zithromax and Pythiosis

Pythium insidiosum causes a rare sight-threatening keratitis and is a devastating ocular pathology with a high morbidity. It is frequently mistaken as fungal keratitis. Here we highlight a rare case of pediatric Pythium insidiosum keratitis which was successfully managed using an antibiotic combination of linezolid and azithromycin with cyanoacrylate glue.. A 9-year-old young male child presented to our clinic with defective vision, pain, redness in the right eye for 5 days post stick injury. In the right eye, Snellen's best-corrected visual acuity (BCVA) was 6/12 which deteriorated to hand movements within 5 days of treatment. Ocular examination revealed 6 × 5 mm dry-looking mid stromal corneal infiltrate with feathery margin involving the visual axis. The clinical picture was suggestive of fungal keratitis. Corneal scraping and smear examination with 10% KOH and Gram stain revealed long slender hyaline hyphae with sparse septations. Before the culture result, the patient was started on 5% Natamycin and 1% Itraconazole hourly, but still, the infiltrate progressed. Further, P. Insidiosum keratitis was considered as the differential, which was confirmed on blood agar culture. After receiving culture results, the patient was managed with 0.2% Linezolid and 1% Azithromycin hourly. Due to the rapid progression of infiltrate, corneal melt, and younger age, cyanoacrylate glue, and bandage contact lens were used. On the last follow-up, the BCVA recovered to 6/12.. Prompt diagnosis, clinical awareness, and a specific treatment regime is needed for managing this devastating corneal entity. Cyanoacrylate glue due to its antibacterial properties can be a potential rescuer and can be considered for managing these cases.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Child; Corneal Ulcer; Cyanoacrylates; Eye Infections, Fungal; Humans; Keratitis; Linezolid; Male; Pythiosis; Pythium

Pythium, soil-borne plant pathogens, are in the class Oomycetes. They are not true fungi, but are related to diatom and algae. There are two human pathogens including P. insidiosum and P. aphanidermatum. To date, only one case of pythiosis caused by P. aphanidermatum has been reported. We present herein the first case of P. aphanidermatum vascular pythiosis in Asia.. A 47-year-old Thai woman, living in North Thailand, with ß thalassemia/hemoglobin E presented with acute recurrent arterial insufficiency of both legs. Emergent embolectomy with clot removal was performed. The pathology of the clot exhibited noncaseous granulomatous inflammation with many fungal hyphal elements. PCR identified P. aphanidermatum with 100% identity. Final diagnosis is vascular pythiosis. Unfortunately, the patient eventually expired after treatment with itraconazole, terbinafine, azithromycin, and doxycycline.. To date, only one case of pythiosis caused by P. aphanidermatum has been reported. We present herein the first case of P. aphanidermatum vascular pythiosis in Asia.

Topics: Antifungal Agents; Azithromycin; Fatal Outcome; Female; Host-Pathogen Interactions; Humans; Hyphae; Itraconazole; Middle Aged; Pythiosis; Pythium; Terbinafine; Thailand; Thrombosis

Pythium insidiosum infections have been widely studied in an attempt to develop an effective therapeutic protocol for the treatment of human and animal pythiosis. Several antifungal agents are still prescribed against this oomycete, although they present contradictory results. To evaluate the susceptibility profile and to verify the morphological alterations in P. insidiosum isolates treated with amorolfine hydrochloride and azithromycin, alone or in combination. Susceptibility tests for P. insidiosum isolates (n = 20) against amorolfine hydrochloride (AMR) and azithromycin (AZM) were performed according to Clinical and Laboratory Standards Institutes (CLSI) protocol M38-A2. Combinations of both drugs were evaluated using the checkerboard microdilution method. Additionally, transmission and scanning electron microscopy were performed in order to verify the morphological alterations in P. insidiosum isolates in response to these drugs. All P. insidiosum isolates had a minimum inhibitory concentration (MIC) ranging from 16 to 64 mg/l and 8 to 64 mg/l for amorolfine hydrochloride and azithromycin, respectively. Synergistic interactions between the drugs were not observed, with antagonism in 59.8% of isolates, and indifferent interactions in 36.2%. Electron microscopy showed changes in the surface of P. insidiosum hyphae, disorganization of intracellular organelles, and changes in the plasma membrane and cell wall of oomycetes treated with the drugs. This is the first study to demonstrate in vitro anti-P. insidiosum effect of amorolfine hydrochloride. These results indicate the therapeutic potential of this drug against cutaneous and subcutaneous forms of pythiosis, but further studies are necessary to confirm this potential.

Topics: Animals; Antifungal Agents; Azithromycin; Disease Models, Animal; Dogs; Horses; Humans; Microbial Sensitivity Tests; Morpholines; Pythiosis; Pythium

To describe the clinical features, microbiological profile, and outcome of a series of cases of Pythium keratitis treated with topical and oral linezolid and topical azithromycin eye drops.. This was a retrospective interventional case series of microbiologically and/or histopathologically proven cases of Pythium keratitis seen between October 2016 and December 2019. All patients received a combination of topical linezolid and/or azithromycin eye drops with oral linezolid. Analysis of demographic data, predisposing risk factors, microbiological results, treatment regimen, visual acuity, surgical intervention, and final outcome was performed. A subgroup analysis of cases >6 mm in size was performed. Success was defined as complete resolution on medical management. Failure was defined as worsening of infection necessitating therapeutic penetrating keratoplasty or evisceration.. Of 21 cases, 2 were lost to follow up, 1 was diagnosed on histopathology, and 1 received only topical linezolid. Characteristic microbiological features were noted on 10% potassium hydroxide calcofluor white wet mount in 20/21 (95.23%) and Gram stain in 18/21 (85.71%). On triple drug regimen, 14/17 cases (82.35%) resolved. Average time to resolution was 87.64 ± 44.44 days. More than 60% infiltrates (13/21) were large, and 66.66% infiltrates resolved in 109.3 ± 57.06 days. Of the 5 failures, 4 needed therapeutic keratoplasty and 1 needed evisceration. All grafts failed.. The dual topical drug regimen with oral linezolid has good cure rates (over 80%) for Pythium keratitis over prolonged duration. It is recommended to persevere with medical therapy even in large infiltrates because more than two thirds resolved.

Topics: Administration, Ophthalmic; Administration, Oral; Adolescent; Adult; Aged; Anti-Bacterial Agents; Azithromycin; Child; Drug Therapy, Combination; Eye Infections, Parasitic; Female; Humans; Keratitis; Linezolid; Male; Middle Aged; Ophthalmic Solutions; Pythiosis; Retrospective Studies; Treatment Outcome

Topics: Anti-Bacterial Agents; Antifungal Agents; Antiparasitic Agents; Azithromycin; Clarithromycin; Doxycycline; Humans; Itraconazole; Macrolides; Parasitic Sensitivity Tests; Pythiosis; Pythium; Terbinafine; Tetracyclines; Thailand

To report clinical profile and compare management options for Pythium keratitis.. Retrospective interventional study of 46 patients diagnosed as Pythium keratitis by PCR DNA sequencing from January 2014 to July 2017. Interventions were categorised into medical management (MM) (topical azithromycin and linezolid with oral azithromycin at presentation), surgery (S) (therapeutic penetrating keratoplasty, TPK), surgical adjunct (SA) (cryotherapy±alcohol with TPK) and medical adjunct (MA) (MM after TPK).. Primary treatment included MM (1 eye), SA (3 eyes) and S (42 eyes). Recurrence occurred in 27/43 eyes (MM+S group). Second surgery (S) was required in 11 eyes (TPK-2), with additional procedures (SA) in 10 eyes and evisceration in five eyes. 8/43 eyes received MA after TPK-1. One eye required TPK-3. Recurrence occured in all eyes that received MA (100%) and in 28 of 54 TPKs (51.8%) (TPK 1+2+3) in 42 eyes. Recurrence was noted in 1/14 (7.1%) that underwent SA.. The currently available and recommended treatment for Pythium keratitis is surgical by means of a TPK and in worse cases evisceration. In our study, MM/MA measures showed no benefit with recurrence or worsening of infection requiring resurgery. Almost 50% of TPKs had a recurrence requiring resurgery. However, adjunctive procedures during TPK appear to have additional benefit with low risk of recurrence and could be included as routine care.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Azithromycin; Child; Corneal Ulcer; DNA, Protozoan; Eye Infections, Parasitic; Female; Humans; Keratoplasty, Penetrating; Linezolid; Male; Middle Aged; Polymerase Chain Reaction; Pythiosis; Pythium; Retrospective Studies; Risk Factors; Treatment Outcome

We evaluated the efficacy of azithromycin (50 mg/kg, every 12 h [q12h] orally) and miltefosine (25 mg/kg, q24h orally) treatments in an experimental model of vascular/disseminated pythiosis in immunosuppressed mice. Azithromycin was the only treatment able to reduce mortality. The histopathological findings showed acute vascular inflammation, pathogen dissemination, necrotizing myositis, neuritis, and arteritis. The results suggest that azithromycin, but not miltefosine, may have clinical relevance in the treatment of vascular/disseminated pythiosis.

Topics: Animals; Antiprotozoal Agents; Azithromycin; Immunocompromised Host; Mice; Phosphorylcholine; Pythiosis; Pythium

Topics: Azithromycin; Child; Corneal Ulcer; Eye Infections, Fungal; Humans; Male; Pythiosis; Pythium; Treatment Outcome

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Bridged Bicyclo Compounds, Heterocyclic; Clarithromycin; Diterpenes; Humans; Josamycin; Linezolid; Macrolides; Oomycetes; Oxazolidinones; Phosphorylcholine; Pleuromutilins; Polycyclic Compounds; Pythiosis; Pythium

The oomycete

Topics: Acanthamoeba Keratitis; Anti-Bacterial Agents; Antifungal Agents; Azithromycin; Contact Lenses; Diagnosis, Differential; Humans; Injections, Intraocular; Male; Ophthalmic Solutions; Pythiosis; Voriconazole; Young Adult

To describe the previously unreported successful treatment of presumptive Pythium keratitis (PK) with medical therapy alone.. A 42-year-old female homemaker presented to us with a 15-day history of pain and redness in the right eye after a trivial injury. Her vision was 20/80 at presentation. Slit-lamp biomicroscopy revealed a central, dense and dry-looking, grayish-white infiltrate reaching mid stroma. The infiltrate had feathery margins and was surrounded by multiple tentacle-like lesions and peripherally expanding pinhead-sized subepithelial lesions. The contralateral eye was essentially normal. Diagnostic corneal scraping on smears revealed broad, aseptate, hyaline filaments with ribbon-like folds; very characteristic of Pythium species. Confocal imaging revealed fungal filaments. Based on corroborative evidence, a diagnosis of presumptive PK was made. She was administered a combination therapy consisting of eye drop linezolid 0.2% 1 hourly, azithromycin 1% 2 hourly, atropine sulfate 1% thrice daily, and oral azithromycin 500 mg once daily for 3 days in a week.. After initial worsening in the form of stromal expansion, regression of pinhead-sized lesions was seen with onset of scarring by as early as day 4 of intense medical therapy. The tentacle-like lesions did not worsen. On day 8, significant resolution was noted with scarring, and by the end of 2 weeks, the entire stromal lesion had scarred and complete resolution of expanding tentacles was observed in 3 weeks.. Presumptive Pythium keratitis of the patient completely resolved with antibacterial treatment alone. It is pertinent for ophthalmologists to be aware of this new treatment regimen.

Topics: Administration, Oral; Administration, Topical; Adult; Anti-Bacterial Agents; Atropine; Azithromycin; Drug Therapy, Combination; Eye Infections, Parasitic; Female; Humans; Keratitis; Linezolid; Mydriatics; Ophthalmic Solutions; Pythiosis; Pythium

The present study investigated the in vitro and the in vivo interactions among azithromycin, clarithromycin, minocycline, and tigecycline against Pythium insidiosum. In vitro antimicrobial activities were determined by the broth microdilution method in accordance with CLSI document M38-A2, and the antibiotic interactions were assayed using the checkerboard MIC format. In vivo efficacy was determined using a rabbit infection model. The geometric mean MICs of azithromycin, clarithromycin, minocycline, and tigecycline against P. insidiosum were, respectively, 1.91, 1.38, 0.91, and 0.79 μg/ml. By checkerboard testing, all combinations resulted in in vitro synergistic interactions (>60%). Antagonism was not observed. The in vivo studies showed that azithromycin (20 mg/kg/day twice daily) alone or in combination with minocycline (10 mg/kg/day twice daily) significantly decreased the fungal burden. This study demonstrates that azithromycin possesses potent curative efficacy against subcutaneous pythiosis in the rabbit model.

Topics: Animals; Antifungal Agents; Azithromycin; Clarithromycin; Drug Administration Schedule; Drug Synergism; Drug Therapy, Combination; Microbial Sensitivity Tests; Minocycline; Multivariate Analysis; Pythiosis; Pythium; Rabbits; Skin; Tigecycline

We describe here the in vitro activities of azithromycin, clarithromycin, minocycline, or tigecycline alone and in combination with amphotericin B, itraconazole, terbinafine, voriconazole, anidulafungin, caspofungin, or micafungin against 30 isolates of the oomycete Pythium insidiosum. The assays were based on the CLSI M38-A2 technique and the checkerboard microdilution method. The main synergisms observed were through the combination of minocycline with amphotericin B (73.33%), itraconazole (70%), and micafungin (70%) and of clarithromycin with micafungin (73.33%).

Topics: Animals; Antifungal Agents; Azithromycin; Clarithromycin; Drug Combinations; Drug Synergism; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Minocycline; Pythiosis; Pythium; Tigecycline