Non-neutropenic Hosts Research Articles

361. Think Fungus! – Clinical profile, Risk factors and Diagnostic Utility of Galactomannan in diagnosis of Invasive Aspergillosis in Non-Neutropenic patients – A Prospective Study from India

Abstract Background Invasive aspergillosis(IA) is known to occur in immunocompromised patients including neutropenic patients. But there has been a trend of increasing cases in non-neutropenic host with the emergence of newer risk factors like DM, cirrhosis etc. The aim of this study was to evaluate the clinical features & risk factors of IA in non-neutropenic patients & to look at the clinical utility of galactomannan in diagnosis of IA. Methods This was a prospective observational study which included the suspected cases of IA, based on the clinical & radiological criteria. Patients with haematological & solid organ malignancy were excluded. In patients with suspected Invasive pulmonary aspergillosis (IPA), serum & BAL, while in patients with suspected CNS IA CSF & serum samples were sent for galactomannan analysis (Platelia ELISA). The clinical features, risk factors, outcomes were analysed. Results We screened 243 patients with suspected IA, of which 49 non-neutropenic patients with IA (16 Proven & 33 Probable cases) were included. The mean age was 47.8 years. Of all IA cases 69.5% (n=34) were IPA, 20.4% (n=10) were CNS aspergillosis & 10.2% (n=5) showed disseminated form of IA. The common symptoms included Fever (71.4%), cough (71.3%), expectoration (44.7%) & dyspnoea (59.1%) in IPA, while in CNS aspergillosis, presented with fever (73.3%), altered sensorium (53%).The predominant risk factor included previous TB, DM, COVID-19. The radiological manifestations in IPA included the typical cavity (40.4%, n=17), Centrilobular nodules with tree in bud appearance in 56.5% (n=23). The CNS aspergillosis was associated with ring enhancing lesion (41.6%, n=5) with leptomeningeal enhancement (50%, n=6), while cerebral abscess was seen in 16.6% (n=2) patients. The positivity of galactomannan were 24.4%, 91.3% & 87.5% in serum, BALF & CSF respectively. Culture positivity & Direct smear positivity was 18.3% & 28.5% respectively. The overall mortality was 20.4%. Complete response in 3 months follow-up period was seen in 69.3% patients. Conclusion The clinical manifestations of IA in non-neutropenic are diverse & nonspecific. Also, culture & direct microscopy lack sensitivity, hence diagnostic markers like Galactomannan can be used for early diagnosis of IA in patients with newer emerging risk factors. Disclosures All Authors: No reported disclosures.

P499 A cross-sectional observational to assess the role of Bronchoalveolar lavage fluid galactomannan in the diagnosis of invasive pulmonary aspergillosis in non-neutropenic patients

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PMObjective: This study was done to assess the role of Bronchoalveolar lavage fluid (BALF) galactomannan (GM) in the diagnosis of invasive pulmonary aspergillosis (IPA) in non-neutropenic patients and to determine the optimal cut-off value of BALF GM for diagnosing IPA in non-neutropenic hosts.MethodsWe conducted a cross-sectional observational study on 96 non-neutropenic patients of age > 18 years with suspected pulmonary infections of fungal etiology. A detailed history of predisposing conditions was obtained and routine laboratory investigations with chest computerized (CT) tomography were performed. Fiberoptic bronchoscopy under local anesthesia and sedation was done using a video bronchoscope. Bronchoalveolar lavage was done from the segment or lobe of interest instilling 60-100 ml of saline withdrawn under low pressure and the sample was tested for a battery of investigations; fungal KOH smear; fungal culture; GM by Platelia Aspergillus enzyme immunoassay; and others required for diagnosis. A protected brush specimen and transbronchial lung biopsy were done wherever feasible. The yield from the BALF GM assay was compared with diagnosis based on definitions given by EORTC/MSG excluding host factors. Patients were classified into three groups namely non-IPA, probable IPA, and proven IPA. For statistical analysis, probable and proven IPA were taken as one group i.e., the IPA group. Mann-Whitney test and Chi-Square test along with Fisher's exact test were performed for inter-group comparison between quantitative and qualitative variables respectively. The receiver operator characteristic curve was used to establish a cut-off point of BALF GM and Serum GM for predicting IPA. Sensitivity, specificity, PPV, and NPV were calculated. The McNemar test was used for the comparison of sensitivity and specificity. Inter-rater kappa agreement was used to find the strength of agreement of BALF GM, BALF culture, and BALF DM.ResultsOut of 96, 1 was diagnosed with proven IPA, 34 were probable IPA cases and 61 were not IPA cases. Chronic kidney disease (CKD) as a risk factor was more common in IPA cases compared to non-IPA cases (25.7% vs. 8.2%, P-value .019). Chest CT showed cavity in a significant number of IPA patients compared to non-IPA cases (60% vs. 29.5%, P-value .003). BALF direct microscopy, culture, and serum GM had sensitivities < 60% but specificities close to 95%. BALF GM showed promising results with a sensitivity of 88.5% and specificity of 85.7% at cutoff value of 0.8.See Figures below.Conclusions: Our study highlights the magnitude of IPA in non-neutropenic hosts with unconventional risk factors like CKD, diabetes, and the need for increased vigilance for diagnosis of IPA in such patients. We suggest a lower cut-off value of BALF GM against 1 as in EORTC/MSG criteria and consider CKD as one of the risk factors for IPA.

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.

Characterization of the putative polysaccharide synthase CpsA and its effects on the virulence of the human pathogen Aspergillus fumigatus.

The fungus Aspergillus fumigatus is a ubiquitous opportunistic human pathogen capable of causing a life-threatening disease called invasive aspergillosis, or IA, with an associated 40–90% mortality rate in immunocompromised patients. Of the approximately 250 species known in the genus Aspergillus, A. fumigatus is responsible for up to 90% of IA infections. This study focuses on examining the role of the putative polysaccharide synthase cpsA gene in A. fumigatus virulence. Additionally, we evaluated its role in cellular processes that influence invasion and colonization of host tissue. Importantly, our results support that cpsA is indispensable for virulence in A. fumigatus infection of non-neutropenic hosts. Our study revealed that cpsA affects growth and sporulation in this fungus. Absence of cpsA resulted in a drastic reduction in conidiation, and forced overexpression of cpsA produced partially fluffy colonies with low sporulation levels, suggesting that wild-type cpsA expression levels are required for proper conidiation in this fungus. This study also showed that cpsA is necessary for normal cell wall integrity and composition. Furthermore, both deletion and overexpression of cpsA resulted in a reduction in the ability of A. fumigatus to adhere to surfaces, and caused increased sensitivity to oxidative stress. Interestingly, metabolomics analysis indicated that cpsA affects A. fumigatus secondary metabolism. Forced overexpression of cpsA resulted in a statistically significant difference in the production of fumigaclavine A, fumigaclavine B, fumigaclavine C, verruculogen TR-2, and tryprostatin A.

Functional convergence of gliP and aspf1 in Aspergillus fumigatus pathogenicity

ABSTRACT Gliotoxin contributes to the virulence of the fungus Aspergillus fumigatus in non-neutropenic mice that are immunosuppressed with corticosteroids. To investigate how the absence of gliotoxin affects both the fungus and the host, we used a nanoString nCounter to analyze their transcriptional responses during pulmonary infection of a non-neutropenic host with a gliotoxin-deficient ΔgliP mutant. We found that the ΔgliP mutation led to increased expression of aspf1, which specifies a secreted ribotoxin. Prior studies have shown that aspf1, like gliP, is not required for virulence in a neutropenic infection model, but its role in a non-neutropenic infection model has not been fully investigated. To investigate the functional significance of this up-regulation of aspf1, a Δaspf1 single mutant and a Δaspf1 ΔgliP double mutant were constructed. Both Δaspf1 and ΔgliP single mutants had reduced lethality in non-neutropenic mice, and a Δaspf1 ΔgliP double mutant had a greater reduction in lethality than either single mutant. Analysis of mice infected with these mutants indicated that the presence of gliP is associated with massive apoptosis of leukocytes at the foci of infection and inhibition of chemokine production. Also, the combination of gliP and aspf1 is associated with suppression of CXCL1 chemokine expression. Thus, aspf1 contributes to A. fumigatus pathogenicity in non-neutropenic mice and its up-regulation in the ΔgliP mutant may partially compensate for the absence of gliotoxin. Abbreviations:PAS: periodic acid-Schiff; PBS: phosphate buffered saline; ROS: reactive oxygen species; TUNEL: terminal deoxynucleotidyl transferase dUTP nick-end labeling

P. aeruginosa blood stream infection isolates: A “full house” of virulence genes in isolates associated with rapid patient death and patient survival

We have recently characterised the epidemiology of P. aeruginosa blood stream infection (BSI) in a large retrospective multicentre cohort study [1]. Utilising corresponding patient BSI isolates we aimed to characterise the genotypic virulence profile of the P. aeruginosa isolates that were associated with rapid death in the non-neutropenic host. Five P. aeruginosa BSI episodes were identified from a larger cohort of P. aeruginosa BSI episodes previously described by McCarthy et al. [1]. The genotypic profile of another 5 isolates from this cohort in whom the non-neutropenic host had survived one year post the BSI was also analysed for comparison. These isolates underwent Illumina whole genome sequencing, de novo assembly and annotation. A comprehensive suite of virulence genes was collated from the Pseudomonas Genome Database (http://www.pseudomonas.com/) and were searched by BLAST based analysis in assemblies of all BSI isolates [2]. There was extensive conservation of virulence genes across all of the BSI isolates studied. The exoU gene was found in two isolates from patients who died rapidly and in one isolate from a patient that survived one year post BSI. The higA and higB genes were detected in all isolates. The exlA gene was not detected in any of the isolates studied. These findings suggest that to cause a BSI that it is only the virulent P. aeruginosa isolate that succeeds. The virulence gene profile seen was independent of patient outcome. Further phenotypic correlation is required to determine if there is any difference in genotypic expression by the BSI isolates that were associated with rapid death of the host and those BSI isolates associated with host survival at one year.

Sustained Clostridium tertium Bacteremia in a Nonneutropenic Patient

Abstract We report a case of sustained Clostridium tertium bacteremia mimicking an endovascular infection in a nonneutropenic patient with metastatic pancreatic neuroendocrine cancer. Clostridium tertium infection has been increasingly recognized in immunocompromised patients. The significance of this organism in nonneutropenic host, however, is unclear. The diagnosis and treatment can be challenging owing to morphology and antibiotic resistance patterns. Newer rapid identification testing with mass spectrometry enables for early diagnosis and treatment. We discuss the clinical significance of C. tertium as an emerging pathogen with review of the literature.

In silico modeling of spore inhalation reveals fungal persistence following low dose exposure.

The human lung is constantly exposed to spores of the environmental mould Aspergillus fumigatus, a major opportunistic pathogen. The spectrum of resultant disease is the outcome of complex host-pathogen interactions, an integrated, quantitative understanding of which lies beyond the ethical and technical reach permitted by animal studies. Here we construct a mathematical model of spore inhalation and clearance by concerted actions of macrophages and neutrophils, and use it to derive a mechanistic understanding of pathogen clearance by the healthy, immunocompetent host. In particular, we investigated the impact of inoculum size upon outcomes of single-dose fungal exposure by simulated titrations of inoculation dose, from 106 to 102 spores. Simulated low-dose (102) spore exposure, an everyday occurrence for humans, revealed a counter-intuitive prediction of fungal persistence (>3 days). The model predictions were reflected in the short-term dynamics of experimental murine exposure to fungal spores, thereby highlighting the potential of mathematical modelling for studying relevant behaviours in experimental models of fungal disease. Our model suggests that infectious outcomes can be highly dependent upon short-term dynamics of fungal exposure, which may govern occurrence of cyclic or persistent subclinical fungal colonisation of the lung following low dose spore inhalation in non-neutropenic hosts.

&amp;lt;i&amp;gt;Rothiamucilaginosa&amp;lt;/i&amp;gt; life threatening infections in non-neutropenic hosts

Rothiamucilaginosa, previously known as Stomatococcus mucilaginous, resides in the oral cavity and respiratory tract as part of the normal flora [1]. It is a gram-positive, cocus-shaped bacterium. The bacterium is considered an emerging opportunistic pathogen in patients with chronic immunosuppressive diseases. Most of these reports were described in severe neutropenia or hematological cancer patients but less frequently in immune-competent hosts. We report two cases of endocarditis and meningitis due to R. mucilaginosain non-neutropenic hosts.

Neutropenia Enhances Lung Dendritic Cell Recruitment in Response to Aspergillus via a Cytokine-to-Chemokine Amplification Loop

Current understanding of specific defense mechanisms in the context of neutropenic infections is limited. It has previously been reported that invasive aspergillosis, a prototypic opportunistic infection in neutropenic hosts, is associated with marked accumulation of inflammatory dendritic cells (DCs) in the lungs. Given recent data indicating that neutrophils can modulate immune responses independent of their direct microbial killing, we hypothesized that neutropenia impacts the host response to Aspergillus by determining the migration and phenotype of lung DCs. Inflammatory DCs, but not other DC subsets, were found to accumulate in the lungs of neutropenic hosts challenged with killed or live-attenuated Aspergillus as compared with nonneutropenic hosts, indicating that the accumulation was independent of neutrophil microbicidal activity. The mechanism of this accumulation in neutropenic hosts was found to be augmented influx of DCs, or their precursors, from the blood to the lungs. This effect was attributable to greatly elevated lung TNF expression in neutropenic as compared with nonneutropenic animals. This resulted in greater lung expression of the chemokine ligands CCL2 and CCL20, which, in turn, mediated enhanced recruitment of TNF-producing inflammatory DCs, resulting in a positive feedback cycle. Finally, in the context of neutropenic invasive aspergillosis, depletion of DCs resulted in impaired fungal clearance, indicating that this mechanism is protective for the host. These observations identify what we believe is a novel defense mechanism in invasive aspergillosis that is the result of alterations in DC traffic and phenotype and is specific to neutropenic hosts.

Invasive Aspergillosis in Solid Organ Transplant Recipients

This chapter discusses the current status and evolving trends in the epidemiology, risk factors, diagnostic laboratory assays, and the approach to antifungal prophylaxis and treatment of invasive aspergillosis in Solid Organ Transplant (SOT) recipients. Most invasive fungal infections in these high-risk patients occur within the first month posttransplant; the median time to onset of invasive aspergillosis after renal replacement therapy and retransplantation was 13 and 28 days, respectively, in one study. Other factors associated with invasive aspergillosis in liver transplant recipients include transplantation for fulminate hepatic failure, cytomegalovirus (CMV) infection, and prolonged intensive care unit stay. A retrospective survey documented invasive pulmonary aspergillosis in 7.5% (19/251) of lung transplant recipients, of whom 47% (9/19) had disseminated aspergillosis. In a survey of antifungal prophylactic strategies in lung transplant units in the United States, aerosolized amphotericin B was the most frequently employed antifungal prophylactic agent. In order of preference, the prophylactic agents used in lung transplant centers in this study were inhaled amphotericin B (61%), itraconazole (46%), parenteral amphotericin formulations (25%), and fluconazole (21%); many centers used more than one agent. Preemptive therapy, where antifungal prophylaxis is directed towards lung transplant recipients colonized with Aspergillus spp. immediately before or within 6 to 9 months after transplantation, is another approach to the prevention of invasive aspergillosis in lung transplant recipients.

New Developments in Antimicrobial Use in Sepsis

Over the past decade, trends in antimicrobial resistance, epidemiology, and drug development have occurred that affect both the empiric and definite selection of antimicrobials in the septic patient. The rapid spread of highly pathogenic community-associated methicillin resistant Staph aureus (MRSA) requires clinicians to consider the inclusion of empiric coverage for MRSA even in community-acquired sepsis. Moreover, vancomycin appears to be losing its effectiveness, and while a number of new agents with broad gram positive activity have been licensed, none have emerged as clearly superior. An alarming increase in the number of hospital-acquired infections due to multi-drug resistant gram negative bacteria has also occurred, and few new gram negative drugs are in development. Clinicians, faced with Pseudomonas aeruginosa or Acinetobacter baumanii isolates resistant to all commonly used drugs, must resort to toxic older drugs such as colistin or therapy combining drugs not effective as monotherapy. Based on a desire to limit overall antimicrobial use, a re-evaluation of older data in both the neutropenic and non-neutropenic host has called into question the common practice of using combination therapy for some gram negative infections. An emerging consensus advocates emphasizing local unit specific antimicrobial sensitivity data in selecting empiric therapy and determining if combination therapy is required. New antifungal drugs and a better understanding of the risk factors for infection with Candida spp. has altered the approach to empiric and definitive treatment of Candida infections in the septic patient.

Granulocyte-Colony Stimulating Factor (G-CSF) as an adjunct to antibiotics in the treatment of pneumonia in adults

Granulocyte colony stimulating factor (G-CSF) is a naturally-occurring cytokine that has been shown to increase neutrophil function and number. Exogenous administration of recombinant G-CSF (filgrastim, pegfilgrastim or lenograstim) has found extensive use in the treatment of febrile neutropenia, but its role in the treatment of infection in non-neutropenic hosts is less well defined. We explored the role of G-CSF as an adjunct to antibiotics in the treatment of pneumonia in non-neutropenic adults. For this updated review we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4, 2006); MEDLINE (1950 to January 2007); EMBASE (1988 to January 2007); and online databases of clinical trials (www.controlled-trials.com, updated 10 November, 2006). We considered randomized controlled trials (RCTs) which included hospitalized adult patients with either community-acquired pneumonia or hospital-acquired pneumonia. Two review authors independently extracted data and assessed trial quality. The primary outcome measure was 28-day mortality. Secondary outcome measures included other markers of mortality as well as markers of adverse events, including organ dysfunction. An assessment of methodological quality was made for each study. Six studies with a total of 2018 people were identified. G-CSF use appeared to be safe with no increase in the incidence of total serious adverse events (pooled odds ratio (OR) 0.91; 95% confidence interval (CI): 0.73 to 1.14) or organ dysfunction. However, the use of G-CSF was not associated with improved 28-day mortality (pooled OR 0.81; 95% CI: 0.52 to 1.27). There is no current evidence supporting the routine use of G-CSF in the treatment of pneumonia. Studies in which G-CSF is administered prophylactically or earlier in therapy may be of interest.

Effect of adjunctive treatment with gamma interferon against Pseudomonas aeruginosa pneumonia in neutropenic and non-neutropenic hosts

To evaluate the adjunctive effect of interferon-gamma (IFN-γ) in treatment of Pseudomonas aeruginosa pneumonia, neutropenic and non-neutropenic mice received LD 100 of the organism intratracheally, followed by subcutaneous administration of IFN-γ, ceftazidime (TAZ) or a combination of both agents 2 h post-inoculation. Treatment with IFN-γ alone showed no significant increase in survival when compared with control. Addition of IFN-γ to TAZ resulted in no significant change in survival compared with TAZ alone. Survival in TAZ and TAZ + IFN-γ groups, was significantly higher than in control and IFN-γ groups. This suggests that adjunctive treatment with IFN-γ in combination with ceftazidime may not be more beneficial than the antibiotic alone when managing acute P. aeruginosa pneumonia in both immunocompromised and immunocompetent hosts.

Adjunctive efficacy of granulocyte colony-stimulating factor on treatment of Pseudomonas aeruginosa pneumonia in neutropenic and non-neutropenic hosts.

Granulocyte colony-stimulating factor (G-CSF) stimulates proliferation of neutrophils and enhances their phagocytic and microcidal activity. Increasing resistance to existing antibacterials and the dearth of new alternatives have complicated the treatment of Gram-negative infections. The aim of this study was to evaluate the efficacy of G-CSF in the treatment of Pseudomonas aeruginosa pneumonia when administered in combination with ceftazidime in both neutropenic and non-neutropenic hosts. A group of mice were rendered neutropenic with cyclophosphamide. Pneumonia was induced by intratracheal instillation of approximately 5 x 10(7) cfu/mL and approximately 5 x 10(9) cfu/mL (LD(100)) of the organism to neutropenic and non-neutropenic mice, respectively. Two hours after inoculation, the mice received normal saline and 5% dextrose, G-CSF (300 micro g/kg per day x 3 days), ceftazidime (2000 mg/kg x 2 doses) or a combination of G-CSF and ceftazidime. Survival was monitored at different time points for 5 days. Treatment with G-CSF showed a dose-dependent increase in survival from 50 to 300 micro g/kg. In neutropenic mice, survival was markedly better in the G-CSF + ceftazidime group compared with controls (P = 0.0001), G-CSF (P = 0.0002) or ceftazidime (P = 0.0172). In non-neutropenic mice, survival in the G-CSF + ceftazidime group (20%) was significantly higher than in the control and G-CSF groups (P = 0.0001) but not significantly higher than ceftazidime alone (9%) (P > 0.05). G-CSF administered in combination with antibiotic after onset of severe P. aeruginosa pneumonia may improve therapeutic outcome and this suggests a new treatment option in the management of pneumonia especially in neutropenic patients.

Single versus combined antibiotic therapy for gram-negative infections.

To evaluate the available clinical data regarding single versus combination antimicrobial therapy for treatment of gram-negative infections, focusing on the more recent data in predominantly nonneutropenic hosts. In vitro and in vivo data regarding various antimicrobial combinations are also discussed. Clinical trials, review articles, and meta-analyses were identified from a MEDLINE search (1960-July 2003). Special attention was given to clinical outcome trials performed since 1989. Search terms included gram-negative infections, drug synergism, Pseudomonas aeruginosa, monotherapy, combination therapy, carbapenems, beta-lactams, cefepime, aminoglycosides, and fluoroquinolones. Although most of the studies were not randomized, double-blind, or controlled, the most recent literature indicates that monotherapy with agents that are active against isolated organisms, including P. aeruginosa, may be appropriate for most patients. Efficacy outcomes, including mortality, did not significantly differ in most studies comparing single and combination therapies. Some trials suggest that combination therapy may be preferred in neutropenic patients and those with pseudomonal infections. Hospitalized patients with gram-negative infections are often treated with combination antimicrobial agents; however, some of the recently available data, although limited, suggest that administration of monotherapy is a feasible alternative in certain patient populations.

Deep Candida infections in the neutropenic and non-neutropenic host: an ISHAM symposium

Deep Candida infections in the neutropenic and non-neutropenic host: an ISHAM symposium

Deep Candida infections in the neutropenic and non-neutropenic host: an ISHAM symposium

Deep Candida infections in the neutropenic and non-neutropenic host: an ISHAM symposium

DeepCandidainfections in the neutropenic and non-neutropenic host: an ISHAM symposium

Deep<i>Candida</i>infections in the neutropenic and non-neutropenic host: an ISHAM symposium

Deep Candida infections in the neutropenic and non-neutropenic host: an ISHAM symposium

A symposium was held on May 8, 2000 to discuss the management of deep infections with Candida species. Among the findings discussed were the following. Candiduria is most often benign, though it occurs in patients with serious underlying diseases. Candida species are now the fourth most common cause of nosocomial bloodstream infections, usually arising from an intravenous catheter. Candida albicans represents only 50-60% of the isolates. There has been no change in the frequency of fluconazole resistance in C. albicans but some of the other species now being isolated from blood are constitutively more resistant to this drug. Nevertheless, for most non-neutropenic patients with candidemia, fluconazole is a reasonable choice for initial therapy. In the neutropenic patient, candidemia is now uncommon. Deep candida infections in neutropenic patients are usually being treated empirically with an amphotericin B formulation. Hepatosplenic candidiasis is usually detected only after recovery from neutropenia but can be suspected by imaging techniques. Improved diagnostic techniques for deep candidiasis in the neutropenic patient remain a critical requirement.