Autochthonous case of Trichophyton indotineae in Kuwait.

Trichophyton indotineae is an emerging dermatophyte that has remarkable impact on public health worldwide. In addition to producing severe extensive skin lesions, this species is frequently resistant to terbinafine, used as a first line agent. As a result, the infection is often refractory, making treatment very challenging. The current report describes the first case of Trichophyton indotineae infection in Kuwait. The infected woman had no recent travel history. She failed to respond to several courses of antifungals, but finally responded to voriconazole. The report suggests that T. indotineae is under recognised, hence, active surveillance of dermatophytes is warranted.

First Report of Azole-Resistant Aspergillus fumigatus with TR46/Y121F/T289A Mutations in Kuwait and an Update on Their Occurrence in the Middle East.

Pulmonary aspergillosis is a common fungal infection with several clinical manifestations including invasive, allergic and chronic chest diseases. Invasive pulmonary aspergillosis (IPA) is a leading cause of death in immunocompromised patients, particularly those receiving chemotherapy and among bone marrow transplant recipients. Aspergillus fumigatus is the most prevalent causative agent and voriconazole is the first-line therapy for IPA. In this study, we report the first isolation of voriconazole-resistant A. fumigatus carrying TR46/Y121F/T289A mutations from an immunocompromised pregnant lady in Kuwait. The patient was successfully treated for a probable respiratory infection with caspofungin and voriconazole. The literature review from PubMed has identified itraconazole-resistant clinical and environmental A. fumigatus isolates with TR34/L98H mutations in the cyp51A from several Middle Eastern countries including Kuwait. However, clinical A. fumigatus isolates with cyp51A TR46/Y121F/T289A mutations have not been reported previously from any country in the region while environmental isolates have been reported only from Iran. The source of voriconazole-resistant A. fumigatus CYP51A TR46/Y121F/T289A mutant in our patient remained unknown. Surveillance for azole resistance among clinical and environmental isolates of A. fumigatus is warranted in Kuwait.

Fatal Breakthrough Candidemia in an Immunocompromised Patient in Kuwait Due to Candida auris Exhibiting Reduced Susceptibility to Echinocandins and Carrying a Novel Mutation in Hotspot-1 of FKS1.

Candida auris is an emerging yeast pathogen that has recently caused major outbreaks in healthcare facilities worldwide. Clinical C. auris isolates are usually resistant to fluconazole and readily develop resistance to echinocandins and amphotericin B (AMB) during treatment. We describe here an interesting case of C. auris infection in an immunocompromised patient who had previously received AMB and caspofungin treatment. Subsequently, C. auris was isolated from tracheal (tracheostomy) secretions and twice from urine and all three isolates were susceptible to AMB and micafungin. The patient received a combination therapy with AMB and caspofungin. Although the C. auris was cleared from the urine, the patient subsequently developed breakthrough candidemia and the bloodstream isolate exhibited a reduced susceptibility to micafungin and also showed the presence of a novel (S639T) mutation in hotspot-1 of FKS1. Interestingly, C. auris from the tracheal (tracheostomy) secretions recovered one and four days later exhibited a reduced susceptibility to micafungin and S639Y and S639T mutations in hotspot-1 of FKS1, respectively. Although the treatment was changed to voriconazole, the patient expired. Our case highlights a novel FKS1 mutation and the problems clinicians are facing to treat invasive C. auris infections due to inherent or developing resistance to multiple antifungal drugs and limited antifungal armamentarium.

Candida albicans Induces Foaming and Inflammation in Macrophages through FABP4: Its Implication for Atherosclerosis.

Atherosclerosis is a chronic degenerative disorder characterized by lipid-dense plaques and low-grade inflammation affecting arterial walls. Foamy macrophages are important in the formation of atherosclerotic plaques and the induction of low-grade inflammation. The presence of lipid-laden macrophages has occurred in infections caused by opportunistic pathogens. Candida albicans is the major cause of candidiasis in immunocompromised patients, including those with diabetes mellitus. However, the role played by C. albicans in macrophage foaming and the associated inflammation is poorly understood. We investigated whether C. albicans induces foaming along with inflammation in macrophages and, if so, by which mechanism(s). We incubated THP-1 macrophages with heat-killed C. albicans (HKCA). HKCA-induced lipid accumulation in macrophages along with increased expression of inflammatory markers, including CD11b and CD11c or expression and secretion of IL-1ß. HKCA also increased the expression of PPARγ, CD36, and FABP4 in macrophages. Mechanistically, we found that the foamy and inflammatory macrophage phenotype induced by HKCA requires FABP4 because disruption of FABP4 in macrophages either by chemical inhibitor BMS309404 or small interfering RNA (siRNA) abrogated foam cell formation and expression of inflammatory markers CD11b, CD11c, and IL-1ß. Furthermore, HKCA-treated macrophages displayed high expression and secretion of MMP-9. Inhibition of FABP4 resulted in suppression of HCKA-induced MMP-9 production. Overall, our results demonstrate that C. albicans induces foam cell formation, inflammation, and MMP-9 expression in macrophages via the upregulation of FABP4, which may constitute a novel therapeutic target for treating C. albicans-induced atherosclerosis.

Epidemiology of Candidemia in Kuwait: A Nationwide, Population-Based Study.

The Candida species cause a majority of invasive fungal infections. In this article, we describe the nationwide epidemiology of candidemia in Kuwait in 2018. Yeast bloodstream isolates submitted from all major hospitals and identified by phenotypic MALDI-TOF MS and/or by molecular methods were studied. Susceptibility testing was performed by Etest. Out of 313 bloodstream yeasts, 239 Candida spp. isolates (excluding duplicate isolates) were obtained during 234 candidemic episodes among 223 patients. Mixed-species candidemia and re-infection occurred in 5 and 11 patients, respectively. C. albicans (n = 74), C. parapsilosis (n = 54), C. tropicalis (n = 35), C. auris (n = 33), C. glabrata (n = 32), other Candida spp. (n = 11), and other yeasts (n = 9) caused fungemia. Nearly 50% of patients were in intensive care units. Candida spp. isolates (except C. glabrata) were susceptible to caspofungin and 27% of C. auris were amphotericin B-resistant. Resistance to fluconazole was 100% in C. auris, 17% in C. parapsilosis, 12% in C. glabrata, and 1% in C. albicans. Mortality was 47% for other Candida/yeast infections. Nationwide candidemia incidence in 2018 was 5.29 cases/100,000 inhabitants. Changes in species spectrum, increasing fluconazole resistance in C. parapsilosis, and the emergence of C. auris as a major pathogen in Kuwait are noteworthy findings. The data could be of help in informing decisions regarding planning, in the allocation of resources, and in antimicrobial stewardship.

Disseminated Rhinocladiella mackenziei infection in a kidney transplant recipient: A case report and literature review.

Rhinocladiella mackenziei is a rare fungal pathogen which belongs to a large group of pigmented fungi causing phaeohyphomycosis. R. mackenziei primarily infects the brain and leads to high fatality rates among both immunocompetent and immunocompromised individuals. Among solid organ transplant recipients, the infection may disseminate to extra-neuronal sites, necessitating comprehensive radiologic imaging. Here we describe a new case of R. mackenziei infection in a renal transplant patient involving the brain and renal allograft. She received liposomal amphotericin B and voriconazole but no surgical intervention. Ultimately, the patient died after two months of hospital stay. A review of all reported cases of transplant patients infected with R. mackenziei is also presented.

Pulmonary aspergillosis in two COVID-19 patients from Kuwait.

Critically ill patients with coronavirus disease 2019 (COVID-19) are at risk of invasive pulmonary aspergillosis. The clinical manifestations of a superimposed fungal infection in those patients are difficult to underpin. This is compounded by the non-specific radiological findings associated with this infection and the challenges associated with performing bronchoscopy in COVID-19 patients. We would like to present two COVID-19 cases who developed secondary Aspergillus pulmonary infection in the intensive care unit as shown by respiratory cultures, serum galactomannan and radiological images. Despite advanced intensive care and use of antifungal agents, both patients died eventually. This report illustrates the negative impact of secondary Aspergillosis and calls for the need of increased awareness of COVID19-associated pulmonary aspergillosis.

First Isolation of Candida nivariensis, an Emerging Fungal Pathogen, in Kuwait.

OBJECTIVE: C. nivariensis is a rare Candida species which is phenotypically closely related to Candida glabrata and Candida bracarensis. The 3 species form the C. glabrata sensu lato complex. Here, we describe the first isolation and characterization of a C. nivariensis isolate cultured from the tracheal aspirate obtained from a young man in Kuwait. MATERIALS AND METHODS: The yeast isolate was initially tested by VITEK 2 followed by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and multiplex PCR. The identification was confirmed by sequencing of internal transcribed spacer (ITS) region of rDNA. Antifungal susceptibility testing was performed by Etest, and phylogenetic comparison with other international strains was carried out by using MEGA version 7 software. RESULTS: The C. nivariensis isolate was misidentified by VITEK 2, but correctly identified by MALDI-TOF MS with updated software and multiplex PCR. The identity was confirmed by sequence comparisons of ITS region of rDNA. Antifungal susceptibility testing revealed high minimum inhibitory concentration (MIC) against fluconazole, but low MICs against amphotericin B and echinocandins. Phylogenetically, our isolate was closely related to Indian isolates. CONCLUSIONS: This report extends the geographic distribution of C. nivariensis to the Arabian Peninsula. MALDI-TOF MS with updated software and molecular tests are needed to correctly identify C. nivariensis. Since C. nivariensis may exhibit reduced susceptibility to antifungal agents, accurate identification and antifungal susceptibility testing are essential, particularly for isolates from sterile sites, for optimal patient management.

Influenza-associated pulmonary aspergillosis in a patient on ECMO.

Invasive pulmonary aspsergillosis (IPA) is a well-known disease typically affecting severely immunocompromised patients. Recently, IPA has been described in a new group of patients such as those infected with influenza. In this report, we would like to present a case of pulmonary aspergillosis following influenza infection for the first time in Kuwait, and raise awareness about such unrecognized threatening co-infection.

Magnusiomyces capitatus fungemia: The value of direct microscopy in early diagnosis.

Two cases of fungemia caused by Magnusiomyces capitatus, an arthroconidial yeast-like fungus, in non-hematologic immunocompromised patients are described. Both patients died before definite diagnosis of M. capitatus was made. The report highlights that pending confirmation of the isolate by phenotypic and/or molecular methods, the characteristic morphologic features observed in Gram-stained smears of blood culture positive bottles can lead to early preliminary diagnosis, thus significantly reducing time required for initiating appropriate antifungal therapy.

Non-typhoidal Salmonella blood stream infection in Kuwait: Clinical and microbiological characteristics.

Non-typhoidal Salmonella (NTS) bacteremia is a significant cause of morbidity and mortality worldwide. It is considered to be an emerging and neglected tropical disease in Africa. We studied this in two tertiary hospitals-Al Farwaniya and Al Amiri-in Kuwait, a subtropical country, from April 2013-May 2016. NTS bacteremia was present in 30 of 53,860 (0.75%) and 31 of 290,36 (1.33%) blood cultures in the two hospitals respectively. In Al Farwaniya hospital, one-third of the patients were from some tropical developing countries of Asia. About 66% of all patients (40/61) had diarrhea, and of these, 65% had the corresponding blood serovar isolated from stool culture. A few patients had Salmonella cultured from urine. Patients were either young or old. Most of the patients had co-morbidities affecting the immune system. Two patients each died in both hospitals. The number of different serovars cultured in each hospital was 13, and most infections were due to S. Enteritidis (all sequence type [ST]) 11) and S. Typhimurium (all ST19) except in a subgroup of expatriate patients from tropical developing countries in Al Farwaniya hospital. About a quarter of the isolates were multidrug-resistant. Most patients were treated with a cephalosporin with or without other antibiotics. S. Enteritidis and S. Typhimurium isolates were typed by pulsed field-gel electrophoresis (PFGE) and a selected number of isolates were whole-genome sequenced. Up to four different clades were present by PFGE in either species. Whole-genome sequenced isolates showed antibiotic-resistance genes that showed phenotypic correlation, and in some cases, phenotypes showed absence of specific genes. Whole-genome sequenced isolates showed presence of genes that contributed to blood-stream infection. Phylogeny by core genome analysis showed a close relationship with S. Typhimurium and S. Enteritidis from other parts of the world. The uniqueness of our study included the finding of a low prevalence of infection, mortality and multidrug-resistance, a relatively high prevalence of gastrointestinal infection in patients, and the characterization of selected isolates of S. Typhimurium and S. Enteritidis serovars by whole-genome sequencing that shed light on phylogeny, virulence and resistance. Similarities with studies from developing countries especially Africa included infection in patients with co-morbidities affecting the immune system, predominance of S. Typhimurium and S. Enteritidis serovars and presence of drug-resistance in isolates.

Renal fungus ball in a patient with retroperitoneal fibrosis: Unique complication in a rare disease.

Candida fungus ball is a rare presentation of urinary tract infections among adult patients and is associated with considerable morbidity. Because clinical signs are not specific, diagnosis is often delayed. Furthermore, treatment is occasionally difficult, and the approach to such cases varies widely among different centers. In this report, we describe a patient with retroperitoneal fibrosis who developed a renal fungus ball. Management of this challenging case is discussed, and review of the literature is presented.