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ABSTRACTThe therapeutic efficacy of flucytosine (5FC) monotherapy and the pharmacodynamic index predictive of efficacy were evaluated in a nonneutropenic mouse model of acute invasive aspergillosis. Mice were infected intravenously with an Aspergillus fumigatusisolate (the median MICs of 5FC were 128 μg/ml under the standard condition, 0.5 μg/ml at pH 6.0, and 0.031 μg/ml at pH 5.0) 2 h prior to the start of therapy and were treated for 7 days with different 5FC dosing regimens. The total doses ranged from 50 to 800 mg/kg of body weight/day and were administered at 6-, 12-, and 24-h intervals. The efficacy was assessed by means of survival. The survival rates of the treatment groups ranged from 40 to 90%, while the survival rate of the control group was 20%. The efficacy found depended primarily on the total daily dose. However, the power of our sample size may have been too low to exclude an effect of dose fractionation. The pharmacodynamic index that most strongly correlated with the efficacy was the area under the serum concentration-time curve and MIC ratio (R2= 0.86). We conclude that 5FC monotherapy is efficacious in a murine Aspergillus fumigatusinfection model.

ABSTRACTIn this study, we investigated the pH dependency of the in vitro activities of amphotericin B (AMB) and flucytosine (5FC) against Candidaspp., Cryptococcus neoformans, Aspergillus fumigatus, Rhizopusspp., and Scedosporium prolificansin RPMI 1640 buffered with citrate buffer (pH 4.0, 5.0, 5.4, and 6.0), citrate-phosphate buffer (pH 5.4, 6.0, 6.4, and 7.0), and 3-[N-morpholino]propanesulfonic acid (MOPS) (pH 6.4, 7.0, 7.4, and 7.9). For 5FC, no significant differences were found between MICs obtained with the different buffers, while for AMB, significant differences were found. The MICs obtained with citrate-phosphate buffer were approximately 1 twofold-dilution step higher than the MICs obtained with MOPS. We demonstrated that the in vitro activities of AMB and 5FC against yeast and mold isolates were pH dependent. The in vitro activity of AMB decreased when the pH was lowered, while the in vitro activity of 5FC increased. The effect of the pH on the in vitro activities was dependent not only on the antifungal agent tested but also on the microorganism. For AMB, there was a nonlinear relationship (median r2, 0.864) for Candidaspp., C. neoformans, A. fumigatus, and Rhizopusspp. over the pH range tested. The mean MICs ranged from 0.5 to 2.52 μg/ml at pH 7.0 and from 20.16 to 32 μg/ml at pH 5.0. For S. prolificans, there was no relationship. For 5FC, there was a linear relationship for Candidaspp. (median r2, 0.767) and a nonlinear relationship for C. neoformansand A. fumigatus(median r2, 0.882) over the pH range tested. The mean MIC values ranged from 0.125 to 1,024 μg/ml at pH 7.0 and from 0.02 to 4 μg/ml at pH 5.0. For Rhizopusspp. and S. prolificans, the relationship could not be determined, since the MIC was >1,024 μg/ml over a pH range of 4.0 to 7.9.

ABSTRACTThe in vitro susceptibilities of 21 Aspergillusisolates were tested against three antifungal agents in RPMI 1640 and yeast nitrogen base at pH 5.0 and 7.0 by a broth microdilution format of the NCCLS method. The MICs of amphotericin B and itraconazole were higher, while those of flucytosine were lower, at pH 5.0 than at pH 7.0. The poor correlation between in vitro results and clinical outcome could be due to a difference in pH between the in vitro susceptibility test and at the site of infection.

ABSTRACTCombination therapy of flucytosine (5FC) with other antifungal agents could be of use for the treatment of invasive aspergillosis. However, interpretation of the results of in vitro interactions is problematic. The fractional inhibitory concentration (FIC) index is the most commonly used method, but it has several major drawbacks in characterizing antifungal drug interaction. Alternatively, a response surface approach using the concentration-effect relationship over the whole concentration range instead of just the MIC can be used. We determined the in vitro interactions between amphotericin B (AMB), itraconazole, and 5FC against 21 Aspergillusisolates with a broth microdilution checkerboard method that employs the dye MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide]. FIC indices based on three different MIC endpoints (MIC-0, MIC-1, and MIC-2) and the interaction coefficient alpha were determined, the latter by estimation from the response surface approach described by Greco et al. (W. R. Greco, G. Bravo, and J. C. Parsons, Pharmacol. Rev. 47:331-385, 1995). The value obtained for the FIC index was found to be dependent on the MIC endpoint used and could be either synergistic, indifferent, or antagonistic. The response surface approach gave more consistent results. Of the three combinations tested, the AMB-5FC combination was the most potent in vitro against Aspergillusspp. We conclude that the use of the response surface approach for the interpretation of in vitro interaction studies of antifungals may be helpful in order to predict the nature and intensity of the drug interaction. However, the correlation of these results with clinical outcome remains difficult and needs to be further investigated.

ABSTRACTCombination therapy could be of benefit for the treatment of invasive yeast infections. However, in vitro interaction studies are relatively scarce and the interpretation of the fractional inhibitory concentration (FIC) index can be contradictory due to various definitions used; not all information on the interaction study is used in the index, and different MIC end points exist for different classes of drugs. Fitting an interaction model to the whole response surface and estimation of an interaction coefficient alpha (ICα) would overcome these objections and has the additional advantage that confidence intervals of the interaction are obtained. The efficacy of flucytosine (5FC) in combination with amphotericin B (AB) and fluconazole (FCZ) was studied against 35 yeast isolates in triplicate (Candida albicans[n= 9], Candida glabrata[n= 9], Candida krusei[n= 9], and Cryptococcus neoformans[n= 8]) using a broth microdilution checkerboard method and measuring growth after 48 h by a spectrophotometer. The FIC index and ICα were determined, the latter by estimation from the response surface approach described by Greco et al. (W. R. Greco, G. Bravo, and J. C. Parsons, Pharmacol. Rev. 47:331-385, 1995) by using a computer program developed for that purpose. For the 5FC-FCZ combination, the interactions determined by the ICα generally were in concordance with the interactions determined by the FIC index, but large discrepancies were found between both methods for the 5FC-AB combination. These could mainly be explained by shortcomings in the FIC approach. The in vitro interaction of 5FC-AB demonstrated variable results depending on the tested Candidaisolate. In general, the 5FC-FCZ combination was antagonistic against Candidaspecies, but for some Candidaisolates synergism was found. For C. neoformansthe interaction for both combinations was highly dependent on the tested isolate and the method used. Response surface approach is an alternative method for determining the interaction between antifungal agents. By using this approach, some of the problems encountered with the FIC were overcome.

ABSTRACTAlthough the fractional inhibitory concentration (FIC) index is most frequently used to define or to describe drug interactions, it has some important disadvantages when used for drugs against filamentous fungi. This includes observer bias in the determination of the MIC and no agreement on the endpoints (MIC-0, MIC-1, or MIC-2 [≥95, ≥75, and ≥50% growth inhibition, respectively]) when studying drug combinations. Furthermore, statistical analysis and comparisons are troublesome. The use of a spectrophotometric method to determine the effect of drug combinations yields quantitative data and permits the use of model fits to the whole response surface. We applied the response surface model described by Greco et al. (W. R. Greco, G. Bravo, and J. C. Parsons, Pharmacol. Rev. 47:331-385, 1995) to determine the interaction coefficient alpha (ICα) using a program developed for that purpose and compared the results with FIC indices. The susceptibilities of amphotericin B (AM), itraconazole (IT), and terbinafine (TB) were tested either alone or in combination against 10 IT-susceptible (IT-S) and 5 IT-resistant (IT-R) clinical strains of Aspergillus fumigatususing a modified checkerboard microdilution method that employs the dye MTT [3-(4,5-dimethyl-2-thiazyl)2,5-diphenyl-2H-tetrazolium bromide]. Growth in each well was determined by a spectrophotometer. FIC indices were determined and ICα values were estimated for each organism strain combination, and the latter included error estimates. Depending on the MIC endpoint used, the FIC index ranged from 1.016 to 2.077 for AM-IT, from 0.544 to 1.767 for AM-TB, and from 0.656 to 0.740 for IT-TB for the IT-S strains. For the IT-R strains the FIC index ranged from 0.308 to 1.767 for AM-IT, from 0.512 to 1.646 for AM-TB, and from 0.403 to 0.497 for IT-TB. The results indicate that the degree of interaction is not only determined by the agents themselves but also by the choice of the endpoint. Estimates of the ICα values showed more consistent results. Although the absolute FIC indices were difficult to interpret, there was a good correlation with the results obtained using the ICα values. The combination of AM with either IT or TB was antagonistic in vitro, whereas the combination of IT and TB was synergistic in vitro for both IT-S and IT-R strains. The use of response surface modeling to determine the interaction of drugs against filamentous fungi is promising, and more consistent results are obtained by this method than by using FIC indices.

Acute invasive aspergillosis (IA) is a devastating disease. Early diagnosis allowing an early treatment may improve the prognosis. However, this goal remains difficult to achieve. When diagnosis is confirmed it is often already too late. Galactomannan antigen detection and DNA detection are under clinical evaluation to improve early diagnosis and management of treatment. Despite antifungal treatment mortality rate is still high. Clinical resistance is more often due to the intensity of immunodepression than to high minimum inhibitory concentrations to antifungal agents; however, resistance to itraconazole may occur in rare instances. Beside acute IA, a chronic form of this infection may be seen as chronic necrotizing pulmonary aspergillosis or chronic invasive sinusitis. Other sites of infection have been described. The patients are immunocompetent or present minor alteration of their immunity or of anatomic structure of the infected site. Among patients with solid organ transplantation, lung and liver transplant patients are at the highest risk of developing IA. A high degree of awareness and efforts for an early diagnosis may participate to improve the poor prognosis.

A few systems for determining the saprobic and trophic degree are compared. In determining saprobity the saprobic index according to Dresscher & Van der Mark (1976) appears to be in good agreement with the system developed by Zelinka & Marvan (1961). In defining the trophic degree there is an obvious correspondence between the systems of Hutchinson (1967) and Rawson (1956) and the chemical characterization of the water.

Disseminated candidiasis is a serious infectious complication with a mortality as high as 50%. Standard therapy consists of parenteral amphotericin B which is associated with major side effects and prolonged hospitalization. The aim of the study was to assess the efficacy and safety of fluconazole in an open, noncomparative study. Fluconazole, as a single agent, was given intravenously for the first 3 days at a dose of 200 mg twice daily, followed by 200 mg twice daily orally until resolution of signs and symptoms or evident treatment failure. The study group comprised 24 consecutive patients of whom nine had acute and 15 chronic disseminated candidiasis. A clinical response was achieved in 67% of cases of acute disseminated candidiasis and in 86% of cases of chronic disseminated candidiasis. The median duration of therapy was 15 days and 6 months, respectively. Superinfections with Aspergillus fumigatus developed in five patients who were persistently neutropenic. No drug-related toxicity was registered.

The interaction of Plasmodium falciparum ookinetes with the midgut epithelium of Anopheles stephensi is described by electron microscopy. Plasmodium falciparum ookinetes have been traced during the early stages of invasion and localization beneath the basal lamina of the midgut. It is generally assumed that ookinetes break through two membranes to reach the basal lamina of the midgut epithelium by an intracellular route. In the present study evidence is presented that the ookinete takes an intercellular route in traversing the epithelial layer. Compared to the mode of penetration and intracellular development of sporozoites and merozoites, an intercellular route for penetration of the ookinete is not inconsistent with its further extracellular development.

The aim of this study was to identify retrospectively trends in fungal bloodstream infections in The Netherlands in the period from 1987 to 1995. Results of over 395,000 blood cultures from five Dutch university hospitals were evaluated. Overall, there were more than 12 million patient days of care during the nine-year study period. The rate of candidemia doubled in the study period, reaching an incidence of 0.71 episodes per 10,000 patient days in 1995. The general increase in candidemia was paralleled by an increase in non-Candida albicans bloodstream infections, mainly due toCandida glabrata. However, more than 60% of the infections were caused byCandida albicans. Fluconazoleresistant species such asCandida krusei did not emerge during the study period. The increasing rate of candidemia found in Dutch university hospitals is similar to the trend observed in the USA, but the rate is lower and the increase is less pronounced.

Between March and May 1996 Stenotrophomonas maltophilia was cultured from endotracheal aspirate samples from five preterm infants in a neonatal intensive care unit (NICU). Four infants were superficially colonized, but a fifth died due to S. maltophilia septicaemia. S. maltophilia was cultured from tap water from three outlets in the NICU including one with a previously unnoticed defective sink drain. Water from these outlets was used to wash the preterm infants. Environmental and clinical S. maltophilia isolates yielded identical banding patterns on random arbitrary polymorphic DNA (RAPD) PCR analysis. The outbreak was controlled by reinforcement of hand disinfection, limitation of the use of tap water for hand washing and by using sterile water to wash the preterm infants. We conclude that tap water should not be used for washing preterm infants in the NICU, unless steps are taken to prevent microbial growth in the outlets.

The migration ofPlasmodium falciparum andP. berghei ookinetes through the midgut epithelium inAnopheles stephensi was studied by transmission electron microscopy. With ruthenium red (RR) staining, the results of previous studies were confirmed:P. falciparum ookinetes take an intercellular route through the midgut epithelium. In the same mosquito species, the rodent parasiteP. berghei appeared to take an intracellular position, as previously suggested by other authors. The intra- or intercellular ookinete migration ofP. berghei orP. falciparum, respectively, can perhaps be related to the higher mortality ofP. berghei-infected mosquitoes within the first 2 days of infection. Evidence is presented that oocyst capsule formation begins as early as during the migration of the ookinete. After localization between the epithelial cells and the midgut basal lamina, the rapidly expanding oocyst stretches the overlying layer of the latter at the haemocoelic surface while a new basal lamina is generated between the oocyst and epithelial cell.

The interactions betweenPlasmodium berghei sporozoites and Kupffer cells in rat liver were studied by transmission electron microscopy. Between 10 and 45 min after inoculation, sporozoites were found in the process of entering Kupffer cells and inside phagolysosomes. The sporozoites entered the Kupffer cells by phagocytosis as determined by the presence of pseudopods and local accumulations of aggregated microfilaments and the resulting exclusion of other organelles in the phagocyte cytoplasm beneath the attached parasite. Sporozoites were taken up either with their anterior end first, or backwards. Scanning electron microscopy of in vitro sporozoite Kupffer cell interaction confirmed these observations. It was concluded that sporozoites are taken up in a normal phagocytic way by the Kupffer cells, regardless of their initial place of contact or position. Thirty min after inoculation sporozoites found in phagolysosomes were still morphologically intact but after 45 min we could encounter completely digested sporozoites.

Summary During an outbreak ofSerratia marcescens from May to November 1993 43 strains obtained from 27 ICU patients infected or colonized with multiresistantS. marcescens were genotypically characterized with random amplified polymerase chain reaction (RAPD-PCR)-fingerprinting. In addition, 43 epidemiologically unrelated control isolates were selected. PCR-fingerprinting identified ten different genotypes ofS. marcescens among the outbreak related strains. One predominant genotype was demonstrated in 21/43 isolates of 11/27 patients. A cluster of this genotype was found in seven/eight patients on the cardiosurgical ICU. The epidemiologically unrelated strains all showed different genotypes as compared to the predominant type. This survey proved RAPD-PCR to be a highly discriminatory and reproducible method for epidemiological studies ofS. marcescens strains in nosocomial outbreaks.

Summary Pneumopericardium, the presence of air in the pericardial space, is a rare disorder that is usually caused by trauma. We describe a patient given induction chemotherapy for acute myelogenous leukemia who developed pulmonary aspergillosis that resulted in pericarditis and pneumopericardium. He responded to antifungal treatment and recovered from granulocytopenia, but died early during the next course of chemotherapy. Two other reported cases of pneumopericardium associated with pulmonary aspergillosis are summarized.

Summary Twenty-eight neutropenic (<500 granulocytes/µl) adults with microbiologically or histologically proven systemic mycosis were randomly assigned to receive either amphotericin B alone (0.5 mg/kg/day; n=14) or amphotericin B (0.5 mg/kg/day) plus 5-flucytosine (150 mg/kg/day; n=14) intravenously. Therapy was given for an average duration of 10 days in both groups, amounting to a total dose of amphotericin B of 338 mg and 308 mg, respectively. The mean duration of granulocytopenia was 18 days in the amphotericin B group and 20 days in the combination group. Only two patients treated with amphotericin B alone and three given the combination survived. Adverse events were similiar in both groups with an elevation of the serum creatinine in six cases during the administration of amphotericin B alone and in seven cases treated with the combination. No other serious adverse events were encountered. Treatment with both regimens was disappointing partly because mycosis was too far advanced by the time therapy was begun and neutrophils were recovered in only half the patients.

Aim of this study was to evaluate whether risk factors which predict the development of candidemia may also predict death in ICU patients with candidemia. During an 8-year-period all ICU patients whose blood cultures yieldedCandidaspecies (n=40) were retrospectively evaluated in a case-control fashion. The average incidence ofCandidabloodstream infections was 5.5 per 10,000 patient days, ranging from 2.4 in 1990 to 7.4 in 1994.C. albicanswas the most common pathogen in candidemic patients, but the proportion of non-C. albicansstrains showed an increasing trend during 1989–1993, with a major shift towards non-C. albicansspecies in 1994. The overall mortality of patients with candidemia was 58%. Mortality was highest in the group of patients with multi-organ dysfunction syndrome, especially among those in need of hemodialysis. Risk factors for the development of candidemia, such as age, malignancy, steroid use, i.v. catheterization, and the use of broad-spectrum antibiotics were not correlated with mortality in the ICU patients studied.

Intrahepatocytic transformation in vivo of the rodent malaria sporozoite of Plasmodium berghei, into the young trophic exoerythrocytic tissue stage was studied by immunofluorescence, light- and electron microscopy. The first 20 h of intracellular life were involved entirely in dedifferentiation with limited proliferation of organelles. From about 20 h onwards nuclear division commenced, rough endoplasmic reticulum became markedly expanded, and mitochondria increased in numbers. However, remains of the sporozoite pellicle (i.e., inner membranes and subpellicular microtubules) persisted for at least 28 h, which correlates with the persisting reaction of young exoerythrocytic forms with antisporozoite antibodies. In general, the basic mechanism of transformation resembles that of the ookinete into oocyst and that of the merozoite into erythrocytic trophozoite.

Abstract:  The interval from the time of admission to the emergency room until the administration of antibiotics in patients presenting with a serious infectious disease was analysed. Fifty patients presumptively diagnosed in the emergency room as having a serious infection (respiratory tract, urinary tract, erysipelas, fever with neutropenia or bacteremia) needing immediate empirical antibiotic treatment were enrolled in the study. A median interval from time of admission to administration of antibiotics of 5 hours was determined (range 0.6–13.3 h). The interval was significantly shorter in patients admitted at night than in patients admitted during office hours (3.7 vs. 6.0 h, P<0.05). There was no difference with respect to the presenting features, body temperature, laboratory values at presentation or number of cultures performed. In 41 of the 50 patients blood samples were taken for culture. More than 80% of the patients received an antibiotic chosen in accordance with hospital guidelines. The analysis revealed that the median delay of 5 hours before patients received their initial dose of antibiotic depended on several factors. Attempts to provide optimal antimicrobial therapy should thus concentrate not only on the correct choice and dosage of a drug but also on prompt institution of therapy.

Three cases are reported of hypogammaglobulinemic males with recurrentCampylobacter jejuni septicemia and erysipelas-like cellulitis without diarrhoea. In one patientCampylobacter jejuni grew from skin biopsy specimens. The findings in another patient were strongly suggestive of osteomyelitis caused byCampylobacter jejuni. Since the susceptibility of hypogammaglobulinemic patients to infection withCampylobacter jejuni is probably related to a lack of serum bactericidal activity againstCampylobacter jejuni due to lack of IgM, two patients in whom previous antimicrobial treatment failed were treated with plasma infusions. This regimen supplemented with imipenem resulted in cure of these relapsing infections.Campylobacter jejuni septicemia must be considered in hypogammaglobulinemic patients who present with periodic fever and cellulitis.

Enzyme histochemical methods were performed on sporozoite infected liver tissue of rats in order to gain insight into the nutrition and metabolism of exoerythrocytic forms of Plasmodium berghei. The following enzymes were demonstrated in the hepatocytic stages of the parasites, obtained 41 and 48 h after inoculation of sporozoites: acid phosphatase, cytochrome oxidase, NADH-tetrazolium reductase, succinate dehydrogenase, NAD+ and NADP+ dependent isocitrate dehydrogenase, NADP+-dependent malate dehydrogenase, lactate dehydrogenases, 6-phosphogluconate dehydrogenase and glucose-6-phosphate dehydrogenases and a-glycerol-phosphate dehydrogenase. The results suggest that a conventional Embden-Meyerhoff pathway, pentose phosphate pathway and Krebs' citric acid cycle may in part be present in these exoerythrocytic parasites. Alkaline phosphatase, nucleoside polyphosphatase, 5'nucleotidase. glucose-6-phosphatase, a-glucan phosphorylase, NAD+ dependent malate dehydrogenase, amino-peptidase M and non-specific esterases were not detected by our techniques in the parasite. The enzyme distribution of this intrahepatocytic malaria parasite revealed by histochemistry is compared with the enzyme distribution in the other phases of the parasite's life cycle.

The presence ofCandidain the urine is not considered normal but does not necessarily indicate urinary tract infection. On the other hand, yeasts in urine cultures might be the first symptom of systemic fungal infections. Despite the difficulties that exist, establishment of an accurate diagnosis is important especially in high risk patients because ascending infections may lead to disseminated disease. Amphotericin B bladder irrigation is a common mode of therapy for fungal urinary tract infection, although no specific guidelines exist as to the use of the procedure. The pharmacokinetic parameters posessed by the triazole antifungal agent fluconazole make it a candidate for treating fungal urinary tract infections. Five case reports and 99 patients reported in several small studies were reviewed. As evident from these reports, fluconazole appears to be of value in the treatment of both uncomplicated and complicated fungal urinary tract infections.

Summary A case ofFusobacterium necrophorum bacteremia and multiple brain abscesses in a 6-year-old child following aMycoplasma pneumoniae infection is described. Brain abscess due to this microorganism has only been described in three other cases since 1977. The clinical picture was consistent with postanginal septicemia, with septic metastatic complications normally only seen in teenagers and young adults. The patient was successfully treated with a 2-month course of parenteral penicillin G and metronidazole.

Infections of mammalian malaria parasites start when sporozoites from an infected anopheline mosquito are injected into the bloodstream of the host. The sporozoites enter the hepatocytes and become transformed into exoerythrocytic schizonts. Since the discovery of the primate parasite Plasmodium cynomolgi in monkey hepatocytes1and the rodent parasite Plasmodium berghei in hamster hepatocytes2, the ultrastructure of these stages has been extensively studied both in primate3,4and rodent plasmodia5–10. These observations relate only to the development of the exoerythrocytic schizont 25 h8after sporozoite injection until the final maturation (of P. berghei) 50 h post-inoculation. Recently, we have studied the route of entry of sporozoites across the cellular lining of liver sinusoids and invasion of the liver parenchymal cells11–13by using transmission electron microscopy. The results of these studies in combination with other physiological experiments14–17strongly suggested that the sporozoite was initially harboured by the Kupffer cell, from which the parasite escaped into the neighbouring hepatocyte. The migration of sporozoites from liver sinusoids to hepatocytes can be achieved within a few minutes18. We present here the first ultrastructural observations on the natural transformation of intrahepatocytic sporozoites into exoerythrocytic forms in vivo, using the rodent malaria parasite P. berghei in a laboratory host, the Brown Norway rat. These observations complete the search for the final link in the life cycle of malaria parasites.

Summary Acute Q-fever is a systemic illness which rarely has a fatal outcome. Fatal cases do occur with the chronic form of the disease and associated with endocarditis. This report presents the case of a fatal, acute Q-fever pneumonia in an 11-year-old patient with chronic granulomatous disease. Complement fixation antibody titer rose to 1:1,024 with positive IgM in immunofluorescence. Giemsa stained lung sections and indirect immunofluorescence demonstrated the microorganisms in the tissues. TheCoxiella burnetii infection was probably contracted during a holiday trip to rural France. Despite the fact that the patient received a variety of antimicrobial agents with broad spectrum activity against bacteria and fungi, coverage for Q-fever, i.e. chloramphenicol or tetracyclines, was not included.

Summary Group G streptococci can cause serious infections in patients with predisposing factors. Involvement of the eye has rarely been reported in patients without ocular history. Two cases of group G streptococcal endocarditis which presented with an endogenous endophthalmitis are reported. Topical and systemic antimicrobial therapy resulted in recovery, but visual outcome was poor.

Acute invasive aspergillosis (IA) is a devastating disease. Early diagnosis allowing an early treatment may improve the prognosis. However, this goal remains difficult to achieve. When diagnosis is confirmed it is often already too late. Galactomannan antigen detection and DNA detection are under clinical evaluation to improve early diagnosis and management of treatment. Despite antifungal treatment mortality rate is still high. Clinical resistance is more often due to the intensity of immunodepression than to high minimum inhibitory concentrations to antifungal agents; however, resistance to itraconazole may occur in rare instances. Beside acute IA, a chronic form of this infection may be seen as chronic necrotizing pulmonary aspergillosis or chronic invasive sinusitis. Other sites of infection have been described. The patients are immunocompetent or present minor alteration of their immunity or of anatomic structure of the infected site. Among patients with solid organ transplantation, lung and liver transplant patients are at the highest risk of developing IA. A high degree of awareness and efforts for an early diagnosis may participate to improve the poor prognosis.