Mg Of Amphotericin Research Articles

Optimal lameness induction model development using amphotericin B in meat goats.

Lameness continues to be a critical health and welfare concern associated with goat production. Amphotericin B (amp B) is an antimicrobial successful in inducing transient lameness for research purposes previously in livestock animals. The objectives of this study were to (1) identify which of three varying doses of amp B would be most effective in inducing lameness in meat type goats and (2) develop a facial grimace scale for goats. Lameness was produced by an intra-articular injection of amphotericin B into the left hind lateral claw distal interphalangeal joint with either a 5 mg/0.25 mL (high-low, 5 mg of amphotericin B in a volume of 0.25 mL), 5 mg/0.5 mL (high-high, 5 mg of amphotericin B in a volume of 0.5 mL), or a 2.5 mg/0.25 mL (low-low, 2.5 mg of amphotericin B in a volume of 0.25 mL). A saline treatment of 0.5 mL was used as control (0.9% sterile saline solution). Lameness response was analyzed by infrared thermography (IRT) at the induced joint, mechanical-nociception threshold (MNT), visual lameness scoring (VLS), a visual analogue scale (VAS), kinetic gait analysis (KGA), plasma cortisol (CORT), substance P (Sub P), and behavior scoring. The IRT and MNT values differed by timepoint (P ≤ 0.0001). Results from VLS showed the HL treatment was the most effective at inducing lameness (6/6 goats became lame compared to HH 4/6 and LL 2/6). At 24, 48, and 72 h, VAS scores were significantly higher when comparing HL to all other treatment groups (P = 0.0003). Both behavior observers (1 and 2) reported a significant time effect (P = 0.05), with goats exhibiting more facial grimacing at 24 h post-lameness induction. From these data, an optimal dose for a repeatable lameness induction model in goats was aquired. An effective Goat Grimace Scale (GGS) was also developed to evaluate pain responses in goats.

P303 An unusual case of isolated gluteal abscess

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMBackgroundMucormycosis is an invasive infection caused by fungi belonging to the order Mucorales. The angioinvasive disease caused by these fungi can prove to be fatal despite appropriate treatment. We report an unusual case of a gluteal abscess caused by a probable mucormycosis in an apparently immunocompetent individual.Case DescriptionA 68-year-old gentleman hailing from a rural area of Bihar, India presented with a painful swelling over the left buttock region for 4 weeks. He was a known hypertensive and had ischemic heart disease. He denied any history of fever. The lump had gradually increased in size. He was a retired school teacher with a farmland and reared livestock at home. He was a non-vegetarian and denied any addictions. He had a history of intermittent lower backache for which he used to take occasional intramuscular analgesic injections over his buttocks from a local medical practitioner.On examination, the swelling was about 4 cm X 4 cm in size, fluctuant, with ill-defined margins over the lateral region of the left buttock. The swelling was tender, warm, and not fixed to underlying structures. Systemic examination was unremarkable. Ultrasound examination revealed an ∼7.2 × 4.2 × 7.8 cm cystic lesion with a volume of 126cC. It was located predominantly in subcutaneous fat extending into muscular plane with septa and solid components in the left gluteal region (Fig. 1). It had thick walls and fine internal echoes within. Other investigations were unremarkable except for glycosylated Hb, which was 6.2%. Incision and drainage were done.During the procedure, it was seen as a cyst with a thick wall that was removed in toto. The contents were explored after removal and were found to be yellowish black with mucoid consistency. Histopathological examination revealed numerous broad, ribbon-like, aseptate fungal hyphae with right-angled branching infiltrating the inflamed tissue (Fig.2). There were numerous epithelioid granulomas surrounding the fungal elements in the soft tissue of the wall. The findings were consistent with a fungal abscess caused by mucormycosis. Culture of the fluid/pus was negative. Thus, a diagnosis of mucormycotic gluteal abscess was made and patient was commenced on 50 mg of amphotericin B deoxycholate in view of financial restraints. High resolution computed tomography of chest was done which was unremarkable.He developed an acute kidney injury after 2 doses of amphotericin B deoxycholate which was then stopped. Oral posaconazole was started. He has developed bilateral leg swelling post-oral posaconazole and is commenced on oral spironolactone for the same. The postoperative wound has healed well and there is no new swelling or tenderness over the area. He is planned for further follow-up.ConclusionsIsolated gluteal abscess caused by mucormycosis is rare in an apparently immunocompetent host.We assume that repeated intramuscular injections might have caused traumatic inoculation of fungus into the host which led to this outcome.

Randomized controlled trial comparison of analgesic drugs for control of pain associated with induced lameness in lactating dairy cattle

Both the economic loss and welfare implications of lameness affect the dairy industry. Currently no analgesic drugs are approved to alleviate lameness-associated pain in lactating dairy cattle in the United States. In this randomized controlled trial, 48 lactating Holsteins were enrolled to evaluate the effect of oral meloxicam and i.v. flunixin meglumine on induced lameness. Cows were allocated to 1 of 4 treatment groups (n = 12 per group): lameness and flunixin meglumine (LAME + FLU); lameness and meloxicam (LAME + MEL); lameness and placebo (LAME + PLBO); or sham induction and placebo (SHAM + PLBO). Six hours before treatment, arthritis-synovitis was induced in the distal interphalangeal joint with 20 mg of amphotericin B, whereas SHAM cows were given an intra-articular injection of an equal volume (4 mL) of isotonic saline. Cows in LAME + FLU received 2.2 mg/kg flunixin meglumine i.v. and whey protein placebo orally; LAME + MEL were administered 1 mg/kg meloxicam orally and 2 mL/45 kg sterile saline placebo i.v.; LAME + PLBO were administered 2 mL/45 kg sterile saline placebo i.v. and whey protein placebo orally; and SHAM + PLBO received 2 mL/45 kg sterile saline placebo i.v. and whey protein placebo orally. The initial treatment of MEL, FLU, or PLBO was identified as time 0 h and followed by a second dose 24 h later with data collection for 120 h. The methods used to assess analgesic efficacy were electronic pressure mat, visual lameness assessment, visual analog score, plasma cortisol concentration, plasma substance P concentration, mechanical nociception threshold, and infrared thermography imaging. Linear mixed effect modeling was the primary method of statistical analysis. Visual lameness scoring indicated a lower proportion of the FLU + LAME group was lame at the T2 h and T8 h time points in comparison to the positive controls, whereas MEL therapy resulted in a lower proportion of lame cows at the T8 h time point. Cortisol area under the effect curve was lower following FLU therapy compared with LAME + PBLO for the 0-2 h (LSM difference = 35.1 ng·h/mL, 95% CI: 6.8, 63.3 ng·h/mL), 2-8 h (LSM difference = 120.6 ng·h/mL, 95% CI: 77.2, 164.0 ng·h/mL), and 0-24 h (LSM difference = 226.0 ng·h/mL, 95% CI: 103.3, 348.8 ng·h/mL) time intervals. Following MEL therapy, cortisol area under the effect curve was lower than LAME + PLBO for both the 2 to 8 h (LSM difference = 93.6 ng·h/mL, 95% CI: 50.2, 137.0 ng·h/mL) and 0 to 24 h time intervals (LSM difference = 187.6 ng·h/mL, 95% CI: 64.9, 310.4 ng·h/mL). Analysis of data from other assessment modalities failed to discern biologically relevant differences between treatment groups. We conclude that meaningful differences were evident for visual lameness assessment and cortisol from MEL and FLU treatment versus the positive control. Further clinical research is needed toward development of a model that will create reproducible events that are more pronounced in severity and duration of lameness which can be validated as a substitute for naturally occurring lameness cases.

Identification of Two Pathogens in a Culture‐Negative Prosthetic Joint Infection Using Nanopore Sequencing

Periprosthetic joint infection (PJI) following total joint arthroplasty (TJA) is challenging to diagnose due to lower yield in pathogenic identification (~50%) using conventional microbiologic culture techniques. Here we present a case in which two pathogens were detected using nanopore sequencing from a 50 year‐old male with a suspected, yet culture‐negative, PJI. Three swabs were taken from multiple sites of drainage surrounding the suspected infected right knee joint following a routine arthroplasty (original TKA was done three years prior). DNA was extracted from the swabs using the MasterPure™ Gram Positive DNA Purification Kit (Lucigen). Sample libraries were prepared using the Rapid PCR Barcoding Kit (Oxford Nanopore Technologies) and sequenced on a v9.4.1 MinION flow cell. A total of 1,056,710 reads from all three swabs combined were aligned using a minimum Q score of 7.0 to the RefSeq database on the EPI2ME platform using the “What’s in my pot?” app. A total of 5,540 reads (0.52%) aligned to the bacteria Corynebacterium with the most abundant species being detected as Corynebacterium simulans. A total of 1,886 (0.18%) mapped to the fungi Malassezia globosa. Due to the patient having a visible arthrocutaneous fistula combined with visualized drainage from the joint using a methylene blue challenge test, the prosthetic knee was removed and an antibiotic spacer that contained 6 gm vancomycin, 7.2 gm tobramycin and 100 mg of amphotericin B was implanted. The patient also received a 6 week course of ceftriaxone infusions and has shown rapid clinical improvement. While our sequencing results were not used directly for patient care in this case, it demonstrates the promise that nanopore sequencing has for future use in infectious disease diagnostics.

Effects of transdermal flunixin meglumine on experimentally induced lameness in adult dairy cattle

Lameness is a common animal health condition with significant production and welfare implications. The transdermal formulation of flunixin meglumine is the only approved drug for pain control in cattle in the United States. Thirty adult dairy cows were enrolled in a study to determine the effect of transdermal flunixin on cattle with induced lameness. Cows were allocated to 1 of 3 treatment groups, with 10 cows per group: lameness and flunixin (L+F), lameness and placebo (L+P), or sham induction and placebo (S+P). An arthritis-synovitis was induced in the distal interphalangeal joint of the left hind lateral digit, using 20 mg of amphotericin B, 6 h before the application of treatment. Cows enrolled into the sham induction group had 4 mL of isotonic saline injected into the joint. Cows were dosed with transdermal flunixin at 3.33 mg/kg (1 mL/15 kg), or a placebo at 1 mL/15 kg, every 24 h for 3 d. The first treatment of flunixin or placebo was considered the start of the study, identified as time 0 h. Data were collected from all cows for 120 h following the initial treatment application. Outcome measures included plasma cortisol; substance P; visual lameness assessment; mechanical nociception threshold (MNT), presented as difference between left and right feet; infrared thermography (IRT), presented as difference between left and right feet; and gait analysis using a pressure mat. Cortisol concentrations were lower for the L+F group starting at 1.5 h after drug administration. Substance P levels showed no evidence for treatment differences among groups. Differences between the left hind MNT and right hind MNT were detected, with S+P having the lowest difference at -0.04 kilograms-force (kgf; 95% CI: -1.86 to 1.78 kgf), and L+P having the highest at -2.96 kgf (95% CI: 1.55 to 4.36 kgf). The L+F group was intermediate at -2.08 kgf (95% CI: 0.89 to 3.27 kgf). Similarly, when the difference between the maximum temperatures of the coronary band were examined via IRT, the L+P group had the highest difference at 1.64°C (95% CI: 1.02 to 2.26°C), with the L+F and S+P groups measuring 0.57°C (95% CI: 0.06 to 1.08°C) and 0.53°C (95% CI: -0.2 to 1.25°C) respectively. We found no evidence for differences among treatment groups when analyzing force, contact pressure, step impulse, or stride length. Based on differences in MNT, IRT, and cortisol, transdermal flunixin is an effective analgesic agent for induced lameness. Multiple doses of transdermal flunixin may be required to be clinically effective, based on MNT and IRT data. Further investigation of transdermal flunixin and its analgesic effects is warranted in naturally occurring lameness.

1138. Retrospective Cohort Analysis of Amphotericin B Nephrotoxicity in Kidney Transplant Recipients

BackgroundTreatment of invasive fungal infections with amphotericin B is a concern in kidney transplant patients due to fear of allograft loss. Reluctance to use amphotericin B may lead to suboptimal therapy and poor treatment outcomes. The risk of amphotericin B-related nephrotoxicity and allograft dysfunction has not been studied in kidney transplant patients. Our aim was to study the association between amphotericin B and acute kidney injury (AKI) as defined by the Acute Kidney Injury Network classification, allograft loss and patient mortality in kidney transplant recipients.MethodsWe used SPSS to conduct a descriptive analysis of a retrospective cohort of 30 adult kidney transplant recipients who were admitted to Virginia Commonwealth University Medical Center and received treatment with amphotericin B from 2005 to 2015.ResultsThe median age in our cohort was 57. 40% were female, 60% were male. 60% had received a kidney transplant from a deceased donor; 13.3% from a living related donor; 13.3% from a living unrelated donor; and 13.3% had received a combined kidney–pancreas transplant. 63.3% of patients had received liposomal amphotericin B; 33.3% had received lipid-complex amphotericin B; 3.3% had received conventional amphotericin B. We found an association between cumulative amphotericin B doses above 5,000 mg and AKI, whereby 64.7% of patients exposed to less than 5,000 mg of amphotericin B developed AKI and 100% of patients exposed to more than 5,000 mg of amphotericin B developed AKI (P = 0.017). We did not find an association between cumulative amphotericin B doses above 5,000 mg and return to dialysis at 3 months and 12 months post-exposure (P = 0.436 and 0.288, respectively). We also did not find an association between such doses of amphotericin B and mortality at 30 and 90 days (P = 0.869 and 0.193, respectively).ConclusionIn the first descriptive analysis of a retrospective cohort of kidney transplant patients exposed to amphotericin B, our results suggest that the risk of nephrotoxicity may be significantly increased when a cumulative dose of 5,000 milligrams is exceeded. Our results also suggest that amphotericin B doses associated with nephrotoxicity in kidney transplant patients may not have an effect on allograft survival and patient mortality.Disclosures All authors: No reported disclosures.

Survival of a patient with pulmonary Cunninghamella bertholletiae infection without surgical intervention

Mucormycosis is an uncommon fungal infection, which generally develops in immunosuppressed hosts. In particular, pulmonary infection by Cunninghamella bertholletiae, a rare species of Mucor, is characterized by invasiveness and high mortality. Herein a case of pulmonary mucormycosis due to C. bertholletiae in a female patient with chronic renal insufficiency, secondary to microscopic polyarteritis, is reported. The patient survived after successful treatment with a cumulative dose of 1508 mg of amphotericin B, phased reduction of glucocorticoid therapy and chest tube drainage of a pneumothorax, without the necessity for surgical intervention. This case demonstrates that conservative therapy may be effective in patients for whom surgical intervention is not an option.

Compartmentalized Intrapulmonary Pharmacokinetics of Amphotericin B and Its Lipid Formulations

We investigated the compartmentalized intrapulmonary pharmacokinetics of amphotericin B and its lipid formulations in healthy rabbits. Cohorts of three to seven noninfected, catheterized rabbits received 1 mg of amphotericin B deoxycholate (DAMB) per kg of body weight or 5 mg of either amphotericin B colloidal dispersion (ABCD), amphotericin B lipid complex (ABLC), or liposomal amphotericin B (LAMB) per kg once daily for a total of 8 days. Following sparse serial plasma sampling, rabbits were sacrificed 24 h after the last dose, and epithelial lining fluid (ELF), pulmonary alveolar macrophages (PAM), and lung tissue were obtained. Pharmacokinetic parameters in plasma were derived by model-independent techniques, and concentrations in ELF and PAM were calculated based on the urea dilution method and macrophage cell volume, respectively. Mean amphotericin B concentrations +/- standard deviations (SD) in lung tissue and PAM were highest in ABLC-treated animals, exceeding concurrent plasma levels by 70- and 375-fold, respectively (in lung tissue, 16.24 +/- 1.62 versus 2.71 +/- 1.22, 6.29 +/- 1.17, and 6.32 +/- 0.57 microg/g for DAMB-, ABCD-, and LAMB-treated animals, respectively [P = 0.0029]; in PAM, 89.1 +/- 37.0 versus 8.92 +/- 2.89, 5.43 +/- 1.75, and 7.52 +/- 2.50 mug/ml for DAMB-, ABCD-, and LAMB-treated animals, respectively [P = 0.0246]). By comparison, drug concentrations in ELF were much lower than those achieved in lung tissue and PAM. Among the different cohorts, the highest ELF concentrations were found in LAMB-treated animals (2.28 +/- 1.43 versus 0.44 +/- 0.13, 0.68 +/- 0.27, and 0.90 +/- 0.28 microg/ml in DAMB-, ABCD-, and ABLC-treated animals, respectively [P = 0.0070]). In conclusion, amphotericin B and its lipid formulations displayed strikingly different patterns of disposition in lungs 24 h after dosing. Whereas the disposition of ABCD was overall not fundamentally different from that of DAMB, ABLC showed prominent accumulation in lung tissue and PAM, while LAMB achieved the highest concentrations in ELF.

Changes in MMP‐2 and ‐9 Activity and MMP‐8 Reactivity After Amphotericin B Induced Synovitis and Treatment with Bufexamac

The objective here was to evaluate the acute effects of induced arthritis on synovial fluid (SF) levels of matrix metalloproteinases (MMP) -2, -8 and -9 in horses. To evaluate MMP-2 and -9 activities and the effect of non-steroidal anti-inflammatory drug (NSAID) bufexamac during remission from acute arthritis. Aseptic arthritis was induced in 24 Standardbred horses using 20 mg of amphotericin B as a single intra-articular (IA) injection in the right intercarpal joint. After 1 week and 2 weeks, horses were treated intra-articularly with 10, 20, or 40 mg of bufexamac suspension or with sterile saline solution as control. SF was sampled prior to induction and at weekly intervals for 5 weeks. Fluids were evaluated for MMP-2 and MMP-9 activity by gelatin zymography or for MMP-8 immunoreactivity by Western Blotting. IA injection of amphotericin B consistently resulted in significant increase in the immunoreactivity of MMP-8 and activity of both the latent and the active forms of MMP-2 and -9, among which the active form of MMP-2 increased the most. MMP-9 levels declined to pre-induction levels within 2 weeks, whereas levels of MMP-2 remained still high after 5 weeks. Treatment with bufexamac did not significantly affect levels of gelatinolytic MMP. Results suggest that after acute arthritis of horses, elevated MMP activity is present in the joint, for several weeks, to a degree that could promote cartilage degradation, and treatment with the NSAID bufexamac is not likely to affect that. Furthermore, analysing levels of MMP-9 activity and especially levels of active forms of MMP-2 activity may be valuable to predict the time of occurrence of arthritis in horses.

Anti-infectious effect of sustained antravitreal amphotericin B drug delivery system on experimental rabbit fungal endophthalmitis of Candida albicans

To evaluate the efficacy and toxicity of sustained intravitreal amphotericin B drug delivery system (DDS) on experimental rabbit fungal endophthalmitis of Candida albicans. Fifty New Zealand rabbits received central vitrectomy were followed by Candida albicans suspension (10(4) colony forming unit, cfu) injection. Rabbits were grouped randomly into five with ten in each as follows: Group A, endophthalmitis control group; Group B, DDS of vehicle alone; Group C, topical treatment with amphotericin B eyedrop; Group D, 5 microg of amphotericin B intravitreal injection every week for two weeks; Group E, DDS contained 1 mg of amphotericin B. Slit-lamp and indirect-ophthalmoscope were performed at different time for two months and vitreous opacity was compared between each group. The intraocular drug concentration was measured with high performance liquid chromatography (HPLC). Light and electron microscope were conducted to evaluate the toxicity of DDS and the effect of vehicle on intraocular structure. Electroretinography (ERG) was employed to evaluate the function of retina before and after the implantation of DDS. Endophthalmitis was obviously inhibited in group E while vitreous was still opacity in other groups. The drug concentration in vitreous cavity was stable and remained for two months in group E while rapidly went down two weeks later in group D. No toxic evidence was found in ocular, liver and kidney tissue and retinal ultrastructure was normal. There was no difference in ERG study before and after the DDS was implanted. Sustained intravitreal amphotericin B DDS can significantly suppress the formation of fungal colony and inhibit the development of infection with long and stable intraocular drug concentration maintenance. The vehicle and amphotericin B DDS are safe to intraocular structure.

Intradialytic Administration of Amphotericin B: Clinical Observations on Efficacy and Safety

Amphotericin B is used commonly to treat fungal infections. Unfortunately, little information exists regarding the use of intravenous amphotericin B in patients with end-stage renal disease (ESRD). We retrospectively reviewed the clinical course of patients receiving amphotericin B during hemodialysis (HD). Twenty-five episodes of systemic fungal infection occurring in 24 patients with ESRD treated with parenteral amphotericin B administered during HD were noted. Patients received a maintenance dose of 0.5 to 1.0 mg/kg amphotericin B intravenously thrice weekly during HD sessions. Twenty-three patients received either 500 or 1000 mg of amphotericin B, whereas 1 patient with AIDS received a total of 6,500 mg. Intradialytic hypotension developed in 27.7% of HD sessions during treatment with amphotericin B compared with 28.8% of 20 HD sessions evaluated before initiation of amphotericin B therapy. Four patients exhibited a temperature rise greater than 38.8 degrees C during drug infusion (1 episode per patient). Increases in heart rate and ventricular ectopy were rare. Serum potassium concentrations as well as Kt/V and urea reduction ratio did not change significantly. All patients (except the patient with AIDS) resolved their respective fungal infections. Intradialytic administration of amphotericin B was generally well tolerated. Our observations suggest that amphotericin B is effective and safe for outpatient intradialytic therapy when administered according to protocol.

Activity of amphotericin B in lipid emulsion in the initial treatment of canine leishmaniasis.

Amphotericin B was given to 19 dogs with leishmaniasis. The drug was diluted in an emulsion prepared by mixing 50 mg of amphotericin B desoxycholate with 40 ml of sterile water and 10 ml of soya bean oil solution. The dogs were infused over nearly one hour with 50 ml/kg of normal saline followed by 10 ml/kg of mannitol 20 per cent. The mixture was then loaded over 30 to 60 minutes using a syringe pump. The emulsion was given twice weekly, at an increasing dosage (from 1 to 2.5 mg/kg bodyweight), for a minimum of eight injections. All 17 dogs receiving a total dosage of more than 10 mg/kg were clinically cured by the end of the treatment, and 14 of these had a negative polymerase chain reaction test on bone marrow.

Efficacy of recombinant gamma interferon for treatment of systemic cryptococcosis in SCID mice.

We have previously shown that gamma interferon (IFN-gamma) is a useful adjunct to therapy of experimental systemic cryptococcosis in normal mice. To better emulate AIDS patients, SCID mice were infected intravenously with Cryptococcus neoformans. Mice received no therapy, 3 mg of amphotericin B (AmB) per kg of body weight, or 10(5) U of IFN-gamma alone (prophylactically and therapeutically or only therapeutically) or with AmB. In the first experiment, >75% of the mice survived. Therapy with AmB alone was efficacious compared to no therapy in all organs. Both regimens of IFN-gamma alone were efficacious in the brain and lungs, and the combination of AmB and IFN-gamma showed significant synergy in the kidneys. AmB alone cured 40% of mice of infection, whereas the combination regimens cured >50% of the mice and 90% of the brain infections. In a second study, IFN-gamma again proved efficacious alone, and when given with AmB its efficacy was improved. Therapeutic IFN-gamma alone was effective only in the liver compared to no therapy, and the combination regimen, although highly effective, showed no significant synergy. In a third experiment, AmB alone or in combination with IFN-gamma prolonged survival compared to no therapy or IFN-gamma alone. The combination regimen showed significant synergy over AmB alone in the brain, liver, kidneys, and lungs. AmB alone cured no mice of infections in more than two organs, whereas AmB in combination with IFN-gamma cured 55% of infections in three or more organs. These results indicate that IFN-gamma has therapeutic efficacy in severely immunodeficient animals, especially in combination with AmB. Significant synergistic activity was noted in all organs except the spleen. Overall, IFN-gamma has utility as an adjunctive therapy against systemic cryptococcosis in the severely immunocompromised host.

Development of a Selective Medium for Isolation of Helicobacter pylori from Cattle and Beef Samples

Helicobacter pylori has been isolated from the human stomach with media containing only minimal selective agents. However, current research on the transmission and sources of infection requires more selective media due to the higher numbers of contaminants in environmental, oral, and fecal samples. The objective of this study was to develop and evaluate detection techniques that are sufficiently selective to isolate H. pylori from potential animal and food sources. Since H. pylori survives in the acidic environment of the stomach, low pH with added urea was studied as a potential selective combination. H. pylori grew fairly well on H. pylori Special Peptone plating medium supplemented with 10 mM urea at pH 4. 5, but this pH did not sufficiently inhibit the growth of contaminants. Various antibiotic combinations were then compared, and a combination consisting of 10 mg of vancomycin per liter, 5 mg of amphotericin B per liter, 10 mg of cefsulodin per liter, 62,000 IU of polymyxin B sulfate per liter, 40 mg of trimethoprim per liter, and 20 mg of sulfamethoxazole per liter proved to be highly selective but still allowed robust colonies of H. pylori to grow. This medium was highly selective for recovering H. pylori from cattle and beef samples, and it is possible that it could be used to enhance the recovery of this bacterium from human and environmental samples, which may be contaminated with large numbers of competing microorganisms.

Safety, tolerance, and pharmacokinetics of a small unilamellar liposomal formulation of amphotericin B (AmBisome) in neutropenic patients.

The safety, tolerance, and pharmacokinetics of a small unilamellar liposomal formulation of amphotericin B (AmBisome) administered for empirical antifungal therapy were evaluated for 36 persistently febrile neutropenic adults receiving cancer chemotherapy and bone marrow transplantation. The protocol was an open-label, sequential-dose-escalation, multidose pharmacokinetic study which enrolled a total of 8 to 12 patients in each of the four dosage cohorts. Each cohort received daily doses of either 1.0, 2.5, 5.0, or 7.5 mg of amphotericin B in the form of AmBisome/kg of body weight. The study population consisted of patients between the ages of 13 and 80 years with neutropenia (absolute neutrophil count, <500/mm3) who were eligible to receive empirical antifungal therapy. Patients were monitored for safety and tolerance by frequent laboratory examinations and the monitoring of infusion-related reactions. Efficacy was assessed by monitoring for the development of invasive fungal infection. The pharmacokinetic parameters of AmBisome were measured as those of amphotericin B by high-performance liquid chromatography. Noncompartmental methods were used to calculate pharmacokinetic parameters. AmBisome administered as a 1-h infusion in this population was well tolerated and was seldom associated with infusion-related toxicity. Infusion-related side effects occurred in 15 (5%) of all 331 infusions, and only two patients (5%) required premedication. Serum creatinine, potassium, and magnesium levels were not significantly changed from baseline in any of the dosage cohorts, and there was no net increase in serum transaminase levels. AmBisome followed a nonlinear dosage relationship that was consistent with reticuloendothelial uptake and redistribution. There were no breakthrough fungal infections during empirical therapy with AmBisome. AmBisome administered to febrile neutropenic patients in this study was well tolerated, was seldom associated with infusion-related toxicity, was characterized by nonlinear saturation kinetics, and was effective in preventing breakthrough fungal infections.

Superior efficacy of liposomal amphotericin B with prolonged circulation in blood in the treatment of severe candidiasis in leukopenic mice.

In leukopenic mice with severe systemic candidiasis, single-dose treatment (5 mg of amphotericin B [AMB]/kg of body weight) with long-circulating polyethylene glycol-coated AMB liposomes (PEG-AMB-LIP) resulted in zero mortality and a significant reduction in the number of viable Candida albicans in the kidney, whereas 70% mortality was seen in mice treated with five daily doses of AmBisome (5 mg of AMB/kg . day). When the first of five daily doses of AmBisome was combined with a single low dose of Fungizone (0.1 mg of AMB/kg), the efficacy was equal to that of PEG-AMB-LIP.

Fungal hepatic abscesses: characterization and management

Hepatic abscesses are being recognized with increasing frequency in immunocompromised patients and those with malignant diseases. Risk factors and treatment for patients with pure fungal abscesses and mixed fungal and pyogenic abscesses have not been well described. A retrospective review of patients with hepatic abscesses was undertaken at The Johns Hopkins Hospital from 1973 through 1993. Eight patients with pure fungal hepatic abscesses and 34 patients with mixed fungal/pyogenic abscesses were identified. Clinical presentation, diagnosis, management, and outcome were analyzed. In the group with pure fungal abscesses, fungemia was predictive of death; four patients in this group died, whereas the remaining four patients who received amphotericin B treatment before the onset of fungemia all survived. In the group with mixed fungal/pyogenic abscesses, 11 patients received amphotericin B, whereas 23 did not. Ten (43%) of these 23 patients died. However, only one of five patients who received more than 1000 mg of amphotericin B died. In patients with hematologic malignancies, who are known to be at risk for fungal infections, amphotericin B treatment should be instituted early. In patients with mixed fungal/pyogenic hepatic abscesses who fail to improve after drainage and broad-spectrum antibiotics, antimycotic therapy should be considered early, before the onset of fungemia.

Fungal hepatic abscesses: Characterization and management.

Hepatic abscesses are being recognized with increasing frequency in immunocompromised patients and those with malignant diseases. Risk factors and treatment for patients with pure fungal abscesses and mixed fungal and pyogenic abscesses have not been well described. A retrospective review of patients with hepatic abscesses was undertaken at The Johns Hopkins Hospital from 1973 through 1993. Eight patients with pure fungal hepatic abscesses and 34 patients with mixed fungal/pyogenic abscesses were identified. Clinical presentation, diagnosis, management, and outcome were analyzed. In the group with pure fungal abscesses, fungemia was predictive of death; four patients in this group died, whereas the remaining four patients who received amphotericin B treatment before the onset of fungemia all survived. In the group with mixed fungal/pyogenic abscesses, 11 patients received amphotericin B, whereas 23 did not. Ten (43%) of these 23 patients died. However, only one of five patients who received more than 1000 mg of amphotericin B died. In patients with hematologic malignancies, who are known to be at risk for fungal infections, amphotericin B treatment should be instituted early. In patients with mixed fungal/pyogenic hepatic abscesses who fail to improve after drainage and broad-spectrum antibiotics, antimycotic therapy should be considered early, before the onset of fungemia.

Deposition of amphotericin B aerosols in pulmonary aspergilloma.

The aim of the present study was to characterize amphotericin B aerosols nebulized by ultrasonic and jet nebulizers and to study their deposition and pharmacokinetics in patients with pulmonary mycetoma. The aerodynamic behaviour and pulmonary deposition of amphotericin B particles were measured using a direct isotopic method based on stable labelling of the drug with 99mTc. Each nebulizer was bench tested for inhaled mass and particle size distribution. Three patients suffering from pulmonary aspergilloma were enrolled for a 4 week clinical study. They received 5 mg of amphotericin B daily delivered by either Fisoneb or DP100 (ultrasonic) or Respirgard II (jet) nebulizers. Deposition of radiolabelled amphotericin B was measured once with each nebulizer using a gamma-camera. In two patients, amphotericin B serum concentration was monitored over a 330 min period after the nebulization had been completed. Inhaled masses of the three nebulizers, assessed as % of labelled drug caught in inspiratory filter in duplicate experiments, were: 5.8 and 3.6% for Respirgard II; 26.5 and 28.3% with Fisoneb; 5.9 and 6.3% for DP100. Mass median aerodynamic diameter (mean +/- SD) results were: 0.28 +/- 0.04 micron with Respirgard II; 4.82 +/- 0.78 microns with Fisoneb; and 2.27 +/- 1.14 microns with DP100. Because of larger particles and significantly greater inhaled mass, Fisoneb delivered more amphotericin B to the central airways, the lung periphery and in the mycetoma lung regions. Amphotericin B serum concentrations correlated with pulmonary deposition and remained below 25 ng.mL-1. No untoward effects were reported by the patients during the 4 week trial.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of escalating doses of liposomal amphotericin B (AmBisome) against hematogenous Candida lusitaniae and Candida krusei infection in neutropenic mice

Immunosuppressed CF1 mice were infected intravenously with two strains of Candida krusei and four strains of Candida lusitaniae (two of which were resistant to amphotericin B). Mice were treated with 1 or 2 mg of amphotericin B desoxycholate per kg of body weight per day or escalating doses of liposomal amphotericin B (8 to 30 mg/kg/day) or were left untreated. Higher doses of liposomal amphotericin B were as effective as standard dose of amphotericin B desoxycholate in prolonging survival but were significantly more effective in reducing the fungal burden in the kidneys of animals infected with both C. krusei strains and the C. lusitaniae strains that were susceptible to amphotericin B desoxycholate. This advantage of liposomal amphotericin B therapy could not be demonstrated in mice infected with the C. lusitaniae strains that were resistant to amphotericin B desoxycholate.