitudinal serological surveys must also be used to identify other potential clinical forms of the disease in French Guiana.

Association of ovine gammaherpesvirus 2 with an outbreak of acute respiratory disease in dairy cattle

This study investigated the cause of an outbreak of an acute respiratory disease syndrome followed by episodes of diarrhea in a dairy cattle herd from Southern Brazil. Deep nasal swabs (DNS) from asymptomatic calves, calves with pulmonary discomfort, and diarrheic calves after episodes of respiratory distress were used in molecular assays designed to detect the principal pathogens associated with bovine respiratory disease (BRD). Fecal samples were used for the molecular detection of bovine enteric disease agents. Pulmonary tissues from three calves and a cow that died were evaluated by molecular assays to identify 11 agents associated with the development of BRD. The intestinal and pulmonary fragments of one calf and the cow revealed atrophic enteritis and interstitial pneumonia by histopathology, respectively. Immunohistochemistry (IHC) identified intralesional antigens of a malignant catarrhal fever virus, genus Macavirus, within epithelial cells of the lungs and intestines. Molecular assays amplified ovine gammaherpesvirus 2 (OvGHV2) from most of the DNS, and the pulmonary and intestinal fragments from the animals that died, confirming that the Macavirus identified by IHC was OvGHV2. Concomitant pulmonary infections of OvGHV2 with bovine gammaherpesvirus 6 and bovine coronavirus were identified. Additionally, bovine viral diarrhea virus 1b and Aichivirus B were detected in the fecal samples. These findings demonstrated that OvGHV2, a Macavirus, was the disease agent most frequently (81.2%; 13/16) associated with singular pulmonary infections during this outbreak of BRD, suggesting that this virus may be another potential agent of respiratory disease of cattle.

S3732 A Unique Manifestation of Tuberculosis in the Gut

Introduction: Abdominal manifestations of tuberculosis (TB) can involve the peritoneum, gastric body, intestinal tract, pancreas, perianal region, hepatobiliary region, and surrounding lymph nodes in patients with associated risk factors. We present a patient with known TB exposure and a gastric mass with associated lymphadenopathy (LAD), later determined to be secondary to gastric tuberculosis. Case Description/Methods: An 18 year old female with no past medical history presented with several months of upper abdominal pain exacerbated by deep breathing. A prior esophagogastroduodenoscopy (EGD) revealed a submucosal gastric ulcer (1), and further evaluation with an EGD and endoscopic ultrasound (EUS) revealed a peri-gastric mass with retroperitoneal and portocaval LAD (2). Fine needle aspiration (FNA) of the mass revealed granulomatous inflammation with focal necrosis (3) and rare acid fast bacilli seen on Fite stain (4). Further history on follow up revealed a close household contact had recently tested positive for TB. The patient was started on full treatment with Rifampin, Isoniazid, Pyrazinamide, and Ethambutol (RIPE) for gastric TB, with improvement in symptoms noted on follow up. A repeat EGD with EUS was performed 7 months after the initial, with observed improvement in retroperitoneal LAD and no organisms seen on FNA. (Figure) Discussion: This case illustrates a unique presentation of gastric TB in a patient, later determined to have been exposed to a close contact. The presenting symptom of non-remitting abdominal pain along with prior endoscopic findings of a submucosal gastric ulcer prompted further evaluation, which led to the histologically confirmed diagnosis of gastric TB and the initiation of appropriate treatment. Gastrointestinal (GI) tract involvement of TB occurs in about 11% of cases, and is associated with concomitant pulmonary TB infection in only about 25% of cases. Mycobacterium tuberculosis is thought to infiltrate the GI tract by adhering to submucosal lymphoid tissue, with caseous necrosis leading to ulceration over 2-4 weeks. Diagnostic findings include circumferential ulceration surrounded by inflammation with submucosal granulomas seen on biopsy, as seen in this case. Patients often clinically improve after treatment with RIPE, though surgical management is warranted when complications exist. GI manifestations of TB should be considered in patients with positive risk factors and unexplained persistent abdominal symptoms, with treatment initiated as soon as the diagnosis is confirmed.Figure 1.: 1) Gastric cardia ulcer seen on EGD 2) Peri-gastric lymphadenopathy seen on EUS 3) 10x Hematoxylin & Eosin (H&E) stain of gastric tissue showing granulomatous inflammation 4) 60x Fite stain of gastric tissue showing acid fast bacilli.

P144 The uncommon meets the common: Invasive Aspergillosis and tuberculosis co-infection in non-neutropenic patients— arare association

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMBackground and ObjectiveInvasive aspergillosis (IA) is known to occur in immunocompromised patients including neutropenic patients. But, recently increasing cases have been reported in patients with non-classical risk factors and non-neutropenic patients like diabetes mellitus, chronic lung disease, HIV infection, critically ill patients, etc. According to ISHAM these non-classical risk factors should be included in EORTC/MSG host criteria for diagnosis of invasive aspergillosis.India has a high tuberculosis (TB) burden, and this is always considered as the first differential for any patient with fever, cough, hemoptysis, and weight loss. Post-tubercular chronic pulmonary aspergillosis common reported condition. However, co-infection of active TB and invasive aspergillosis is less reported. This co-infection could be one of the contributors of high morbidity and mortality in cases with tuberculosis.We hereby present a series of five cases of TB concomitant with invasive aspergillosis in non-neutropenic patients.MethodsThis is a prospective observational study, all patients admitted with molecular diagnosis (GeneXpert) of tuberculosis and with at least one non-classical risk factor for invasive aspergillosis were subjected to further evaluation. Diagnosis of invasive aspergillosis was considered in patients who had at least one clinical and one mycological EORTC criteria. Galactomannan level in different samples was measured via PlateliaTM ELISA. The efficacy of different antifungals and outcomes were analyzed.ResultsTotal 57 patients with TB underwent for evaluation of invasive aspergillosis. Among them, five patients were diagnosed to have concomitant TB and invasive aspergillosis, of which three cases of CNS TB and CNS aspergillosis and two had concomitant pulmonary infections. The average age was 31 ± 12 years with a female preponderance (4/5). Two patients were HIV positive, while among non-HIV patients, one had CD4 cytopenia (CD4-171). One patient had no known predisposing factor. Radiologically, most common pulmonary lesions were patchy consolidation with centrilobular nodules with tree in bud appearance, while CNS lesions showed multiple ring-enhancing lesions. All the patients had CBNAAT positive, two from BAL sample, 1 from CSF, and 1 from the lymph node. Rifampicin was sensitive in all, except one who had rifampicin resistance indeterminate. Of these patients, four were probable invasive aspergillosis satisfying the host, mycological and clinical factors as per the EORTC/MSGERC 2021 guidelines. The treatment of coinfection is challenging due to the interaction of rifampicin with voriconazole, which is the drug of choice for invasive aspergillosis. Here, 3 patients were treated with Inj amphotericin B, while the other 2 patients were started on voriconazole with rifampicin sparing regimen for TB. Of the 5 patients, 4 patients survived with excellent response to the treatment, with one fatality.ConclusionThe possibility of concurrent TB and invasive aspergillosis in non-neutropenic hosts should be considered to avoid devastating outcomes. The lack of clinical suspicion may result in misdiagnosis, and most importantly, the chronicity of the infection makes it indistinguishable from TB. Moreover, the co-administration of antifungal and anti-TB medications presents significant therapeutic challenges necessitating thorough evaluation and monitoring.

Concomitant Pulmonary Tuberculosis and Invasive Aspergillosis Infection in an Immunocompetent Host.

Pulmonary tuberculosis (TB) is a common infection in developing countries and is associated with low socioeconomic status. It is considered a serious infection due it its long-term sequelae. Post-TB lung disease decreases life expectancy and increases the risk of recurrent TB infection. It also significantly increases the risk of other bacterial and fungal infections. Aspergillosis develops in the cavitary lesions of TB, worsening them and resulting in a deteriorating clinical situation. Concomitant pulmonary TB (PTB) and invasive aspergillosis is uncommon, particularly in the absence of factors that suppress the immune system. In this report, we describe the case of a healthy young adult without previous structural lung damage who presented with primary PTB and acute invasive aspergillosis infection, discuss the treatment dilemma and provide a literature review.LEARNING POINTSAspergillosis can mimic tuberculosis (TB) infection.Concomitant pulmonary TB and invasive aspergillosis is uncommon.The co-administration of antifungal and anti-TB medications presents significant therapeutic challenges.

Immunological Evaluation for Personalized Interventions in Children with Tuberculosis: Should It Be Routinely Performed?

Childhood tuberculosis (TB) is a significant public health problem and the ninth leading cause of death worldwide. Progression of Mycobacterium tuberculosis infection to active disease depends on mycobacterial virulence, environmental diversity, and host susceptibility and immune response. In children, malnutrition and immaturity of the immune system contribute to an inadequate immune response. Coinfections, though rarely described in TB, might be associated with host immune deficiencies. Here, we describe the immunological evaluation of eight pediatric patients infected with a member of the M. tuberculosis complex, most of them with concomitant pulmonary infections (bacteria, viruses, or fungi). We assessed the functionality of several innate immunity receptors, IL-12 receptor, and IFN-γ receptor, as well as the antioxidant levels (glutathione), which are essential mechanisms for fighting intracellular pathogens such as M. tuberculosis. This study is aimed at developing a thorough immunological evaluation of patients with TB and a coinfection.

Peripheral CD19+CD24highCD38high B-regulatory cells in lung transplant recipients

BackgroundThe role of CD19+CD24highCD38high B-regulatory cells in solid-organ Transplant (Tx) in acceptance are still scarce. In previous studies on kidney transplant recipients may suggest a protective role of this cell subtype in graft tolerance and the existence of a cross talk between B-and T-regulatory clones. In lung transplantation, the role of B-regulatory cells has never been investigated. In a murine tracheal transplantation model, this subset seems able to prevent tracheal obliteration when in combination with rapamycin. Aim of this study is to analyze peripheral CD19+CD24highCD38high B-reg cells counts in a cohort of lung recipients, their association with several clinical and pharmacological variables and their possible association with T regulatory cell. MethodsFrom Jan 2009 to Dec 2014, 117 lung Tx recipients were submitted to an immunological follow up I-FU(median: 108.7 months (6.7–310.5)). Immunological follow up consisted of a complete blood peripheral immuno-phenotype, inclusive of CD19+CD24highCD38high B-cells (globally 1106 determinations). We tested the association between B-reg and relevant variables by linear or regression models for repeated measures, adjusting for time from Tx. ResultsAmong all variables analyzed at multivariate analysis: chronic rejection (OR − 0.19, p = .039), use of Mycophenolate (OR − 0.38, p < .001) and the presence of a concomitant pulmonary infection of S. aureus (OR 0.66, p = .002) and A. fumigatus (OR 0.50, p = .009) were significantly associated to B-reg cell.No significant correlation between CD19+CD24highCD38high B-reg cells and T-reg cells counts was found in our cohort. ConclusionsOur present data highlight, for the first time, that this cell subset might participate in long-term lung graft acceptance mechanisms.

Diagnostic value of KL-6 in idiopathic interstitial pneumonia.

Idiopathic interstitial pneumonia (IIP) can induce type II alveolar epithelial cell proliferation and pulmonary basement membrane damage and subsequent release of Krebs von den Lungen-6 antigen (KL-6) to the bloodstream. This study investigated the diagnostic and prognostic value of serum KL-6 levels for IIP. One hundred five patients with lung disease were divided into IIP (n=75) and non-IIP groups (n=30) according to pathological and computed tomography findings. Serum KL-6 levels were evaluated in blood samples from all subjects. Nineteen IIP group patients were also subjected to a longitudinal study of disease progression and serum KL-6 levels over time. Serum KL-6 levels were significantly higher in the IIP group vs. the non-IIP group [1,096.0 (565.0-1,544.0) vs. 226.0 (173.5-346.5) U/mL; P<0.01]. Within the IIP group, serum KL-6 levels differed significantly between patients with and without concomitant disease or pulmonary infection (Z=-2.475, P=0.013). In a receiver operating characteristic (ROC) curve analysis, the area below the curve for serum KL-6 was 0.911 [95% confidence interval (CI): 0.847-0.975, P<0.001], indicating a good diagnostic performance for IIP, with a cut-off level of 485 U/mL, sensitivity of 85.33%, specificity of 90.00%, positive predictive value (PPV) of 95.52%, negative predictive value (NPV) of 71.05%, and Kappa value of 0.70. Accordingly, the serum KL-6 and clinical diagnostic results were consistent. Moreover, in the longitudinal study, the serum KL-6 levels differed significantly from before to after treatment in patients with exacerbated or improved disease (P=0.004 and P=0.043, respectively), whereas no obvious changes were observed in patients with stable disease (P=0.692). The serum KL-6 level is a valuable and significant diagnostic marker of IIP and a useful predictor of clinical prognosis.

The impact of concomitant pulmonary infection on immune dysregulation in Pneumocystis jirovecii pneumonia.

BackgroundConcurrent infection may be found in Pneumocystis jirovecii pneumonia (PJP) of non-acquired immunodeficiency syndrome (AIDS) patients, however, its impact on immune dysregulation of PJP in non-AIDS patients remains unknown.MethodsWe measured pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-8, IL-17, monocyte chemoattractant protein-1 (MCP-1) and anti-inflammatory cytokines including IL-10 and transforming growth factor (TGF)-β1 and IL-1 receptor antagonist (IL-1RA) and inflammatory markers including high mobility group box 1, Krebs von den Lungen-6, receptor for advanced glycation end product, advanced glycation end product, surfactant protein D in bronchoalveolar lavage fluid (BALF) and blood in 47 pure PcP and 18 mixed PJP and other pulmonary infections (mixed PJP) in non-AIDS immunocompromised patients and explored their clinical relevance. The burden of Pneumocystis jirovecii in the lung was determined by counting number of clusters of Pneumocystis jirovecii per slide and the concentration of β-D-glucan in BALF. PJP severity was determined by arterial oxygen tension/fraction of inspired oxygen concentration ratio, the need of mechanical ventilation and death.ResultsCompared with pure PJP group, mixed PJP group had significantly higher BALF levels of IL-1β, TNF-α and IL-8 and significantly higher blood levels of IL-8. The BALF ratios of TNF-α/IL-10, IL-8/IL-10, IL-1β/IL-10, TNF-α/TGF-β1, IL-8/TGF-β1, IL-1β/TGF-β1 and IL-1β/IL-1RA were significantly higher in mixed than in pure PJP patients. There was no significant difference in clinical features and outcome between pure and mixed PJP groups, including inflammatory biomarkers and the fungal burden. In pure PJP patients, significantly higher BALF levels of IL-8 and the ratios of IL-8/IL-10, IL-1β/TGF-β1, MCP-1/TGF-β1, MCP-1/IL1RA and IL-8/TGF-β1 were found in the patients requiring mechanical ventilation and in non-survivors.ConclusionsIn summary, concurrent pulmonary infection might enhance immune dysregulation of PJP in non-AIDS immunocompromised patients, but did not affect the outcome as evidenced by morbidity and mortality. Because of limited number of cases studied, further studies with larger populations are needed to verify these issues.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2466-14-182) contains supplementary material, which is available to authorized users.

Prospective Weekly Surveillance Of Respiratory Viruses Using Viral Culture In First 100 Days After Allogeneic Stem Cell Transplantation

BackgroundRespiratory viral infections (RVI) in early phase after allogeneic stem cell transplantation (alloSCT) are associated with high morbidity and mortality and may result in institutional outbreak. So far, there have been few reports on incidence of RVI in alloSCT recipients with prospective surveillance. MethodsWe prospectively surveyed 247 recipients (271 transplants)who received alloSCT in Toranomon Hospital from June 2010 to May 2012. Oropharyngeal swab samples were collected weekly from each patient starting from 1 week before transplantation until 100 days after SCT. Respiratory viruses (RV) were isolated by viral culture (HHMV method). Symptoms related to RVI including fever, cough, sputum, and rhinorrhea were surveyed with patient questionnaire form. To exclude concomitant infection, culture of sputum and blood, serological tests (such as Aspergillus-galactomannan and beta-D-glucan), antigen test of influenza (Flu) and PCR of respiratory syncytial virus (RSV), parainfluenzavirus (PIV) type 3, and adenovirus (ADV) were routinely performed in symptomatic patients. RVI was defined by detection of RV from viral culture. Respiratory viral infectious disease (RVID) was defined as fulfilling both the definition of RVI and the presence of at least one of respiratory symptoms except for fever. In patients with RVID, chest X-ray and/or computed tomography were performed for the diagnosis of upper (URTID) or lower respiratory tract infectious disease (LRTID). ResultsOne hundred and seventy-seven patients (65.3%) developed respiratory symptoms in first 100 days after alloSCT and RVs were detected from 59 patients (24.1%); PIV3 was detected in 49 patients, PIV2 in 3, PIV1 in 1, RSV in 2, FluA in 2, ADV in 1, and mumps virus in 1. There were no culture-positive patients without any symptoms. RVs were detected by PCR and antigen test from 25 culture-negative patients with respiratory symptoms; RSV was detected in 10 patients, PIV3 in 9, FluA in 1, RSV and PIV3 in 1, and PIV3 and ADV in 2. RSV was less detected by viral culture compared to PCR. All patients with RVI developed respiratory symptoms (median days of onset: 15.5 days), and symptoms presented before the detection of RVs in all of them. Radiological findings showed LRTID in 40 patients with RVI. Respiratory symptoms were improved in 39 of patients with RVI and the median duration from onset to cure of their RVID was 26 days (7-115). Although a majority of RVID was self-limited, seven patients (12.1%) died from RV-induced LRTID. Two of them developed interstitial pneumonia without other pathogens, and 5 of them had co-infection with other pathogens; Aspergillus spp. was detected in 1 patient, Pseudomonas aeruginosa in 1, Stenotrophomonas maltophilia in 1, and other RVs in 2 (RSV 1 and ADV 1) only detected by PCR. Six died patients developed RVI-induced LRTID before engraftment. Viral shedding occurred from 1 to 4 weeks (median: 1 week). Phylogenetic analysis of hemagglutinin-neuraminidase genes revealed institutional outbreak of PIV3 in 3 seasons (summer and winter in 2010, summer in 2011). ConclusionThis study showed the high frequency of RV infections in early phase after alloSCT and horizontal dissemination of PIV3 in transplantation unit confirmed by genetical method. Although a majority of RVID was self-limited, patients who developed RVID before engraftment and had concomitant pulmonary infection were sometimes fatal. Thorough prophylactic strategy for respiratory viruses including early precise detection and patient isolation should be necessary to reduce the rate of RVI-induced mortality and to prevent outbreaks by RV. Disclosures:No relevant conflicts of interest to declare.

Fulminant mediastinitis due to extended-spectrum beta-lactamase-producing Klebsiella pneumoniae: atypical presentation and spreading following cardiac surgery

Mediastinitis due to Klebsiella pneumoniae, related to thoracic wall contamination after cardiac surgery, has rarely been described. We aim to report a case of fulminant mediastinitis due to extended-spectrum beta-lactamase-producing K. pneumoniae, secondary to a disseminated concomitant pulmonary infection. The patient remained pauci-symptomatic until clinical manifestations of sepsis acutely appeared.

The strategy for the diagnosis of invasive pulmonary aspergillosis should depend on both the underlying condition and the leukocyte count of patients with hematologic malignancies

AbstractThe identification of the causative organism in invasive pulmonary aspergillosis (IPA) is recommended. We investigated whether a mycologic diagnostic strategy could be optimized based on patient characteristics. Fifty-five patients were enrolled in a prospective study. The presence of Aspergillus in respiratory samples occurred more frequently in non-acute leukemia (AL) patients than in AL patients (P = .0003), and in patients with leukocyte counts more than 100/mm3 (P = .002). In a logistic regression model, these 2 factors appeared to be independent, with an adjusted odds ratio of 7.14 (95% confidence interval, 1.40-36.5) for non-AL patients and an adjusted odds ratio of 6.97 (95% confidence interval, 1.33-36.5) for patients with leukocyte counts more than 100/mm3. A positive mycologic result was also more frequent among patients with lung CT scan signs of airway-invasive disease than among other patients (P = .043). Airway-invasive signs were more frequent among non-AL patients (P = .049), whereas angioinvasive disease was more frequent among both AL patients (P = .01) and patients with leukocyte counts less than 100/mm3 (P = .001). A concomitant pulmonary infection was identified more frequently among non-AL patients (P = .005 vs allogeneic hematopoietic stem cell transplant and P = .048 vs others). Our results suggest that different strategies for diagnosing IPA should be considered based on the underlying condition.

Outcomes of non-HIV-infected patients with Pneumocystis pneumonia and concomitant pulmonary cytomegalovirus infection

The pathogenic effect of concomitant pulmonary cytomegalovirus (CMV) infection on morbidity and mortality of Pneumocystis jirovecii pneumonia (PCP) has been questioned in the case of non-HIV-infected patients. We conducted a retrospective cross-sectional study of patients who were diagnosed with PCP by bronchoalveolar lavage. We compared demographics, clinical characteristics, morbidity, and mortality in non-HIV-infected PCP patients with (n = 31) and without (n = 75) pulmonary CMV infection. Morbidity was assessed by length of hospital stay, admission to the intensive care unit, and use of mechanical ventilation. Mortality was defined as 30-day and 90-day all-cause mortality. Morbidity and mortality did not differ between PCP patients with and without pulmonary CMV infection. In multivariate analysis using the Cox proportional hazard model, haematological malignancy (relative risk (RR) 0.20, 95% confidence interval (95% CI) 0.06-0.71), PCP treatment duration (RR 0.81, 95% CI 0.75-0.88), changing to a second-line regimen due to treatment failure (RR 4.51, 95% CI 1.61-12.64), and mechanical ventilation (RR 17.99, 95% CI 4.83-67.04) were independently associated with 30-day all-cause mortality. Being a solid organ transplant recipient (RR 0.17, 95% CI 0.05-0.56) and the use of mechanical ventilation (RR 6.49, 95% CI 2.84-14.83) were independently associated with 90-day all-cause mortality. However, concomitant pulmonary CMV infection was not associated with either 30-day or 90-day mortality. Our results suggest that concomitant pulmonary CMV infection does not significantly affect the prognosis of PCP, as indicated by morbidity and mortality in non-HIV-infected patients with PCP. Based on this result, we propose that it is not essential to administer an anti-CMV regimen when CMV is co-isolated from the bronchoalveolar lavage in patients with PCP.

Cidofovir Therapy for Adenovirus Pneumonia in an AIDS Patient on HAART: A Case Report

Introduction: Adenovirus infections are associated with significant morbidity and mortality among immunocompromised hosts. Adenovirus pneumonia is a rare and often fatal disease in patients with AIDS. Case Report: We report a case of a 28-year-old woman with advanced HIV/AIDS, who developed pneumonia four weeks after initiation of highly active antiretroviral therapy (HAART). Despite empiric antibiotics, the patient developed worsening hypoxemia and progressive pneumonia on chest x-ray. Culture data from a bronchoalveolar lavage (BAL) was negative for bacteria, fungi, pneumocystis jirovecii, but was positive for adenovirus detected by PCR. After transfer to a tertiary care hospital intensive care unit, a repeat BAL confirmed the presence of adenovirus by immunohistochemical staining. Tissue samples sent for histopathology revealed smudge cells. Serum adenovirus viral load was 1.6 × 105 copies/mL. Intravenous cidofovir, 1 mg/kg/day, was initiated and scheduled three times a week. The patient exhibited remarkable improvement and was discharged to home in stable condition after four doses of cidofovir treatment. Discussion: Prior to our case, the few published accounts of HIV patients with adenovirus pneumonia treated with cidofovir have all resulted in death. Our case is distinct from these cases by the lack of concomitant pulmonary infection and the initiation of HAART prior to presentation. Conclusion: To our knowledge, we present the first case of adenovirus pneumonia in a patient with AIDS successfully treated with cidofovir. Our case suggests that limited and low dose cidofovir may be an efficacious approach to treat adenovirus pneumonia among HIV patients, especially those established on HAART.

Mycological Diagnosis of Invasive Pulmonary Aspergillosis Should Depend on Both the Underlying Condition and the Neutropenia Status of Patients with Hematologic Malignancies

AbstractAbstract 1243 Background.Accurate identification of the causative organism in invasive pulmonary aspergillosis (IPA) is important for both epidemiological reasons and optimal management of patients (pts); therefore, it is now recommended. The most efficient strategy to isolate the fungus, however, is not well-established. The reported mycological yield of bronchoscopy, the most commonly used noninvasive approach, does not exceed 40–60%. In the context of IPA, we investigated whether a mycological diagnostic strategy could be optimized based on pt characteristics. Methods.We used a database of 57 pts with IPA enrolled between May 2005 and February 2007 in a prospective multicenter study primarily designed to determine the performance of several microbiological tools in predicting the outcome of IPA. The study protocol was approved by the ethics committee of Saint-Louis Hospital, and all pts provided informed consent. Statistical methods: Predictive factors of positive microbiological results (cytology and/or culture) were analyzed by Fisher's exact test and multiple regression models. Whenever necessary, groups of pts were compared by Fisher's exact test. Analyses were carried out using R version 2.6.2 statistical software (the R Foundation for Statistical Computing, Vienna, Austria).Pt and IPA characteristics according to the underlying condition. Results.The presence of Aspergillus in respiratory samples was significantly more frequent in non-acute leukemia (AL) pts (83%) than in AL pts (25%) (p=0.0003), and in pts with ANC > 100/mm3 (p=0.0002). In a logistic regression model, these 2 factors appeared independent, with an adjusted OR of 7.27 (95% CI 1.42 to 37.3) for non-AL pts and an adjusted OR of 7.20 (95% CI 1.38 to 37.7) for ANC > 100/mm3. A positive mycological yield was detected in 95% of the non-AL pts with ANC > 100/mm3 vs. 23% of the AL pts with ANC < 100/mm3 (p=0.0002). A positive mycological result was also more frequent among pts with lung CT scan signs of invasive airway disease than among other patients (p=0.026). Furthermore, the CT scan findings were strongly associated with the underlying condition and ANC counts of the pt. In particular, invasive airway signs were significantly more frequent among non-AL pts (p=0.049), whereas angioinvasive disease was significantly more frequent among both AL pts (p=0.01) and patients with ANC < 100/mm3 (p=0.0001). Steroid therapy (yes/no and > or < 1 mg/kg) and previous anti-mold therapy had no significant effect on the results. Notably, a concomitant pulmonary infection was identified with bronchoscopy more frequently among non-AL pts (p=0.0009). Conclusions.We strongly recommend bronchoscopy for a specific diagnosis of aspergillosis among non-AL patients, particularly among allogeneic stem cell transplant recipients. Among AL pts with severe neutropenia, another diagnostic strategy should be considered. Disclosures:No relevant conflicts of interest to declare.

Insidious sinusitis leading to catastrophic cerebral aspergillosis in transplant recipients

Cerebral aspergillosis is an important cause of mortality in organ transplant recipients and is typically associated with concomitant pulmonary infection.1 Herein we describe two patients with insidious Aspergillus sinusitis leading to catastrophic CNS infection. ### Case reports. #### Patient 1. A 56-year-old man with pancreas and kidney transplant was transferred to our tertiary care facility with meningoencephalitis and cerebral infarction. He had a history of new onset headache of 6 weeks with fever. His immunosuppressive regimen consisted of mycophenolate mofetil, prednisone, and tacrolimus with prophylactic sulfamethoxazole/trimethoprim and valganciclovir. He had a temperature of 38.9 °C, opened eyes to voice only but followed commands, and neurologic examination showed neck stiffness, dysarthria, right-sided anisocoria, and a left sided hemiparesis. Empiric antimicrobial therapy was started, including fluconazole. CT showed fluid and membrane thickening within paranasal sinuses. Cranial MRI demonstrated enhancement involving the basilar meninges and sphenoid sinus (figure, A). Diffusion-weighted images demonstrated restricted diffusion in the right pons, right cerebellum, and right caudate head consistent with acute infarction (figure, B). Cerebral angiogram demonstrated narrowing of arteries around the basal cisterns and occlusion of the right superior cerebellar artery, consistent with vasculitis secondary to basal meningitis. Lumbar puncture (LP) revealed CSF leukocytes of 1,200/mm3 (94% neutrophils), protein of 73 g/L, and glucose of 64 mg/dL. Fluconazole was changed to voriconazole. Cultures of CSF remained negative. The serum galactomannan antigen test was normal (0.39 index), …

Clinical and Bronchoscopic Findings in Ugandans with Pulmonary Kaposi's Sarcoma

BackgroundPulmonary Kaposi's sarcoma (PKS) directly affects the life expectancy of those infected and yet the clinical and radiographic features of Kaposi's sarcoma (KS) with pulmonary involvement are nonspecific, which makes diagnosis difficult. In Uganda, pulmonary tuberculosis, which has clinical features that closely resemble those of PKS, also occurs commonly and thus confusion is bound to arise. Bronchoscopy is a recognized diagnostic investigatory modality for PKS. The aim of present study was to identify unique or useful points for the differential diagnosis of PKS and other opportunistic infections.MethodsThe clinical, radiologic, and bronchoscopic findings in thirty-five Ugandan patients (age 20-50, median 32) with PKS were analyzed.ResultsCough and weight loss were most common and occurred in 97.1%, whereas fever occurred in 62.9%, and breathlessness in 57.1%. Thirty-four patients (97.1%) showed mucocutaneous KS, and palatal KS was most frequent and was observed in 74.3%. In addition, 25 patients (71.4%) showed the characteristic endobronchial plaques of KS. The most frequently observed radiographic abnormality was bilateral reticulonodular density. Histological examinations of bronchoscopic biopsies revealed KS in 7 (36.6%) cases. Five PFS patients (25%) also had co-existent tuberculosis.ConclusionsThe majority of patients with PKS showed no specific findings on physical examination, apart from mucocutaneous KS. Our findings indicate that palatal KS may be a strong predictor of PKS. In Uganda, pulmonary tuberculosis may be the most common concomitant pulmonary infection in PKS patients.

Mucormycosis: ten-year experience at a tertiary-care center in Greece.

Presented here are the results of a retrospective analysis of all mucormycoses infections recorded at a tertiary hospital in Greece during the last 10 years. A total of 24 patients were identified, 15 male and 9 female, with ages ranging from 37 to 80 years. Twelve of the patients had soft tissue infections (2 with concomitant pulmonary infections), and 12 had rhinocerebral infections. Transmission could be traced in two cases; to nitroglycerin patches in one patient and to a lemon-tree-thorn scratch in the other. Among the 17 patients who underwent surgery, 11 survived. All seven patients on whom surgery was not performed died. Rapid diagnosis and treatment of mucormycosis are essential for patient survival. The severity of the patient's underlying condition, the degree of immunosuppression, and prompt surgical treatment are the most important factors contributing to the outcome.