Miracle-dz/UniFAR-FTUs huggingface dataset:
High chloroquine treatment failure rates and predominance of mutant genotypes associated with chloroquine and antifolate resistance among falciparum malaria patients from the island of Car Nicobar, India.

OBJECTIVES An in vivo chloroquine efficacy study was undertaken on the island of Car Nicobar because a temporal rise in the Plasmodium falciparum parasite population containing mutations in the chloroquine resistance transporter (PfCRT) protein has been reported there. METHODS A WHO protocol with a 28 day follow-up schedule was used for chloroquine efficacy studies. Finger-prick blood from P. falciparum malaria patients was used for sequencing the genes encoding PfCRT (exon 2), dihydrofolate reductase (PfDHFR) and dihydropteroate synthetase (PfDHPS). RESULTS The majority of patients showed chloroquine treatment failure (60.42%, n=48). A higher early treatment failure (ETF) rate was recorded among non-responders (23 of 29, 79.31%). Each patient, irrespective of their chloroquine response, was infected with P. falciparum that contained mutated PfCRT (predominantly genotype C72V73I74E75T76) associated with high chloroquine resistance and none with the wild-type pfcrt gene. Therefore, mutated PfCRT was also present in the P. falciparum isolates of all the chloroquine responders. The majority of individuals from both groups also contained parasites with a high number of two-locus PfDHFR-PfDHPS mutations, associated with a high level of antifolate resistance. CONCLUSIONS There is a predominance of chloroquine- and antifolate-resistant P. falciparum malaria in Car Nicobar, requiring an alternative antimalarial drug treatment policy, such as implementation of artesunate combination therapy (ACT), for this island.
Evaluating the stability of colistin and colistin methanesulphonate in human plasma under different conditions of storage.

OBJECTIVES The purpose of this study was to assess the stability of colistin and colistin methanesulphonate (CMS) in human plasma under storage conditions typically used in clinical pharmacokinetic (PK) and PK/pharmacodynamic (PD) investigations. METHODS Human plasma (pH adjusted to 7.4) containing colistin (2 mg/L) or CMS (2 or 30 mg/L) was stored at -20, -70 or -80 degrees C for 6-12 months. At periodic intervals, the concentrations of colistin in colistin-spiked samples, and of CMS and formed colistin in CMS-spiked samples, were analysed (n = 3 replicates at each time) by HPLC. RESULTS The time course of colistin concentrations in colistin-spiked plasma showed a substantially better stability at -80 and -70 degrees C than at -20 degrees C. With regard to CMS-spiked plasma of 2 and 30 mg/L stored at -80 and -70 degrees C, no quantifiable colistin formed over a 4 month period. However, the plasma spiked to 2 mg/L stored at -20 degrees C showed a substantial concentration of colistin ( approximately 0.4 mg/L) within 2 months. At all three storage temperatures, the stability of CMS was substantially better for the plasma spiked to contain 30 mg/L as compared with 2 mg/L. CONCLUSIONS The results of our long-term stability study have significant implications for those involved in conducting clinical PK and PK/PD studies with CMS/colistin.
RAHN-2, a chromosomal extended-spectrum class A beta-lactamase from Rahnella aquatilis.

OBJECTIVES Rahnella aquatilis is an environmental enterobacterial species with a chromosomal bla(RAHN-1) gene encoding extended-spectrum class A beta-lactamase RAHN-1. We describe the diversity of bla(RAHN) genes from two groups of strains, G1 and G2, isolated from raw fruits and vegetables, and the new class A beta-lactamase RAHN-2. METHODS MICs were determined by Etest. bla(RAHN) genes were amplified by PCR, sequenced, and cloned to produce RAHN-1 and RAHN-2 proteins whose kinetic parameters were determined. RESULTS All strains had similar beta-lactam resistance patterns. However, isolates of G1 were at least 2-fold more susceptible to piperacillin, amoxicillin, piperacillin/clavulanic acid, piperacillin/tazobactam and cefotaxime. Sequences of bla(RAHN) from G1 had <82.9% identity with that of bla(RAHN-1), whereas those of G2 were >92% identical. The RAHN-2 beta-lactamase was 89.8% identical to RAHN-1, 5-fold more efficient than RAHN-1 in hydrolysing ticarcillin and 2.5-fold more efficient in cefotaxime and cefuroxime hydrolysis. However, the specific activity of RAHN-1 was 2-fold higher than that of RAHN-2 suggesting that the bla(RAHN) genes are regulated differently. CONCLUSIONS The new class A beta-lactamase RAHN-2 is phenotypically difficult to detect and requires MIC determination.
Addressing the High Costs of Pancreaticoduodenectomy at Safety-Net Hospitals.

Importance Safety-net hospitals care for vulnerable patients, providing complex surgery at increased costs. These hospitals are at risk due to changing health care reimbursement policies and demand for better value in surgical care. Objective To model different techniques for reducing the cost of complex surgery performed at safety-net hospitals. Design, Setting, and Participants Hospitals performing pancreaticoduodenectomy (PD) were queried from the University HealthSystem Consortium database (January 1, 2009, to December 31, 2013) and grouped according to safety-net burden. A decision analytic model was constructed and populated with clinical and cost data. Sensitivity analyses were then conducted to determine how changes in the management or redistribution of patients between hospital groups affected cost. Main Outcomes and Measures Overall cost per patient after PD. Results During the 5 years of the study, 15 090 patients underwent PD. Among safety-net hospitals, low-burden hospitals (LBHs), medium-burden hospitals (MBHs), and high-burden hospitals (HBHs) treated 4220 (28.0%), 9505 (63.0%), and 1365 (9.0%) patients, respectively. High-burden hospitals had higher rates of complications or comorbidities and more patients with increased severity of illness. Perioperative mortality was twice as high at HBHs (3.7%) than at LBHs (1.6%) and MBHs (1.7%) (P < .001). In the base case, when all clinical and cost data were considered, PD at HBHs cost $35 303 per patient, 30.1% and 36.2% higher than at MBHs ($27 130) and LBHs ($25 916), respectively. Reducing perioperative complications or comorbidities by 50% resulted in a cost reduction of up to $4607 for HBH patients, while reducing mortality rates had a negligible effect. However, redistribution of HBH patients to LBHs and MBHs resulted in significantly more cost savings of $9155 per HBH patient, or $699 per patient overall. Conclusions and Relevance Safety-net hospitals performing PD have inferior outcomes and higher costs, and improving perioperative outcomes may have a nominal effect on reducing these costs. Redirecting patients away from safety-net hospitals for complex surgery may represent the best option for reducing costs, but the implementation of such a policy will undoubtedly meet significant challenges.
The Impact of Motivational Interviewing in Reducing Plaque and Bleeding Indices on Probing in Adult Users of the Family Health Strategy

Objective: To evaluate the impact of motivational interviewing (MI) in reducing plaque and bleeding indices on probing in adult users of the Family Health Strategy (FHS) with periodontal problems. Material and Methods: The study included 68 adult users searching for dental treatment in a family health unit located in Piracicaba, SP, and who had plaque index expressed in percentage greater than or equal to 40% and bleeding on probing greater than 10%. They were randomly divided into control group (CG), which received standard dental care and traditional oral health education and experimental group (EG), which received the same care of CG accompanied by the ME technique. Psycho-cognitive and clinical information of individuals were collected in both groups, such as self-assessment and self-efficacy in oral health, plaque index and gingival bleeding at baseline and at the end of treatment. Data were analyzed using Chi-square and Fisher tests and mixed repeated measures considering the significance level of 5% models. Results: We observed statistically significant differences in the 'oral health behavior' 'perception of oral health', 'self-efficacy for oral care', and ‘gingival bleeding index' variables on baseline and follow up the impact of the programs. Conclusion: Both strategies had an impact on psycho-cognitive and clinical oral aspects of FHU users; however, MI showed better results.
False extended-spectrum {beta}-lactamase phenotype in clinical isolates of Escherichia coli associated with increased expression of OXA-1 or TEM-1 penicillinases and loss of porins.

OBJECTIVES Two clinical isolates of Escherichia coli, EC18 and EC21, were non-susceptible (MICs 4-16 mg/L) to cefpirome and cefepime, with marked synergy with clavulanate, yet were susceptible to cefotaxime and ceftazidime (MICs ≤ 1 mg/L). EC19, from the same patient as EC21, was susceptible to all four cephalosporins. We sought to characterize the molecular basis of resistance in isolates EC18 and EC21. METHODS PFGE was used to study the genetic relationships of the isolates, and MICs were determined. β-Lactamases were characterized by PCR, isoelectric focusing (IEF), construction of genomic libraries and sequencing. A double mutant of E. coli J53 was constructed, lacking OmpC and OmpF porins. Plasmids from clinical isolates were transformed into E. coli J53 and J53ΔompCF. Outer membrane proteins (OMPs) were analysed by SDS-PAGE and OmpA by matrix-assisted laser desorption ionization time-of-flight/time-of-flight mass spectrometry. Expression of omp and bla genes was analysed by RT-PCR. RESULTS Isolates EC19 and EC21 had identical PFGE profiles, whereas EC18 was distinct. PCR and IEF confirmed β-lactamases with pIs of 5.4 (TEM-1) in EC18 and 7.4 (OXA-1) in both EC19 and EC21. EC18 had bla(TEM-1b) with the strong promoter P5 and lacked OmpC and OmpF. RT-PCR showed stronger expression of bla(OXA-1) in EC21 versus EC19, along with diminished expression of OmpC, though with increased OmpF. Plasmids extracted from EC18 and EC21 conferred increased MICs of cefpirome and cefepime, although susceptibility to cefotaxime and ceftazidime was retained. CONCLUSIONS The 'cefpiromase' or 'cefepimase' ESBL phenotype of the clinical isolates non-susceptible to cefpirome and cefepime resulted from high expression of TEM-1 or OXA-1 β-lactamases combined with loss of porins.
Acinetobacter baumannii isolates from pets and horses in Switzerland: molecular characterization and clinical data.

OBJECTIVES We investigated whether Acinetobacter baumannii isolates of veterinary origin shared common molecular characteristics with those described in humans. METHODS Nineteen A. baumannii isolates collected in pets and horses were analysed. Clonality was studied using repetitive extragenic palindromic PCR (rep-PCR) and multilocus sequence typing (MLST). PCR and DNA sequencing for various β-lactamase, aminoglycoside-modifying enzyme, gyrA and parC, ISAba1 and IS1133, adeR and adeS of the AdeABC efflux pump, carO porin and class 1/2/3 integron genes were performed. RESULTS Two main clones [A (n = 8) and B (n = 9)] were observed by rep-PCR. MLST indicated that clone A contained isolates of sequence type (ST) ST12 (international clone II) and clone B contained isolates of ST15 (international clone I). Two isolates of ST10 and ST20 were also noted. Seventeen isolates were resistant to gentamicin, 12 to ciprofloxacin and 3 to carbapenems. Isolates of ST12 carried bla(OXA-66), bla(ADC-25), bla(TEM-1), aacC2 and IS1133. Strains of ST15 possessed bla(OXA-69), bla(ADC-11), bla(TEM-1) and a class 1 integron carrying aacC1 and aadA1. ISAba1 was found upstream of bla(ADC) (one ST10 and one ST12) and/or bla(OXA-66) (seven ST12). Twelve isolates of different STs contained the substitutions Ser83Leu in GyrA and Ser80Leu or Glu84Lys in ParC. Significant disruptions of CarO porin and overexpressed efflux pumps were not observed. The majority of infections were hospital acquired and in animals with predisposing conditions for infection. CONCLUSIONS STs and the molecular background of resistance observed in our collection have been frequently described in A. baumannii detected in human patients. Animals should be considered as a potential reservoir of multidrug-resistant A. baumannii.
Medicaid Managed Care and Infant Health: A National Evaluation

In this study, we examine the effects of Medicaid managed care (MMC) on prenatal care utilization and infant health. We obtain separate estimates of the effect of primary care case management (PCCM) managed care programs and HMO managed care plans on prenatal care utilization, birth weight, and cesarean section. The results suggest the following: MMC was associated with a small, clinically unimportant decrease in the number of prenatal care visits; MMC had no statistically significant relationship to the APNCU index of the adequacy of prenatal care; MMC was associated with a significant increase in the incidence of low-birth weight and pre-term birth; and MMC had no association with the incidence of cesarean section. We argue that a causal interpretation of the first and third findings is unsupported by a careful reading of the evidence, and we conclude that Medicaid managed care had virtually no causal effect on, prenatal care use, birth outcomes, and cesarean section.
Dissemination of IMP-6 metallo-β-lactamase-producing Pseudomonas aeruginosa sequence type 235 in Korea.

OBJECTIVES To investigate the epidemiological traits of Pseudomonas aeruginosa clinical isolates producing metallo-β-lactamases (MBLs) in Korea. METHODS A total of 386 non-duplicate P. aeruginosa clinical isolates were collected from Korea in 2009. Detection of MBL genes was performed by PCR. The genetic organization of class 1 integrons carrying the MBL gene cassette was investigated by PCR mapping and sequencing. The epidemiological relationships of the isolates were investigated by multilocus sequence typing and PFGE. RESULTS Of 386 P. aeruginosa isolates, 30 (7.8%) isolates carried the bla(IMP-6) gene and 1 (0.3%) isolate carried the bla(VIM-2) gene. A probe specific for the bla(IMP-6) gene was hybridized to an ∼950 kbp I-CeuI-macrorestriction fragment from all 30 isolates and a probe specific for the bla(VIM-2) gene also hybridized to an ∼500 kbp I-CeuI-macrorestriction fragment from 1 isolate (BDC10). All 31 MBL-producing isolates shared an identical sequence type (ST), ST235, and they carried the same bla(OXA-50) allelic type, bla(OXA-50g). All MBL-producing isolates showed similar XbaI-macrorestriction patterns (similarity >85%), irrespective of MBL genotype. CONCLUSIONS P. aeruginosa ST235 carrying the chromosomally located bla(IMP-6) gene is widely disseminated in Korea.
In vitro activity of tedizolid (TR-700) against linezolid-resistant staphylococci.

OBJECTIVES To compare the activity of tedizolid (formally known as torezolid and TR-700) with that of 15 agents against a collection of linezolid-resistant staphylococci (164 coagulase-negative staphylococci and 5 Staphylococcus aureus). METHODS Antimicrobial susceptibility tests were performed using the broth microdilution method following the recommendations of the CLSI. RESULTS All isolates were susceptible to vancomycin and tigecycline. Based on the MIC(90) values, the potency of tedizolid against coagulase-negative staphylococci was >16-fold greater than that of linezolid. Tedizolid retained activity against most of the linezolid-resistant staphylococci tested, including multidrug-resistant isolates with elevated linezolid MICs (32 to >128 mg/L). Of the isolates, 79.2% and 31.4% were inhibited by tedizolid at ≤ 4 mg/L and ≤ 2 mg/L, respectively. CONCLUSIONS The results of this study confirm the activity of tedizolid against linezolid-resistant staphylococci. This new oxazolidinone could have an important role as a potential therapeutic agent against multidrug-resistant staphylococci.
Could liposomal amphotericin B (L-AMB) lock solutions be useful to inhibit Candida spp. biofilms on silicone biomaterials?

OBJECTIVES Candida infections associated with catheters remain difficult to manage. Antifungal lock strategies could be a therapeutic option when the device is difficult to remove or in combination with systemic treatment to increase efficacy. This study deals with the antibiofilm potential of liposomal amphotericin B (L-AMB) used as a lock solution to inhibit Candida albicans, Candida glabrata and Candida parapsilosis biofilms in vitro. METHODS Biofilms aged 12 h and 5 days were formed on silicone catheters. L-AMB (200 or 1000 mg/L) was added to biofilms and catheters were incubated for 4, 12 or 24 h at 37°C. L-AMB was then removed by washing. The metabolic activity of yeasts was assessed by the XTT method up to 48 h after the end of the locks to evaluate the persistence of the antibiofilm activity. Controls without antifungal were used as references to calculate the inhibition percentages induced by L-AMB lock solutions. RESULTS L-AMB (200 and 1000 mg/L) inhibited, for up to 48 h, C. albicans and C. glabrata biofilms by >70%, regardless of the lock duration. The activity of L-AMB (200 mg/L) against C. parapsilosis mature biofilms was lower and less sustained, especially for 4 h locks. CONCLUSIONS L-AMB (1000 mg/L) lock solutions strongly inhibited Candida spp. in young and mature biofilms for up to 48 h after the end of the lock. However, overall eradication of the biofilm was not obtained using 1000 mg/L L-AMB as a single lock. These results suggest the usefulness of systemic treatment combined with an L-AMB lock to control Candida spp. biofilms associated with catheters.
The study of occupational risk factors and interventions for baker's allergy and asthma among supermarket bakery workers

Background: Baker’s asthma is the most serious manifestation of occupational allergy among bakery workers. It is caused by IgE-mediated sensitisation and subsequent allergic reaction in the airways to specific occupational airborne allergens in flour or baking ingredients. Major aims of this study were to: characterise asthma phenotypes and environmental exposure to flour allergens among bakers and modifying factors; study associations between phenotype and environmental exposure and identify potential modifying factors of this association; determine the effectiveness of specific interventions in reducing exposure and the risk of sensitisation or allergic respiratory disease. Methods: A cross-sectional study was conducted among 517 bakery workers employed in 31 supermarkets. Health outcomes were assessed using a standardized questionnaire, immunological tests (sIgE, sIgG), methacholine challenge test and fractional exhaled nitric oxide (FeNO). Exposure assessment conducted preand post-intervention entailed determination of inhalable concentration of particulate mass and specific allergen levels. The intervention employed a group-randomised design to evaluate dust control measures. Results: Prevalence of probable occupational asthma (POA, 13%) was higher than atopic (AA, 6%), non-atopic (NAA, 6%) and work-aggravated asthma (WAA, 3%). Sensitisation to flour allergens was a major determinant of elevated FeNO among bakers. Bread bakers had the highest dust particulate (mean = 1.33 mg/m) and allergen exposures. Exposureresponse relationships followed a bell-shaped curve, with the prevalence of IgEsensitisation, allergic symptoms and POA, increasing up to 10-15 μg/m of airborne wheat allergen concentrations before declining. The association for IgE sensitization was not modified by IgG4 to wheat. The overall effect of the intervention revealed a 50% decrease in mean flour dust, wheat allergen and rye exposures in bakeries. Conclusion: Occupational asthma is the most common phenotype among supermarket bakery workers, with sensitisation to cereal flour allergens being the main determinant of allergic airway inflammation. The bell-shaped exposure response relationship is not modified by the presence of blocking antibodies and is probably due to a healthy worker effect. The multi-pronged intervention strategy was effective in reducing airborne flour dust and allergen levels. It is recommended that further studies investigate the long term health impact of these interventions in reducing the disease burden.
Characterization of a multidrug-resistant Acinetobacter baumannii strain carrying the blaNDM-1 and blaOXA-23 carbapenemase genes from the Czech Republic.

these studies. MRSA ST239 is found in significantly high numbers in Eastern Australia, and is associated with a broad spectrum of antimicrobial resistance and epidemic potential. The qacA/B genes are thought to be located on multiresistance plasmids, such as pSK1, and co-transmitted with plasmid-mediated antimicrobial resistance genes; hence their association with this multiresistant strain of MRSA is logical. The high prevalence of this ST239 strain could be due to selective pressure from the use of antiseptic products and/or the widespread use of antimicrobial agents. Our findings suggest the latter, given the absence of a corresponding rise in qacA/B genes with increased antiseptic hand solution use; however, the baseline use of antiseptic agents within the hospital could also explain the high prevalence of qacA/B genes even prior to the hand hygiene campaign. In either case, the high prevalence of qacA/B-carrying MRSA strains is concerning and carries potential implications for antimicrobial treatment, infection control and also MRSA decolonization regimes that are becoming increasingly popular. Clinical studies evaluating the impact of these resistance genes on hand hygiene treatments are currently lacking. However, a recent study showed that colonization with chlorhexidine-resistant strains of MRSA was associated with an increased risk of persistent MRSA carriage after decolonization therapy. In addition, chlorhexidine decolonization protocols have been shown to select for MRSA ST239 strains, all of which carried qacA/B genes. In regions where the prevalence of MRSA ST239 already exists at high levels, the potential for decolonization treatment failure with these agents exists and warrants further attention. In conclusion, a high prevalence of qacA/B genes was found in HA-MRSA isolates in this study. These genes correlated closely with the MRSA strain ST239. These findings highlight the need for further evaluation into the clinical implications of these genes in this era of increasing antiseptic use in hand hygiene and decolonization strategies.
Plasmid-encoded PER-7 β-lactamase responsible for ceftazidime resistance in Acinetobacter baumannii isolated in the United Arab Emirates.

OBJECTIVES To investigate the mechanism of ceftazidime resistance in two isogenic Acinetobacter baumannii strains from the United Arab Emirates. METHODS Two A. baumannii strains, NM55 and NM128, were isolated 4 months apart from a 6-year-old patient in the United Arab Emirates. Genotypic characterization was performed by PFGE and the MIC of ceftazidime was determined by the agar dilution method. Detection of bla(OXA) and metallo-β-lactamase genes was performed by multiplex PCR. Analysis of bla(PER-7), ISAba1, bla(ADC) and the ISCR1 element was carried out by standard PCR. Plasmid analysis was achieved by Southern blotting. RESULTS Strain NM55 was resistant to ceftazidime, whereas strain NM128 was susceptible. Both isolates carried the bla(OXA-23) and bla(OXA-64) genes and were identical according to their PFGE patterns. ISAba1 was present upstream of the bla(OXA-23) gene, but absent upstream of bla(ADC-26), in both strains. Strain NM55 possessed a bla(PER-7) gene with the presence of gst, a fragment of the abc transporter and a transposase gene downstream of it. The entire structure was part of an ISCR1 element and was located on an ≈ 200 kb plasmid in strain NM55, while the ceftazidime-susceptible NM128 strain carried an ≈ 180 kb plasmid without the bla(PER-7) gene. CONCLUSIONS Ceftazidime resistance was mediated by a PER-7 β-lactamase encoded in an ISCR1 element located on a plasmid. This represents the first detection of a PER-7 β-lactamase encoded by a plasmid in A. baumannii.