National Tuberculosis Reference Laboratory, Kuwait.To compare Genotype MTBDRplus (gMTBDR(+)), INNO-LiPA Rif.TB (INNO-LiPA), polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing for detecting rifampicin (RMP) and/or isoniazid (INH) resistance-associated mutations in the rpoB hot-spot region (HSR-rpoB), the katG codon 315 (katG315) and the inhA regulatory region (inhA-RR) among multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates.A total of 82 MDR-TB and 43 pansusceptible M.tuberculosis BACTEC 460-characterised isolates were processed using molecular techniques and the Mycobacterial Growth Indicator Tube (MGIT) 960 system.All susceptible strains contained wild-type sequences in target genes. RMP resistance was detected in respectively 78, 77 and 79 MDR-TB strains by gMTBDR(+), INNO-LiPA and HSR-rpoB sequencing. Two isolates with Ins514TTC mutation were detected as RMP-resistant by gMTBDR(+) but as RMP-susceptible by INNO-LiPA. One isolate with L533P mutation, detected as RMP-susceptible by gMTBDR(+), was detected as RMP-resistant by INNO-LiPA. Two of three isolates detected as RMP-susceptible by gMTBDR(+), INNO-LiPA, HSR-rpoB sequencing and the MGIT 960 system contained a I572F mutation that is outside HSR-rpoB. INH resistance was detected in respectively 76, 60, 60 and 22 MDR-TB strains by gMTBDR(+), katG315 PCR-RFLP, katG315 sequencing and inhA-RR sequencing.Although gMTBDR(+) accurately detected ∼ 88% of MDR-TB strains, some rpoB mutations were either missed or were outside the region of analysis of the gMTBDR(+) assay.
Sixteen end-stage renal disease patients who received hemodialysis for 2.9 years with no magnesium in the dialysate were evaluated for serum calcium, magnesium and parathyroid hormone (PTH) status. Eleven of these patients became hypomagnesemic with subnormal total and ultrafiltrable serum Mg concentrations (low-Mg group). The five remaining patients had consistently normal serum Mg concentrations (normal-Mg group). All had normal total and ionized serum Ca. However, the total and ionized serum Ca levels in the low-Mg group were significantly lower than those of the normal-Mg group. Within 2 weeks of Mg repletion (by dialysis against 0.25 mMof Mg), the N-terminal PTH, total and ultrafiltrable serum Mg, and the total and ionized serum Ca increased in the low-Mg group. There was a strong negative correlation between initial serum Mg and the percent change in N-terminal PTH (r = -0.833) at 2 weeks for all patients. There was also a strong positive correlation between initial ionized Ca and total serum Mg for all patients (r = 0.774). Mg repletion decreased the incidence of cramps experienced during dialysis by all patients. These data suggest that Mg-free dialysis in some patients can cause Mg depletion, which is symptomatic and which may suppress the parathyroid gland.
The original publication of this article [1] contained few erroneous paragraphs and errors in Table 1 and Table 2. The first four paragraphs are in the ‘Results’ section while the last four paragraphs are in the ‘Discussion’ section. The errors in Table 1 involve the number of isolates tested for pyrazinamide and pyrazinamide susceptible isolates, ethambutol-susceptible isolates with a mutation and number of resistant isolates with a mutation for streptomycin. The error in Table 2 involves wrong codon number for a mutation in isolate KM17-01 in Cluster XII for gidB gene. The updated informations have been indicated in bold and also refer corrected Tables 1 and 2.
Candida auris, a recently recognized, often multidrug-resistant yeast, has become a significant fungal pathogen due to its ability to cause invasive infections and outbreaks in healthcare facilities which have been difficult to control and treat. The extraordinary abilities of C. auris to easily contaminate the environment around colonized patients and persist for long periods have recently resulted in major outbreaks in many countries. C. auris resists elimination by robust cleaning and other decontamination procedures, likely due to the formation of ‘dry’ biofilms. Susceptible hospitalized patients, particularly those with multiple comorbidities in intensive care settings, acquire C. auris rather easily from close contact with C. auris-infected patients, their environment, or the equipment used on colonized patients, often with fatal consequences. This review highlights the lessons learned from recent studies on the epidemiology, diagnosis, pathogenesis, susceptibility, and molecular basis of resistance to antifungal drugs and infection control measures to combat the spread of C. auris infections in healthcare facilities. Particular emphasis is given to interventions aiming to prevent new infections in healthcare facilities, including the screening of susceptible patients for colonization; the cleaning and decontamination of the environment, equipment, and colonized patients; and successful approaches to identify and treat infected patients, particularly during outbreaks.
We previously reported that digoxin-like immunoreactive substance (DLIS) was found only in the blood of those dialysis patients who were hypertensive and had high systemic vascular resistance. In order to determine whether the DLIS was a marker for the natriuretic hormone, renal infusion studies were carried out in anesthetized dogs. When ultrafiltrates from patients with high blood DLIS levels were infused into the renal artery of one kidney there was a significant increase in the fractional excretion of sodium (FE Na) from its baseline value. Further, the FE Na of these kidneys were significantly higher than the FE Na noted for the contralateral kidneys which were simultaneously infused with ultrafiltrates obtained from dialysis patients lacking DLIS activity in their blood. We conclude that the DLIS is or represents a marker for natriuretic hormone. Since the natriuresis noted was independent of renal plasma flow and glomerular filtration rate and since the fractional excretion of potassium was not influenced by the infusion, we believe that DLIS is different from atrial natriuretic factor.
Abstract The interface of sound in general and music in particular has known and unknown dimensions in human physiology, human psychology and larger well-being of human health. Acoustic therapies and stimulation have been scientifically proven to have a powerful effect on the brain. Recent researches have shown that music can help in many aspects of the brain including pain reduction, stress relief, Seizure, Stroke, memory, and brain injuries. The intervention of sound or music as a type of treatment can be medicine less and mostly concentrates on selective sound frequencies or acoustic loops. In this paper an attempt is made to study the intervention of these sound frequencies in general and their effects on neuro-psychiatric mechanisms and allied phenomenon. The quantification of specific frequencies (Acoustic loops) which will ameliorate the various disorders after their identification can also be correlated with various biochemical parameters that will be analysed with regards to the changes effected by these interventions. The proposed research work might provide a novel approach of treatment for neuro psychiatric disorders using the above stated therapy. The work intends to provide the effect of this therapy on 50 patients/subjects which are taken in isolation wherein the results on selected subjects has been quite demanding. These patients have been already diagnosed with psychiatric disorders at SKIMS and are being re-accessed at NARC using Acoustic Loop Therapy. The proposed work will also provide a scaling or quantitative approach in the intervention of Neuro Acoustic disorders.
Objective: Nontuberculous mycobacteria (NTM) often cause disease that is clinically indistinguishable from tuberculosis. Specific identification is important as treatment varies according to Mycobacterium species causing the infection. This study used multiplex PCR (mPCR) assay for rapid differentiation of mycobacterial growth indicator tube 960 system (MGIT) cultures as Mycobacterium tuberculosis (MTB) or NTM together with INNO LiPA Mycobacteria v2 assay (LiPA) and/or PCR sequencing of rDNA for species-specific identification of selected MTB and all NTM isolates in Kuwait. Materials and Methods: DNA was extracted from MGIT cultures (n = 1,033) grown from 664 pulmonary and 369 extrapulmonary specimens from 1,033 suspected tuberculosis patients. mPCR was performed to differentiate MTB from NTM. LiPA was performed and results were interpreted according to kit instructions. rDNA was amplified and sequenced by using panmycobacterial primers. Results: mPCR identified 979 isolates as MTB, 53 as NTM and 1 isolate as mixed culture. LiPA and/or PCR sequencing confirmed 112 of 979 selected isolates as MTB. Mixed culture contained M. tuberculosis and M. fortuitum. LiPA yielded 12 patterns and identified 10 species/species complexes among 47 NTM, M. kansasii + M. scrofulaceum in one culture and 5 isolates only at genus level. PCR sequencing yielded more specific identification for 22 isolates at the species/subspecies level. Conclusions: mPCR rapidly differentiated MTB from NTM. LiPA identified 44 of 52 NTM isolates at the species/species complex level and 2 mixed cultures. PCR sequencing yielded more specific identification at the species/subspecies level. Rapid differentiation as MTB or NTM by mPCR, followed by species-specific NTM identification by LiPA/PCR sequencing is suitable for the proper management of mycobacterial infections in Kuwait.
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.
Candida glabrata is intrinsically less susceptible to azoles, and resistance to echinocandins and reduced susceptibility (RS) to amphotericin B (AMB) have also been detected. The molecular mechanisms of RS to AMB were investigated in C. glabrata strains in Kuwait by sequence analyses of genes involved in ergosterol biosynthesis. A total of 1,646 C. glabrata isolates were tested by Etest, and results for 12 selected isolates were confirmed by reference broth microdilution. PCR sequencing of three genes (ERG2, ERG6, and ERG11) was performed for all isolates with RS to AMB (RS-AMB isolates) and 5 selected wild-type C. glabrata isolates by using gene-specific primers. The total cell sterol content was analyzed by gas chromatography-mass spectrometry. The phylogenetic relationship among the isolates was investigated by multilocus sequence typing. Wild-type isolates contained only synonymous mutations in ERG2, ERG6, or ERG11, and the total sterol content was similar to that of the reference strains. A nonsynonymous ERG6 mutation (AGA48AAA, R48K) was found in both RS-AMB and wild-type isolates. Four RS-AMB isolates contained novel nonsense mutations at Trp286, Tyr192, and Leu341, and 2 isolates contained a nonsynonymous mutation in ERG6 (V126F or C198F); and the sterol content of these isolates was consistent with ERG6 deficiency. Two other RS-AMB isolates contained a novel nonsynonymous ERG2 mutation (G119S or G122S), and their sterol content was consistent with ERG2 deficiency. Of 8 RS-AMB isolates, 1 fluconazole-resistant isolate also contained nonsynonymous Y141H plus L381M mutations, while 7 isolates contained only synonymous mutations in ERG11 All isolates with ERG6, ERG2, and ERG11 mutations were genotypically distinct strains. Our data show that ERG6 and ERG2 are major targets conferring RS-AMB in clinical C. glabrata isolates.
