Fungal Planet description sheets: 214-280.

Novel species of microfungi described in the present study include the following from South Africa: Cercosporella dolichandrae from Dolichandra unguiscati, Seiridium podocarpi from Podocarpus latifolius, Pseudocercospora parapseudarthriae from Pseudarthria hookeri, Neodevriesia coryneliae from Corynelia uberata on leaves of Afrocarpus falcatus, Ramichloridium eucleae from Euclea undulata and Stachybotrys aloeticola from Aloe sp. (South Africa), as novel member of the Stachybotriaceae fam. nov. Several species were also described from Zambia, and these include Chaetomella zambiensis on unknown Fabaceae, Schizoparme pseudogranati from Terminalia stuhlmannii, Diaporthe isoberliniae from Isoberlinia angolensis, Peyronellaea combreti from Combretum mossambiciensis, Zasmidium rothmanniae and Phaeococcomyces rothmanniae from Rothmannia engleriana, Diaporthe vangueriae from Vangueria infausta and Diaporthe parapterocarpi from Pterocarpus brenanii. Novel species from the Netherlands include: Stagonospora trichophoricola, Keissleriella trichophoricola and Dinemasporium trichophoricola from Trichophorum cespitosum, Phaeosphaeria poae, Keissleriella poagena, Phaeosphaeria poagena, Parastagonospora poagena and Pyrenochaetopsis poae from Poa sp., Septoriella oudemansii from Phragmites australis and Dendryphion europaeum from Hedera helix (Germany) and Heracleum sphondylium (the Netherlands). Novel species from Australia include: Anungitea eucalyptorum from Eucalyptus leaf litter, Beltraniopsis neolitseae and Acrodontium neolitseae from Neolitsea australiensis, Beltraniella endiandrae from Endiandra introrsa, Phaeophleospora parsoniae from Parsonia straminea, Penicillifer martinii from Cynodon dactylon, Ochroconis macrozamiae from Macrozamia leaf litter, Triposporium cycadicola, Circinotrichum cycadis, Cladosporium cycadicola and Acrocalymma cycadis from Cycas spp. Furthermore, Vermiculariopsiella dichapetali is described from Dichapetalum rhodesicum (Botswana), Ophiognomonia acadiensis from Picea rubens (Canada), Setophoma vernoniae from Vernonia polyanthes and Penicillium restingae from soil (Brazil), Pseudolachnella guaviyunis from Myrcianthes pungens (Uruguay) and Pseudocercospora neriicola from Nerium oleander (Italy). Novelties from Spain include: Dendryphiella eucalyptorum from Eucalyptus globulus, Conioscypha minutispora from dead wood, Diplogelasinospora moalensis and Pseudoneurospora canariensis from soil and Inocybe lanatopurpurea from reforested woodland of Pinus spp. Novelties from France include: Kellermania triseptata from Agave angustifolia, Zetiasplozna acaciae from Acacia melanoxylon, Pyrenochaeta pinicola from Pinus sp. and Pseudonectria rusci from Ruscus aculeatus. New species from China include: Dematiocladium celtidicola from Celtis bungeana, Beltrania pseudorhombica, Chaetopsina beijingensis and Toxicocladosporium pini from Pinus spp. and Setophaeosphaeria badalingensis from Hemerocallis fulva. Novel genera of Ascomycetes include Alfaria from Cyperus esculentus (Spain), Rinaldiella from a contaminated human lesion (Georgia), Hyalocladosporiella from Tectona grandis (Brazil), Pseudoacremonium from Saccharum spontaneum and Melnikomyces from leaf litter (Vietnam), Annellosympodiella from Juniperus procera (Ethiopia), Neoceratosperma from Eucalyptus leaves (Thailand), Ramopenidiella from Cycas calcicola (Australia), Cephalotrichiella from air in the Netherlands, Neocamarosporium from Mesembryanthemum sp. and Acervuloseptoria from Ziziphus mucronata (South Africa) and Setophaeosphaeria from Hemerocallis fulva (China). Several novel combinations are also introduced, namely for Phaeosphaeria setosa as Setophaeosphaeria setosa, Phoma heteroderae as Peyronellaea heteroderae and Phyllosticta maydis as Peyronellaea maydis. Morphological and culture characteristics along with ITS DNA barcodes are provided for all taxa.

Primary isolation of Candida species from urine specimens using chromogenic medium.

CHROMagar Candida (CaC) is a chromogenic medium that can be used to detect Candida species, including Candida albicans, Candida krusei, Candida tropicalis, and perhaps Candida glabrata. We evaluated the utility of CaC to detect candiduria in high-risk patients and the potential usefulness of this information in directing initial antifungal therapy in those later identified with candidaemia. CaC was compared in parallel to standard laboratory methods (SM) for the detection of Candida from urine collected from high-risk units and wards. Of 893 samples, Candida was recovered by CaC from 104 compared with 35 using SM. No isolates detected by SM were undetected by CaC. More than one Candida species were recovered by CaC in 19 of the 104 (18.3%); only two mixed cultures were detected by SM. The identification was more rapid with CaC. Five of 69 patients with candiduria detected by CaC developed candidaemia on or after the date of urine culture. SM recovered fungus in only two of these patients. CaC can be used as primary media for the detection of Candida species from urine specimens. Primary isolation by CaC may enable clinicians to make earlier, directed selection of antifungal agents and potentially reduce patient morbidity and mortality.

Use of chromogenic medium in the isolation of yeasts from clinical specimens.

Over a 1 year period 3296 specimens submitted for fungal culture were plated onto routine mycological media (RM) and CHROMagar Candida (CaC) to evaluate the capability of CaC to improve on RM. With RM, cultures producing single yeast isolates were identified from 802 specimens. CaC produced similar results, with 76 % agreement. Of 761 specimens that yielded a single Candida species by RM, 615 (81 %) produced one or more yeast isolates using CaC. Of concern, 132 negative CaC cultures corresponded to specimens that yielded C. albicans alone on RM. When yeasts were recovered, CaC correctly identified 98 % of C. albicans, 93 % of Candida tropicalis, 96 % of Candida glabrata and 100 % of Candida krusei based on typical colours. CaC did potentially improve on RM by detecting yeasts in 91 specimens that yielded none by routine methods. CaC was noted to recover more yeast isolates than RM when mixed cultures were detected. Overall, the role of CaC in improving RM appears limited.

Transient abnormalities in serum bilirubin and lactate dehydrogenase levels following red blood cell transfusions in adults.

BACKGROUND: The effect of transfusion of small amounts of packed red blood cells (PRBC) on serum chemistry values is not known. METHODS: We studied 73 adult patients without evidence of bleeding who received 2-unit PRBC transfusions. In study 1 (n=39), we examined multiple laboratory values pretransfusion and 15 minutes, 1 hour, 2 hours, and 24 hours posttransfusion. In study 2 (n=34), we examined changes in fractionated bilirubin, lactate dehydrogenase, and haptoglobin prior to and 1 hour following the transfusion. RESULTS: Total bilirubin increased from a median pretransfusion baseline of 0.7 mg/dL to 1.4 mg/dL shortly after transfusion (P <0.0005), and then returned to normal 24 hours later. Of the 36 patients with normal pretreatment total bilirubin levels, 17 (47%) became transiently abnormal. The lactate dehydrogenase level increased similarly 15 minutes after transfusion, but returned to baseline 24 hours later. The unconjugated bilirubin level increased from a median baseline pretransfusion value of 0.3 mg/dL to 1.1 mg/dL at 1 hour posttransfusion (P <0.0005). No significant changes were noted in conjugated bilirubin levels or haptoglobin concentration following transfusion. CONCLUSIONS: Transient increases in serum bilirubin and lactate dehydrogenase are seen following transfusion of PRBC. These data should be considered when interpreting laboratory values during the first few hours after a transfusion.

Response of complicated methicillin-resistant Staphylococcus aureus endocarditis to the addition of trovafloxacin.

The newer fluoroquinolones have many properties such as safety, bioavailability, and tissue penetration that make them attractive in the therapy of complicated infections. Unfortunately, the rapid development of resistance by Staphylococcus aureus to ciprofloxacin has dampened interest in these agents for serious staphylococcal infections. A patient with right-sided methicillin-resistant Staphylococcus aureus (MRSA) endocarditis with a complicated clinical course received trovafloxacin in addition to vancomycin and rifampin. He was initially treated with vancomycin, gentamicin, and rifampin for serious MRSA infection, but because of complications, including septic central nervous system emboli, persistent fever, and leukocytosis, gentamicin was stopped and trovafloxacin begun. After this addition the patient improved and completely recovered. In vitro and animal model data show that many newer fluoroquinolones have excellent activity against S. aureus, including MRSA, and are also less likely to induce resistance. Animal models of endocarditis support their efficacy in serious staphylococcal infections.

Persistence of cryptococcomas on neuroimaging.

Three previously normal patients with cryptococcal meningitis had intracranial lesions on computed tomography and magnetic resonance imaging that persisted for >5 years after successful cure with antifungal drugs. Persistence of lesions on neuroimaging should not be misinterpreted as evidence of active cryptococcosis.

Flucytosine monotherapy for cryptococcosis.

Flucytosine (5-FC) monotherapy for cryptococcosis is not advocated because drug resistance emerges during therapy. Reported documentation of this widely accepted belief is surprisingly scarce. Therefore, we reviewed our experience with 5-FC monotherapy for 27 patients treated between 1968 and 1973. Patients were selected on the basis of criteria associated with good prognosis. In this group, 5-FC monotherapy resulted in cure in eight cases and improvement in two. Overall, response was seen in 10 (43%) of 23 evaluable patients. Therapy failed for 13 patients, including 5 who relapsed, 2 who had partial responses, and 6 without response. Resistance was noted to have developed in isolates from six (50%) of 12 patients for whom therapy failed. Although the 57% failure rate associated with 5-FC alone precludes its use as monotherapy, our study did show that this treatment was well tolerated and that failure was not invariably associated with development of resistance.

Development of amphotericin B liposomes bearing antibody specific to Candida albicans.

Liposomes expressing external antibody specific for Candida albicans and encapsulating amphotericin B were developed and characterized in this study. Antibody was first modified by the covalent attachment of palmitic acid residues. Liposomes were produced by reverse-phase evaporation and modified antibody was incorporated into these liposomes via the hydrophobic interaction between the palmitic acid and the phospholipids composing the liposomes. The liposomes were characterized as to the amount of amphotericin B by spectroscopy and for the presence of antibody by protein analysis and secondary immunolabeling by fluorescent and electron microscopic methods. Immunogold labeling showed that the antibody was being expressed externally on the liposomes in the electron microscopic studies and the specificity of these liposomes for C. albicans was observed by secondary immunofluorescence.

Effect of attachment of anticandidal antibody to the surfaces of liposomes encapsulating amphotericin B in the treatment of murine candidiasis.

The effect produced by antibody specific to Candida albicans when attached to liposomes containing amphotericin B was studied in vivo. Liposomal amphotericin B bearing specific immunoglobulin (LAMB-Ab) was compared with the unencapsulated drug (fAMB) and other liposomal amphotericin B formulations in the short-term survival (21 days) of mice with disseminated candidiasis. Both the treatment and prophylaxis of the murine model of candidiasis were explored in these trials. LAMB-Ab increased survival rates in the model more than other liposomal preparations containing amphotericin B. Liposomal amphotericin B compounds as a group prolonged survival over fAMB. Liposomal preparations used for comparison included liposomes with attached nonspecific antibody (LAMB-Ab-), liposomes without antibody (LAMB), and liposomes with unattached specific antibody (LAMB+).

Successful treatment of invasive aspergillosis complicating prolonged treatment-related neutropenia in acute myelogenous leukemia with amphotericin B lipid complex.

Herein we report the successful treatment of invasive aspergillosis with the liposomal amphotericin B (AMB) formulation, Amphotericin B Lipid Complex (ABLC). This investigational compound was employed in a 50-year-old patient with acute myelomonocytic leukemia complicated by prolonged, treatment-induced granulocytopenia and documented Aspergillus flavus sinusitis with signs of disseminated aspergillosis. The patient demonstrated radiographic signs of pulmonary aspergillosis and biochemical signs of hepatic involvement that were resistant to a 23 day course of conventional AMB (Fungizone) therapy. Following therapy with ABLC her fever abated, her chest X-ray findings improved, and her hepatic function tests improved with eventual resolution.

Treatment of hydrocephalus secondary to cryptococcal meningitis by use of shunting.

Hydrocephalus can be associated with increased morbidity and mortality in cryptococcal meningitis if left untreated. Both ventriculoperitoneal and ventriculoatrial shunting have been used in persons with cryptococcosis complicated by hydrocephalus, but the indications for and complications, success, and timing of these interventions are not well known. To this end, we reviewed the clinical courses of 10 non-human immunodeficiency virus-infected patients with hydrocephalus secondary to cryptococcal meningitis who underwent shunting procedures. Nine of 10 patients who underwent shunting had noticeable improvement in dementia and gait. Two patients required late revision of their shunts. Shunt placement in eight patients with acute infection did not disseminate cryptococcal infection into the peritoneum or bloodstream, nor did shunting provide a nidus from which Cryptococcus organisms proved difficult to eradicate. Shunting procedures are a safe and effective therapy for hydrocephalus in patients with cryptococcal meningitis and need not be delayed until patients are mycologically cured.

Evaluation of antibody-bearing liposomal amphotericin B in the treatment of systemic candidiasis in a neutropenic murine model.

The efficacy of liposomal amphotericin B bearing anticandidal antibodies (LAMB-Ab) was investigated in the treatment of systemic candidiasis in a murine model made neutropenic by an intraperitoneal injection of cyclophosphamide. Treatment with a single dose (0.6 mg amphotericin B kg-1 body weight) of LAMB-Ab resulted in an improved survival of neutropenic mice infected with Candida albicans compared to neutropenic mice treated with identical doses of liposomal amphotericin B or free amphotericin B.

Concentrations of airborne Aspergillus compared to the incidence of invasive aspergillosis: lack of correlation.

Air sampling of the rooms and corridors of the oncology wards of the hospital was carried out over a 54-week period to assess the concentration of viable Aspergillus conidia. A. fumigatus and A. flavus were recovered at a mean of 1.83 cfu m-3 air sampled. Individual samplings yielded concentrations of up to 11.6 cfu m-3. Other Aspergillus spp. were recovered at a mean of 2.38 cfu m-3 (maximum 32.6 cfu m-3). Concentration was not correlated with season or hospital ward. Review of autopsy results showed an average of 6.6 cases of aspergillosis annually over a 22-year period. No seasonal variation in case incidence was found. Six cases of invasive aspergillosis were diagnosed on the three cancer wards during the air-sampling period, but no association was seen linking these cases with changes in recovery of airborne Aspergillus. A seasonal pattern was not observed in the overall incidence of aspergillosis cases nor concentrations of airborne conidia.

Treatment of systemic candidiasis in a neutropenic murine model using immunoglobulin G bearing liposomal amphotericin B.

Efficacy of immunoglobulin G (IgG) bearing liposomal amphotericin B (LAMB-IgG), liposomal amphotericin B without IgG (LAMB) or free amphotericin B (fAMB/Fungizone) was investigated in the treatment of systemic candidiasis in a neutropenic mouse model. Treatment with a single dose (0.6 or 0.9 mg amphotericin B per kg body weight) of LAMB-IgG resulted in a significant increase in the survival rate of neutropenic mice infected with 3 x 10(5) cfu of Candida albicans compared to untreated controls, mice injected with IgG, or liposome alone. Survival was also better in neutropenic mice treated with LAMB-IgG than in neutropenic mice treated with the same dose of LAMB or fAMB. Moreover, 65% of all mice survived the infection after treatment with a single dose of 0.6 mg AMB of the LAMB-IgG formulation. Quantitative culture counts of organs showed that both fAMB and LAMB-IgG formulations even at a dose of 0.3 mg AMB/kg, cleared C. albicans from the spleens, livers, and lungs but not from the kidneys. However, a decreased number of C. albicans cells was recovered from the kidneys of mice that survived the infection. Results of the study suggest that LAMB-IgG is more effective than LAMB or fAMB in the therapy of disseminated candidiasis in neutropenic mice.

Opportunistic pulmonary infections with fludarabine in previously treated patients with low-grade lymphoid malignancies: a role for Pneumocystis carinii pneumonia prophylaxis.

The high incidence of opportunistic pulmonary infections in fludarabine-treated patients at Walter Reed Army Medical Center (WRAMC) and in the literature are described. A CancerLit search of fludarabine from June 1983-April 1994 with subsequent cross referencing and a retrospective review of all patients receiving fludarabine at WRAMC was performed. A total of 2,269 patients with low-grade lymphoid malignancies who received 7,547 + cycles of fludarabine were identified from the literature. Seventy-three (3.2%) of these patients developed opportunistic infections. Seventy-one (97%) of these infections occurred in patients who were pretreated with alkylator regimens or corticosteroids. Forty-five (2%) of these were of respiratory origin and associated with a 56% mortality rate. In contrast, 6 of the 21 patients (29%) treated with fludarabine at WRAMC developed opportunistic pulmonary infections which included three Pneumocystis carinii (PCP), one PCP/disseminated Candidiasis, one Mycobacterium avium intracellulare, and one Aspergillus niger pneumonia. These infections developed during and after treatment with fludarabine in alkylator-resistant patients who had received corticosteroids before (n = 6), during (n = 1), or after (n = 4) fludarabine therapy. Lack of PCP prophylaxis was the only significant (P = .018) variable that differentiated patients who developed opportunistic pulmonary infections. Corticosteroid treatment before, during, or after fludarabine treatment in patients with alkylator-resistant, low-grade lymphoid malignancies who have not received PCP prophylaxis is associated with an increased risk of opportunistic pulmonary infections. Aggressive work-up of pulmonary syndromes and PCP prophylaxis in these patients should be considered during and after treatment with fludarabine.

Herpes virus infections occur frequently following treatment with fludarabine: results of a prospective natural history study.

We performed a prospective infectious natural history study of 21 patients with low-grade lymphoproliferative disorders receiving fludarabine as initial (n = 5) or salvage (n = 16) therapy. 12 (57%) of these patients developed herpes zoster (n = 9), herpes simplex I (n = 1) or herpes simplex II (n = 2) infections at a median of 8 (range 1-17) months following initiation of fludarabine, with 75% of these having completed therapy. All patients with herpes zoster developed severe post-herpetic neuralgia. Factors differentiating patients developing these infections included older age and low serum IgG or IgA. Based upon these prospective data, we conclude that herpes virus infections frequently occur following fludarabine treatment, necessitating aggressive patient education and new prophylactic strategies.