Psoas abscess: report of a series and review of the literature.

We describe a series of twelve patients with a psoas abscess seen in a three-year period in a university hospital and a large teaching hospital in the Netherlands. In our series, five of the 12 patients had a primary psoas abscess. The predisposing conditions were intravenous drug use, diabetes mellitus, prostate carcinoma and haematoma in the psoas muscle in a patient with haemophilia A. Seven of the 12 patients had a secondary psoas abscess. Five cases were due to vertebral osteomyelitis including two cases of tuberculosis. In the other two cases it was due to colitis and urinary tract infection. It is remarkable that in our series there was only one patient with a psoas abscess secondary to a disease of the digestive tract, while this is the most common cause of a secondary psoas abscess in the literature. There were two cases of tuberculosis which is an emerging disease again.

Prevention of infections in hyposplenic and asplenic patients: an update.

Patients with functional or anatomic asplenia are at a significantly increased risk of overwhelming infection, particularly involving the encapsulated bacteria Streptococcus pneumoniae and Haemophilus influenzae. The risk is highest in infants and young children, but adults also have an increased risk of infection. Preventive strategies are very important and fall into three major categories: immunoprophylaxis, antibiotic prophylaxis and education. Studies have shown that many asplenic patients are unaware of their increased risk for serious infection and the appropriate health precautions that should be undertaken. In this article we emphasise the need for preventive measures in hyposplenic and asplenic patients. We discuss the value of newly developed conjugate vaccines and the need for revaccination. Finally we draw up a recommendation for the preventive management in functional and anatomical asplenic patients.

Cerebrospinal fluid leakage during transsphenoidal surgery: postoperative external lumbar drainage reduces the risk for meningitis.

Postoperative meningitis is a well known complication of transsphenoidal surgery (TSS). The objective of this study was to evaluate whether postoperative external cerobrospinal fluid (CSF) drainage in case of intraoperative CSF-leakage, reduces the risk of postoperative meningitis. We retrospectively reviewed a series of 278 consecutive transsphenoidal operations. In all operations with intraoperative CSF leakage, an external lumbar drain (ELD) was inserted directly postoperatively, and removed after at least 5 days. The incidence of postoperative meningitis was compared with that in a previously studied series of 228 consecutive transsphenoidal operations, without insertion of an ELD in cases with intraoperative CSF leakage. In the present series, postoperative meningitis occurred in 2/278 (0.7%) operations, compared to 7/228 (3.1%) operations in the previous study period (P < 0.05). Intraoperative CSF leakage was noted in 70/278 (25.2%) operations. All these patients received an ELD immediately after surgery for at least 5 days. There were no reported complications of ELD insertion. In the present series, 1 of 70 (1.4%) patients with intraoperative CSF leakage developed meningitis, compared to 3 of 22 (13.6%) patients in the previous study (P < 0.05). The present report on 278 consecutive transsphenoidal operations shows that the routine insertion of an ELD in patients in whom intraoperative CSF leakage is observed significantly reduces the incidence of postoperative meningitis. Possibly, diversion of CSF prevents the formation of a CSF fistula and thereby the risk of infection. The role of prophylactic antibiotic treatment in patients with CSF rhinorrhea after TSS remains to be established.

[Treatment adherence amongst HIV-infected patients in Rotterdam: poorer prognosis independent of nationality in heterosexual infected patients, intravenous drug users, Negroid and Latin-American patients]. / Therapietrouw onder HIV-geïnfecteerden in Rotterdam: onafhankelijk van nationaliteit slechter bij heteroseksueel besmette patiënten, intraveneuzedruggebruikers, negroïde en Latijns-Amerikaanse patiënten.

OBJECTIVE: To assess adherence to antiretroviral therapy (ART) in Dutch and non-Dutch HIV-infected patients. DESIGN: Observational, cross-sectional study. METHODS: Consecutive HIV-infected patients taking ART and visiting the internal medicine outpatients' clinic at the Rotterdam Dijkzigt University Hospital between 1 February until 30 April 2001 were interviewed by a multilingual interviewer using a standard questionnaire. Classification of adherence was based on the interview data. Multivariate analysis was used to determine independent predictors of adherence. Nationality was defined as 'Dutch' if the person was born in the Netherlands, and otherwise as 'non-Dutch'. RESULTS: The 203 patients included in this study comprised 131 men and 69 women with an average age of 42 years. There were no data available on treatment adherence for 3 of the patients. Of the 81 Dutch patients, 60 (74%) adhered to the treatment compared with 68 (57%) of the 119 non-Dutch patients. However, after correction for sex, risk group, race and duration of treatment, there was no difference in treatment adherence between these two groups (OR: 0.6; 95% CI: 0.2-1.9). Failure to adhere to treatment was seen most frequently in the 109 heterosexually infected patients (OR: 2.6; 0.98-6.7), the 22 intravenous drug users (OR: 3.3; 1.04-10.1), as well as in the group of Negroid patients (OR: 3.5; 1.1-11.3) and Latin-American patients (OR: 8.5; 1.7-42.7).

Rapid emergence of ciprofloxacin-resistant enterobacteriaceae containing multiple gentamicin resistance-associated integrons in a Dutch hospital.

In a hematology unit in the Netherlands, the incidence of ciprofloxacin-resistant Enterobacter cloacae and Escherichia coli increased from from 1996 to 1999. Clonal spread of single genotypes of both ciprofloxacin-resistant E. coli and Enterobacter cloacae from patient to patient was documented by pulsed-field gel electrophoresis and random amplification of polymorphic DNA. In addition, genetically heterogeneous strains were isolated regularly. Integrons associated with gentamicin resistance were detected in Enterobacter cloacae and E. coli strains. Integron-containing E. coli were detected in all hematology wards. In contrast, in Enterobacter cloacae strains two integron types were encountered only in the isolates from one ward. Although in all patients identical antibiotic regimens were used for selective decontamination, we documented clear differences with respect to the nosocomial emergence of ciprofloxacin-resistant bacterial strains and gentamicin resistance-associated integrons.

Clinical features and risk factors of lactic acidosis following long-term antiretroviral therapy: 4 fatal cases.

Our objective was to describe clinical features and predisposing factors attributed to lactic acidosis in 4 HIV-infected patients on long-term nucleoside reverse transcriptase inhibitor (NRTI) therapy. All patients had received at least 6-20 months of NRTI-containing antiretroviral therapy: all used stavudine (d4T), in one combined with lamivudine (3TC), in the other 3 with didanosine (ddI); in one hydroxyurea was added. In all, the initial symptoms were gastrointestinal (nausea and vomiting), followed by tachypnoea preceding the lactic acidosis; death followed 6-22 days after admission (liver failure and uncontrollable arrhythmias). Treatment with riboflavin was unsuccessful in one patient. The only definite risk factor in all cases was NRTI-induced mitochondrial toxicity; one patient was concomitantly treated for Kaposi's sarcoma (with bleomycin and vinblastine) and one just recovered from pneumococcal sepsis. None of the patients had a history of chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. In all patients, some sort of toxicity to other previously used NRTIs had occurred earlier. Lactic acidosis occurred after months of NRTI therapy in patients who had already suffered other forms of NRTI toxicity. Concomitant diseases or comedication might have aggravated the mitochondrial toxicity of the NRTIs. Screening methods to detect mitochondrial toxicity are necessary, since lactic acidosis occurs rather unexpectedly, with a rapid, fatal course.

Quantitative galactomannan detection is superior to PCR in diagnosing and monitoring invasive pulmonary aspergillosis in an experimental rat model.

Two diagnostic tests, an Aspergillus-specific PCR and an enzyme-linked immunosorbent assay (ELISA) for the quantitative determination of galactomannan, were compared for diagnosing and monitoring invasive pulmonary aspergillosis. Persistently neutropenic rats with left-sided invasive pulmonary aspergillosis were sacrificed at regular intervals after inoculation. Blood samples and bronchoalveolar lavage (BAL) fluid were cultured and tested by PCR as well as by ELISA. Disseminated fungal infection in extrapulmonary organs was determined. The sensitivity of the ELISA was higher than that of the PCR on all days of measurements, in both blood and BAL fluid. Positive PCR or ELISA results in blood were not significantly associated with disseminated fungal infection. Serial testing in a separate group of rats showed consistently increasing concentrations of circulating galactomannan during the course of disease, while a positive PCR could be followed by negative results. The concentration of galactomannan was highly predictive for the time of survival (P < 0.0001). It was concluded that, in this model, quantitative galactomannan detection is superior to PCR in diagnosing and monitoring invasive pulmonary aspergillosis.

Aspergillus osteomyelitis after liver transplantation: conservative or surgical treatment?

We report on a liver transplant recipient who developed coxarthritis and lumbar spondylodiscitis due to Aspergillus flavus. He was treated with high-dose liposomal amphotericin B for 2 months followed by itraconazole. Because of intractable pain and severe, irreversible damage of the left hip, a Girdlestone resection was performed. The spondylodiscitis was treated successfully with anti-fungal agents only, which indicates that, in the absence of neurological impairment, good clinical outcome can be achieved without surgery. This case demonstrates that surgical therapy, which is often proclaimed as unavoidable for the treatment of Aspergillus osteomyelitis, should be considered in particular in the case of intolerable pain due to irreversible joint damage or involvement of vital organs.

New developments in the diagnosis and management of invasive fungal infections.

Invasive fungal infections in cancer patients are on the increase. Candidemia is now the fourth leading cause of bloodstream infections in many intensive care units (ICUs). Although a number of risk factors have been identified, antifungal therapy should not be started in non-neutropenic patients until a diagnosis of invasive candidiasis or candidemia is made or presumed in order to avoid the development of resistance. Even a single positive blood culture should be treated, and requires removal of intravascular lines. Fluconazole is the first line agent for treatment candidemia other than that caused by Candida glabrata or C. krusei. High-resolution CT scan pictures showing a halo sign or crescent air sign are helpful for establishing the diagnosis of invasive aspergillosis. Sandwich ELISA can be used to detect circulating galactomannan in serial serum samples. Polymerase chain reaction (PCR) of blood samples may also be used. There are only a few randomized studies of newly developed antifungal drugs compared to conventional amphotericin B (AmB). So far, both AmB colloidal dispersion and AmB lipid complex have failed to show more favorable efficacy or lesser toxicity rates, except for nephrotoxicity. Liposomal AmB, used during febrile neutropenia, did have a significantly lower toxicity rate. In neutropenic patients with invasive fungal infections liposomal AmB proved to be better than conventional AmB in terms of clinical efficacy, mortality and nephrotoxicity rates. The use of tests to achieve an earlier diagnosis combined with more potent treatment formulations such as liposomal AmB may be significant steps towards successful management of invasive fungal infections.

Hickman catheter-related infections in neutropenic patients: insertion in the operating theater versus insertion in the radiology suite.

PURPOSE: To determine the influence of microbial air quality during Hickman catheter insertion in the operating theater versus insertion in the radiology suite on the incidence of catheter-related infections (CRIs). PATIENTS AND METHODS: Hemato-oncologic patients with prolonged neutropenia on antimicrobial prophylaxis were entered onto the study. Catheters were inserted by experienced radiologists under sonographic and fluoroscopic guidance. RESULTS: Forty-eight Hickman catheters in 39 patients were inserted (23 in the operating theater, 25 in the radiology suite). CRIs were seen in 16 catheters (33%; six per 1,000 catheter days; eight in each group). Local infections were found in nine catheters (22%; six in the operating theater v three in the radiology suite; not significant [NS]), catheter-related bacteremia was found in 10 (29%; three in the operating theater v seven in the radiology suite; NS). Coagulase-negative staphylococci (CoNS) caused all CRIs. Despite early vancomycin therapy, 11 (69%; four in the operating room group v seven in the radiology suite group; NS) of the catheters with CRIs had to be removed prematurely. At 90 days after insertion, catheter survival was 78% and 60% (NS) for the operating room and radiology suite, respectively. Multivariate analysis showed that neutropenia increased the CRI risk 20-fold (P =.004) and was strongly related to premature catheter removal owing to infection (relative risk = 11.9; P =.009). Neutropenia on the day of insertion was also significantly correlated with CRI (P =.04) and premature catheter removal owing to infection (P =.03). Serial cultures of blood, exit site, and catheter hub did not predict the development of CRI. CONCLUSION: The high incidence of Hickman CRI caused by CoNS was not associated with insertion location (operating theater v radiology suite). Neutropenia, including neutropenia on the day of insertion, was a significant risk factor for CRI and infection-related catheter removal.

Urological complaints in relation to indinavir plasma concentrations in HIV-infected patients.

OBJECTIVE: To assess the relationship between indinavir-associated urological complaints and indinavir plasma concentrations. DESIGN: Case series, comparing indinavir plasma concentrations in cases with average concentrations in a control group. METHODS: Patients taking 800 mg indinavir three times a day (tid), who presented with overt urological complaints (renal colic, flank pain or haematuria) were selected for the study. Plasma indinavir concentrations were measured by means of a standardized high performance liquid chromatography (HPLC) method. Plasma samples taken at 1.5-8 h after the last indinavir ingestion were included for evaluation. Results were compared with the full pharmacokinetic curves of indinavir plasma concentrations from a control group of 14 patients taking 800 mg indinavir tid without urological complaints, and were expressed as concentration ratios. A ratio of 1 indicated a plasma concentration equalling the average concentration in the control population at the same point in time after the ingestion of indinavir. RESULTS: Seventeen patients (five women) were enrolled and the indinavir concentrations of 15 patients could be evaluated. Fourteen (93%) patients had a concentration above the mean of the controls, 12 (80%) patients had a concentration above the upper 95% confidence limit, and one (7%) patient had a concentration below the lower 95% confidence limit. The mean indinavir concentration in patients with urological complaints (ratio range 0.55-11.49) was significantly higher than the average concentration and the upper 95% confidence limit of the control group (P < 0.05). The results could not be explained by differences in weight, sex or drug interactions. Two patients had chronic active hepatitis B infection. In six patients with indinavir concentrations above the upper 95% limit, indinavir was reduced to 600 mg tid. Upon repeat measurement after the dose adjustment, their indinavir plasma concentrations fell within the 95% confidence interval around the mean of the control population. All six patients remained asymptomatic and had viral loads of less than 500 copies per ml after a follow-up of 5-16 months. CONCLUSIONS: Urological complications occurring during indinavir treatment were associated with elevated indinavir plasma concentrations in 80% of patients in this study. Indinavir plasma concentrations should be monitored upon presentation of urological complaints, on the basis of which dose reductions may be applied if brief interruption and increased hydration are ineffective.

Scintigraphic imaging of bacterial and fungal infection in granulocytopenic rats.

UNLABELLED: Scintigraphic imaging in granulocytopenic patients can be very useful to detect and localize infections, which often do not show localizing signs and symptoms. We studied the potential of 99mTc-labeled polyethylene glycol (PEG)-coated liposomes and 99mTc-labeled IgG to image bacterial and fungal infection in a granulocytopenic rat model. 67Ga-citrate was used as a reference agent. METHODS: 99mTc-PEG-liposomes, 99mTc-hydrazinonicotinate (HYNIC)-IgG or 67Ga-citrate was administered to granulocytopenic rats with a Staphylococcus aureus abscess or with unilateral invasive pulmonary aspergillosis. Imaging and biodistribution studies were performed. RESULTS: All agents visualized the S. aureus infection from 1 h after injection onward. However, only with 99mTc-PEG-liposomes and with 99mTc-HYNIC-IgG did activity in the infectious foci increase with time up to 24 h. 99mTc-PEG-liposomes and 99mTc-HYNIC-IgG showed significantly higher accumulation in the infectious focus compared with 67Ga-citrate (1.33+/-0.31 and 1.40+/-0.16 percentage injected dose per gram [%ID/g], respectively, versus 0.31+/-0.04 %ID/g 24 h after injection; P<0.05). At 24 h after injection, abscess-to-muscle ratios were highest for 99mTc-liposomes (72.1+/-19.1), followed by 99mTc-HYNIC-IgG (18.3+/-3.3) and 67Ga-citrate (4.4+/-0.7). In pulmonary aspergillosis, both 99mTc-PEG-liposomes and 99mTC-HYNIC-IgG showed significantly higher uptake in the infected lung than did 67Ga-citrate (3.6+/-0.4 and 8.3+/-0.8 %ID/g, respectively, versus 1.3 %ID/g at 24 h after injection; P<0.05). CONCLUSION: 99mTc-PEG-liposomes and 99mTc-HYNIC-IgG performed better than did 67Ga-citrate in the localization of peripheral bacterial infection and fungal infection in the lung in granulocytopenic rats. The high focal uptake and high target-to-nontarget ratios of 99mTc-PEG-liposomes and 99mTc-HYNIC-IgG indicate that both radiopharmaceuticals may become valuable agents to image infection in granulocytopenic patients.

Liposomal amphotericin B compared with amphotericin B deoxycholate in the treatment of documented and suspected neutropenia-associated invasive fungal infections.

It has been suggested that a better outcome of neutropenia-associated invasive fungal infections can be achieved when high doses of lipid formulations of amphotericin B are used. We now report a randomized multicentre study comparing liposomal amphotericin B (AmBisome, 5 mg/kg/d) to amphotericin B deoxycholate (AmB, 1 mg/kg/d) in the treatment of these infections. Of 106 possible patients, 66 were enrolled and analysed for efficacy: nine had documented fungaemia, 17 had other invasive mould infections and 40 had suspected pulmonary aspergillosis. After completion of the course medication, in the AmBisome group (n = 32) 14 patients had achieved complete response, seven a partial response and 11 were failures as compared to 6, 13 and 15 patients (n = 34) treated with AmB (P=0.09); P=0.03 for complete responders. A favourable trend for AmBisome was found at day 14, in patients with documented infections and in patients with pulmonary aspergillosis (P=0.05 and P=0.096 respectively). Mortality rates were lower in patients treated with AmBisome (adjusted for malignancy status, P=0.03). More patients on AmB had a >100% increase of their baseline serum creatinine (P<0.001). The results indicate that, in neutropenic patients with documented or suspected invasive fungal infections AmBisome 5 mg/kg/d was superior to AmB 1 mg/kg/d with respect to efficacy and safety.

Clonal expansion of Staphylococcus epidermidis strains causing Hickman catheter-related infections in a hemato-oncologic department.

The detailed analysis of 411 strains of coagulase-negative staphylococci (CoNS) obtained from 40 neutropenic hemato-oncologic patients (61 Hickman catheter episodes) on intensive chemotherapy is described. By random amplification of polymorphic DNA (RAPD) analysis, a total of 88 different genotypes were detected: 51 in air samples and 30 in skin cultures prior to insertion, 12 in blood cultures after insertion, and only 5 involved in catheter-related infections (CRI). Two RAPD genotypes of Staphylococcus epidermidis predominated, and their prevalence increased during patient hospitalization. At insertion, these clones constituted 11 of 86 (13%) CoNS isolated from air samples and 33 of 75 (44%) CoNS isolated from skin cultures. After insertion, their combined prevalence increased to 33 of 62 (53%) in catheters not associated with CRI and 139 of 188 (74%) in catheters associated with CRI (P = 0.0041). These two predominant S. epidermidis clones gave rise to a very high incidence of CRI (6.0 per 1,000 catheter days) and a very high catheter removal rate for CRI, 70%, despite prompt treatment with vancomycin. A likely source of S. epidermidis strains involved in CRI appeared to be the skin flora in 75% of cases. The validity of these observations was confirmed by pulsed-field gel electrophoresis (PFGE) of SmaI DNA macrorestriction fragments of blood culture CoNS isolates. Again, two predominant CoNS genotypes were found (combined prevalence, 60%). RAPD and PFGE yielded concordant results in 75% of cases. Retrospectively, the same two predominant CoNS clones were also found among blood culture CoNS isolates from the same hematology department in the period 1991 to 1993 (combined prevalence, 42%) but not in the period 1978 to 1982. These observations underscore the pathogenic potential of clonal CoNS types that have successfully and persistently colonized patients in this hemato-oncology department.

Bioavailability of ciprofloxacin after multiple enteral and intravenous doses in ICU patients with severe gram-negative intra-abdominal infections.

BACKGROUND: Few data are available on the pharmacokinetics of multiple enteral dosing of ciprofloxacin in critically ill intensive care patients and none for those with severe gram-negative intra-abdominal infections (GNIAI). OBJECTIVE: To determine the bioavailability of enteral ciprofloxacin in tube-fed intensive care patients with severe GNIAI. DESIGN: A randomized crossover study. SETTING: University-based medical center. PATIENTS: 5 critically ill intensive care patients with GNIAI and an estimated creatinine clearance > 25 ml/ min who received continuous tube feeding. INTERVENTIONS: Multiple doses of enteral 750 mg b.i.d. versus 400 mg b.i.d.i.v. ciprofloxacin. MEASUREMENTS: The calculated 12-h area under the serum concentration versus time curve after 750 mg b.i.d. enteral dosing was equivalent to that after 400 mg b.i.d.i.v. The mean bioavailability of enteral dosing was 53.1% [95% confidence interval (CI) 43.5-62.8]. In seven additional patients, the mean serum steady-state concentration at 2 h after enteral administration was 3.9 microg/ml (95% CI 1.9-5.9), not significantly different from that found in the crossover study (p = 0.4). CONCLUSIONS: In tube-fed intensive care patients with severe GNIAI, the bioavailability of enteral ciprofloxacin is adequate.

Infectious complications of radiologically inserted Hickman catheters in patients with hematologic disorders.

PURPOSE: To assess the incidence of infections and its influence on the survival of radiologically inserted Hickman catheters (HCs) in patients with hematologic disorders and to determine factors associated with premature HC removal. METHODS: Survival and complications of 175 HCs in 115 patients were studied retrospectively. To describe the data the Kaplan-Meier method and the log-rank test were used, using the date of HC removal due to HC-related infection as endpoint. A stratified Cox regression model was used to determine explanatory factors. RESULTS: Seventy (40%) HCs were removed prematurely because of proven or probable HC-related infections. The incidence of infection leading to HC removal was 4. 78 per 1000 catheter-days for proven HC infections. Univariate analysis revealed that acute myeloid leukemia, acute lymphocytic leukemia, or treatment for these diseases, gender, each subsequent catheter in the same patient and insertion site increased the risk of premature removal of the catheter due to infection. CONCLUSION: Infection is a major problem in patients with HCs. Unfortunately, the factors associated with increased infection rates that were found in this study cannot be influenced. Further studies are necessary to determine the role of environmental conditions in a radiology suite in relation to the risk of developing a catheter-related infection.

New approaches to antifungal chemotherapy.

The antifungal agents currently available to treat invasive fungal infections are limited in both number and usefulness. Treatment with the polyene amphotericin B (AmB), and with several azoles, in particular fluconazole and itraconazole, is the mainstay of antifungal chemotherapy. However, the clinical usefulness of these drugs is hampered by drawbacks associated with their safety and/or efficacy. There are two approaches to overcome this situation. One is to discover and develop new antifungal agents or formulations with advantages over and/or complementary to existing drugs. For this purpose, the following three categories of new drugs have been the major targets of study and development: (i) lipid formulations of polyenes, (ii) azoles (including cyclodextrin-complexes), and (iii) nonazole compounds, particularly those of microbial origin (antibiotics).

Risk factors for meningitis after transsphenoidal surgery.

To evaluate possible risk factors for meningitis, we retrospectively reviewed 228 transsphenoidal operations (in which a standard regimen of amoxicillin prophylaxis was used) for sellar pathology. The incidence of meningitis was 3.1% (seven of 228 cases). Cultures of preoperative specimens from the anterior nasal vestibule in three of seven patients yielded Staphylococcus aureus, but none of these patients developed S. aureus meningitis. Two of three patients with significant preoperative paranasal sinus abnormalities developed meningitis compared with only five of 225 patients without significant paranasal sinus abnormalities (P < .005). Three of 22 patients with intraoperative cerebrospinal fluid (CSF) leakage developed meningitis compared with four of 206 patients without intraoperative CSF leakage (P < .05). Six of seven patients with postoperative CSF rhinorrhea and only one of 221 patients without postoperative CSF rhinorrhea developed meningitis (P < .00001). In conclusion, postoperative CSF leakage is an important risk factor for meningitis after transsphenoidal surgery. Cultures of preoperative specimens from the anterior nasal vestibule did not have any predictive value in our study.

Liposomal amphotericin B (AmBisome) compared with amphotericin B both followed by oral fluconazole in the treatment of AIDS-associated cryptococcal meningitis.

OBJECTIVE: Amphotericin B deoxycholate initial therapy and fluconazole maintenance therapy is the treatment of choice for AIDS-associated cryptococcal meningitis. However, the administration of amphotericin B is associated with considerable toxicity. A potential strategy for reducing the toxicity and increasing the therapeutic index of amphotericin B is the use of lipid formulations of this drug. DESIGN AND METHODS: HIV-infected patients with cryptococcal meningitis were randomized to treatment with either liposomal amphotericin B (AmBisome) 4 mg/kg daily or standard amphotericin B 0.7 mg/kg daily for 3 weeks, each followed by fluconazole 400 mg daily for 7 weeks. During the first 3 weeks, clinical efficacy was assessed daily. Mycological response was primarily evaluated by cerebrospinal fluid (CSF) cultures at days 7, 14, 21 and 70. RESULTS: Of the 28 evaluable patients, 15 were assigned to receive AmBisome and 13 to receive amphotericin B. Baseline characteristics were comparable. The time to and the rate of clinical response were the same in both arms. AmBisome therapy resulted in a CSF culture conversion within 7 days in six out of 15 patients versus one out of 12 amphotericin B-treated patients (P = 0.09), within 14 days in 10 out of 15 AmBisome patients versus one out of nine amphotericin B patients (P = 0.01), and within 21 days in 11 out of 15 AmBisome patients versus three out of eight amphotericin B patients (P = 0.19). When Kaplan-Meier estimates were used to compare time to CSF culture conversion, AmBisome was more effective (P < 0.05; median time between 7 and 14 days for AmBisome versus > 21 days for amphotericin B). AmBisome was significantly less nephrotoxic. CONCLUSIONS: A 3-week course of 4 mg/kg AmBisome resulted in a significantly earlier CSF culture conversion than 0.7 mg/kg amphotericin B, had equal clinical efficacy and was significantly less nephrotoxic when used for the treatment of primary episodes of AIDS-associated cryptococcal meningitis.