Medicated Scaffolds Prepared with Hydroxyapatite/Streptomycin Nanoparticles Encapsulated into Polylactide Microfibers.

The preparation, characterization, and controlled release of hydroxyapatite (HAp) nanoparticles loaded with streptomycin (STR) was studied. These nanoparticles are highly appropriate for the treatment of bacterial infections and are also promising for the treatment of cancer cells. The analyses involved scanning electron microscopy, dynamic light scattering (DLS) and Z-potential measurements, as well as infrared spectroscopy and X-ray diffraction. Both amorphous (ACP) and crystalline (cHAp) hydroxyapatite nanoparticles were considered since they differ in their release behavior (faster and slower for amorphous and crystalline particles, respectively). The encapsulated nanoparticles were finally incorporated into biodegradable and biocompatible polylactide (PLA) scaffolds. The STR load was carried out following different pathways during the synthesis/precipitation of the nanoparticles (i.e., nucleation steps) and also by simple adsorption once the nanoparticles were formed. The loaded nanoparticles were biocompatible according to the study of the cytotoxicity of extracts using different cell lines. FTIR microspectroscopy was also employed to evaluate the cytotoxic effect on cancer cell lines of nanoparticles internalized by endocytosis. The results were promising when amorphous nanoparticles were employed. The nanoparticles loaded with STR increased their size and changed their superficial negative charge to positive. The nanoparticles' crystallinity decreased, with the consequence that their crystal sizes reduced, when STR was incorporated into their structure. STR maintained its antibacterial activity, although it was reduced during the adsorption into the nanoparticles formed. The STR release was faster from the amorphous ACP nanoparticles and slower from the crystalline cHAp nanoparticles. However, in both cases, the STR release was slower when incorporated in calcium and phosphate during the synthesis. The biocompatibility of these nanoparticles was assayed by two approximations. When extracts from the nanoparticles were evaluated in cultures of cell lines, no cytotoxic damage was observed at concentrations of less than 10 mg/mL. This demonstrated their biocompatibility. Another experiment using FTIR microspectroscopy evaluated the cytotoxic effect of nanoparticles internalized by endocytosis in cancer cells. The results demonstrated slight damage to the biomacromolecules when the cells were treated with ACP nanoparticles. Both ACP and cHAp nanoparticles were efficiently encapsulated in PLA electrospun matrices, providing functionality and bioactive properties.

Rifampicin and clarithromycin (extended release) versus rifampicin and streptomycin for limited Buruli ulcer lesions: a randomised, open-label, non-inferiority phase 3 trial.

BACKGROUND: Buruli ulcer is a neglected tropical disease caused by Mycobacterium ulcerans infection that damages the skin and subcutis. It is most prevalent in western and central Africa and Australia. Standard antimicrobial treatment with oral rifampicin 10 mg/kg plus intramuscular streptomycin 15 mg/kg once daily for 8 weeks (RS8) is highly effective, but streptomycin injections are painful and potentially harmful. We aimed to compare the efficacy and tolerability of fully oral rifampicin 10 mg/kg plus clarithromycin 15 mg/kg extended release once daily for 8 weeks (RC8) with that of RS8 for treatment of early Buruli ulcer lesions. METHODS: We did an open-label, non-inferiority, randomised (1:1 with blocks of six), multicentre, phase 3 clinical trial comparing fully oral RC8 with RS8 in patients with early, limited Buruli ulcer lesions. There were four trial sites in hospitals in Ghana (Agogo, Tepa, Nkawie, Dunkwa) and one in Benin (Pobè). Participants were included if they were aged 5 years or older and had typical Buruli ulcer with no more than one lesion (caterories I and II) no larger than 10 cm in diameter. The trial was open label, and neither the investigators who took measurements of the lesions nor the attending doctors were masked to treatment assignment. The primary clinical endpoint was lesion healing (ie, full epithelialisation or stable scar) without recurrence at 52 weeks after start of antimicrobial therapy. The primary endpoint and safety were assessed in the intention-to-treat population. A sample size of 332 participants was calculated to detect inferiority of RC8 by a margin of 12%. This study was registered with ClinicalTrials.gov, NCT01659437. FINDINGS: Between Jan 1, 2013, and Dec 31, 2017, participants were recruited to the trial. We stopped recruitment after 310 participants. Median age of participants was 14 years (IQR 10-29) and 153 (52%) were female. 297 patients had PCR-confirmed Buruli ulcer; 151 (51%) were assigned to RS8 treatment, and 146 (49%) received oral RC8 treatment. In the RS8 group, lesions healed in 144 (95%, 95% CI 91 to 98) of 151 patients, whereas lesions healed in 140 (96%, 91 to 99) of 146 patients in the RC8 group. The difference in proportion, -0·5% (-5·2 to 4·2), was not significantly greater than zero (p=0·59), showing that RC8 treatment is non-inferior to RS8 treatment for lesion healing at 52 weeks. Treatment-related adverse events were recorded in 20 (13%) patients receiving RS8 and in nine (7%) patients receiving RC8. Most adverse events were grade 1-2, but one (1%) patient receiving RS8 developed serious ototoxicity and ended treatment after 6 weeks. No patients needed surgical resection. Four patients (two in each study group) had skin grafts. INTERPRETATION: Fully oral RC8 regimen was non-inferior to RS8 for treatment of early, limited Buruli ulcer and was associated with fewer adverse events. Therefore, we propose that fully oral RC8 should be the preferred therapy for early, limited lesions of Buruli ulcer. FUNDING: WHO with additional support from MAP International, American Leprosy Missions, Fondation Raoul Follereau France, Buruli ulcer Groningen Foundation, Sanofi-Pasteur, and BuruliVac.

Tuberculosis in the intensive care unit: alternative treatment regimens and association with mortality.

OBJECTIVES: Adequate anti-tuberculosis (TB) treatment is an important factor that can affect the patient's outcome. Higher mortality is found in patients who do not receive optimal treatment that includes isoniazid and rifampicin. The objective of this study is to evaluate the association of use of alternative TB treatment regimens (without rifampicin and isoniazid) and mortality among patients requiring intensive care. METHODS: Retrospective cohort study, from January 2010 to December 2018. Patients aged > 18 years with a TB diagnosis, admitted to the ICU of a general, tertiary care, university-affiliated hospital (Hospital de Clínicas de Porto Alegre - HCPA) were included. Data on TB treatment used and outcomes of treatment were collected. RESULTS: 462 patients met the inclusion criteria and were included in the analysis; 284 used the usual treatment regimen (rifampicin, isoniazid, pyrazinamide and ethambutol - all orally), and 178 used alternative treatment regimens (IV levofloxacin plus oral ethambutol plus IM streptomycin or IV amikacin, without rifampicin and isoniazid). The mortality was higher among users of alternative treatment regimens (63.5%) than among usual treatment regimen users (51.4%) (P = 0.011). In a multivariate analysis, age, albumin and death were independently associated with alternative treatment regimens use. CONCLUSIONS: TB programmes in which IV rifampicin is not widely available should consider including it, especially for critically ill TB patients, for whom there may be improved survival.

OBJECTIFS: Un traitement antituberculeux (TB) adéquat est un facteur important pouvant influencer les résultats du patient. Une mortalité plus élevée est observée chez les patients qui ne reçoivent pas un traitement optimal comprenant de l'isoniazide et de la rifampicine. L'objectif de cette étude est d'évaluer l'association entre l'utilisation d'autres schémas thérapeutiques anti-TB (sans rifampicine ni isoniazide) et la mortalité chez les patients nécessitant des soins intensifs. MÉTHODES: Etude de cohorte rétrospective, de janvier 2010 à décembre 2018. Les patients âgés de >18 ans avec un diagnostic de TB, admis à l'unité de soins intensifs d'un hôpital général, avec des soins tertiaires, affilié à l'Université (Hôpital de Clínicas de Porto Alegre-HCPA) ont été inclus. Des données sur le traitement anti-TB utilisé et les résultats du traitement ont été collectés. RÉSULTATS: 462 patients répondaient aux critères d'inclusion et ont été inclus dans l'analyse; 284 ont utilisé le schéma thérapeutique habituel (rifampicine, isoniazide, pyrazinamide et éthambutol - tous par voie orale) et 178 ont utilisé des schémas thérapeutiques alternatifs (lévofloxacine IV plus éthambutol oral plus streptomycine IM ou amikacine IV, sans rifampicine ni isoniazide). La mortalité était plus élevée chez les utilisateurs de schémas thérapeutiques alternatifs (63,5%) que chez les utilisateurs de schémas thérapeutiques habituels (51,4%) (P = 0,011). Dans l'analyse multivariée, l'âge, l'albumine et le décès ont été indépendamment associés à l'utilisation de schémas thérapeutiques alternatifs. CONCLUSIONS: Les programmes de lutte contre la TB dans lesquels la rifampicine IV n'est pas largement disponible devraient envisager de l'inclure, en particulier pour les patients atteints de TB et sévèrement malades, pour lesquels la survie peut être améliorée.

Transient Intestinal Colonization by a Live-Attenuated Oral Cholera Vaccine Induces Protective Immune Responses in Streptomycin-Treated Mice.

Current mouse models for evaluating the efficacy of live oral cholera vaccines (OCVs) have important limitations. Conventionally raised adult mice are resistant to intestinal colonization by Vibrio cholerae, but germfree mice can be colonized and have been used to study OCV immunogenicity. However, germfree animals have impaired immune systems and intestinal physiology; also, live OCVs colonize germfree mice for many months, which does not mimic the clearance kinetics of live OCVs in humans. In this study, we leveraged antibiotic-treated, conventionally raised adult mice to study the effects of transient intestinal colonization by a live OCV V. cholerae strain. In a single-dose vaccination regimen, we found that HaitiV, a live-attenuated OCV candidate, was cleared by streptomycin-treated adult mice within 2 weeks after oral inoculation. This transient colonization elicited far stronger adaptive immune correlates of protection against cholera than did inactivated whole-cell HaitiV. Infant mice from HaitiV-vaccinated dams were also significantly more protected from choleric disease than pups from inactivated-HaitiV-vaccinated dams. Our findings establish the benefits of antibiotic-treated mice for live-OCV studies as well as their limitations and underscore the immunogenicity of HaitiV.IMPORTANCE Oral cholera vaccines (OCVs) are being deployed to combat cholera, but current killed OCVs require multiple doses and show little efficacy in young children. Live OCVs have the potential to overcome these limitations, but small-animal models for testing OCVs have shortcomings. We used an antibiotic treatment protocol for conventional adult mice to study the effects of short-term colonization by a single dose of HaitiV, a live-OCV candidate. Vaccinated mice developed vibriocidal antibodies against V. cholerae and delivered pups that were resistant to cholera, whereas mice vaccinated with inactivated HaitiV did not. These findings demonstrate HaitiV's immunogenicity and suggest that this antibiotic treatment protocol will be useful for evaluating the efficacy of live OCVs.

Delivery of long-term-injectable agents for TB by lay carers: pragmatic randomised trial.

BACKGROUND: People with recurrent or drug-resistant TB require long courses of intramuscular injections. We evaluate a novel system in which patient-nominated lay carers were trained to deliver intramuscular injections to patients in their own homes. METHODS: A pragmatic, individually randomised non-inferiority trial was conducted at two hospitals in Malawi. Adults starting TB retreatment were recruited. Patients randomised to the intervention received home-based care from patient-nominated lay people trained to deliver intramuscular streptomycin. Patients receiving standard care were admitted to hospital for 2 months of streptomycin. The primary outcome was successful treatment (alive and on treatment) at the end of the intervention. RESULTS: Of 456 patients screened, 204 participants were randomised. The trial was terminated early due to futility. At the end of the intervention, 97/101 (96.0%) in the hospital arm were still alive and on treatment compared with 96/103 (93.2%) in the home-based arm (risk difference -0.03 (95% CI -0.09 to 0.03); p value 0.538). There were no differences in the proportion completing 8 months of anti-TB treatment; or the proportion experiencing 2-month sputum culture conversion. The mean cost of hospital-based management was US$1546.3 per person, compared to US$729.2 for home-based management. Home-based care reduced risk of catastrophic household costs by 84%. CONCLUSIONS: Although this trial failed to meet target recruitment, the available data demonstrate that training patient-nominated lay people has potential to provide a feasible solution to the operational challenges associated with delivering long-term-injectable drugs to people with recurrent or drug-resistant TB in resource-limited settings, and substantially reduce costs. Further data under operational conditions are required. TRIAL REGISTRATION NUMBER: ISRCTN05815615.

Chronotoxicity of Streptomycin-Induced Renal Injury in Mice.

The aim of the present study was to investigate the "chronotoxicity" of streptomycin (SM) in relation to its circadian periodicity. Male ICR mice were injected intraperitoneally with SM (780 mg/kg, one shot) one of six time points throughout the day. Mortality was monitored until 14 d after the injection and clearly differed depending on the timing of the injection (i.e., mice were more sensitive to injection during the dark phase). Moreover, when mice were administered with non-lethal doses of SM (550 mg/kg, every 24 h for 3 d, in the light phase or dark phase), the levels of nephrotoxicity indicators (blood urea nitrogen and renal levels of malondialdehyde and cyclooxygenase-2) were significantly increased by the injection in the dark phase, but not in the light phase. These results suggested that SM showed clear chronotoxicity. Our current data indicated that chronotoxicology may provide valuable information on the importance of injection timings for evaluations of toxicity and undesirable side effects.

Role of local streptomycin in prevention of surgical site infection in TB spine.

PURPOSE: Surgical site infection (SSI) continues to be one of the most common post-operative complications in most spine surgeries. Patients with tuberculosis (TB) of spine are more at risk of developing this complication due to a number of reasons. This adds to significant morbidity and economic burden on patients adversely affecting the mental status and quality of life of patients. The aim of this study was to investigate the role of local streptomycin in preventing SSI in patients undergoing surgical management of spinal TB. METHODS: In total, 56 patients who underwent surgical management for radiologically proven TB spine divided into two groups were included in the study. Group A included 30 patients with no local streptomycin administered intraoperatively, while group B included 26 patients operated in the later part of study with the use of local streptomycin intraoperatively. The two groups were compared and the outcome criteria analysed were SSI rate, length of hospital stay, duration of post-operative antibiotics and need for debridement. RESULTS: Length of hospital stay (group A: 18.4 ± 6.9 days; group B: 9.7 ± 3.9 days) and duration of post-operative antibiotics (group A: 8.1 ± 1.6 days; group B: 6.2 ± 2.1 days) were significantly higher in group A when compared with group B. SSI rate (group A: 13.34%; group B: 3.84%) and need for debridement (group A: 10%; group B: 3.84%) were higher in group A, but the difference was not statistically significant. CONCLUSION: Intraoperative administration of local streptomycin significantly reduces the length of hospital stay and duration of antibiotic administration in post-operative period in patients undergoing surgery for TB spine.

High-Dose Rifamycins Enable Shorter Oral Treatment in a Murine Model of Mycobacterium ulcerans Disease.

Buruli ulcer (BU), caused by Mycobacterium ulcerans, is a neglected tropical skin and soft tissue infection that is associated with disability and social stigma. The mainstay of BU treatment is an 8-week course of rifampin (RIF) at 10 mg/kg of body weight and 150 mg/kg streptomycin (STR). Recently, the injectable STR has been shown to be replaceable with oral clarithromycin (CLR) for smaller lesions for the last 4 weeks of treatment. A shorter, all-oral, highly efficient regimen for BU is needed, as the long treatment duration and indirect costs currently burden patients and health systems. Increasing the dose of RIF or replacing it with the more potent rifamycin drug rifapentine (RPT) could provide such a regimen. Here, we performed a dose-ranging experiment of RIF and RPT in combination with CLR over 4 weeks of treatment in a mouse model of M. ulcerans disease. A clear dose-dependent effect of RIF on both clinical and microbiological outcomes was found, with no ceiling effect observed with tested doses up to 40 mg/kg. RPT-containing regimens were more effective on M. ulcerans All RPT-containing regimens achieved culture negativity after only 4 weeks, while only the regimen with the highest RIF dose (40 mg/kg) did so. We conclude that there is dose-dependent efficacy of both RIF and RPT and that a ceiling effect is not reached with the current standard regimen used in the clinic. A regimen based on higher rifamycin doses than are currently being evaluated against tuberculosis in clinical trials could shorten and improve therapy of Buruli ulcer.

Pollen reverses decreased lifespan, altered nutritional metabolism and suppressed immunity in honey bees (Apis mellifera) treated with antibiotics.

Nutrition is involved in regulating multiple aspects of honey bee biology such as caste, immunity, lifespan, growth and behavioral development. Deformed wing virus (DWV) is a major pathogenic factor which threatens honey bee populations, and its replication is regulated by the nutrition status and immune response of honey bees. The alimentary canal of the honey bee is home to a diverse microbial community that provides essential nutrients and serves to bolster immune responses. However, to what extent gut bacteria affect honey bee nutrition metabolism and immunity with respect to DWV has not been investigated fully. In this study, newly emerged worker bees were subjected to four diets that contained (1) pollen, (2) pollen and antibiotics, (3) neither pollen nor antibiotics or (4) antibiotics alone. The expression level of two nutrition genes target of rapamycin (tor) and insulin like peptide (ilp1), one nutritional marker gene vitellogenin (vg), five major royal jellyprotein genes (mrjp1-5), one antimicrobial peptide regulating gene relish (rel), and DWV virus titer and its replication intermediate, negative RNA strand, were determined by qRT-PCR from the honey bees at 7 days post-antibiotic treatment. Additionally, honey bee head mass and survival rate were measured. We observed that antibiotics decreased the expression of tor and rel, and increased DWV titer and its replication activity. Expression of ilp1, mrjp1-5 and vg, and honey bee head mass were also reduced compared with bees on a pollen diet. Antibiotics also caused a significant drop in survivorship, which could be rescued by addition of pollen to the diet. Of importance, pollen could partially rescue the loss of vg and mrjp2 while also increasing the head mass of antibiotic-treated bees. Our results illuminate the roles of bacteria in honey bee nutrition, metabolism and immunity, which confer the ability to inhibit virus replication, extend honey bee lifespan and improve overall health.

Perianal Tuberculosis: Lessons Learned in 57 Patients From 743 Samples of Histopathology and Polymerase Chain Reaction and a Systematic Review of Literature.

BACKGROUND: Few data are published on perianal tuberculosis. OBJECTIVE: This study aimed to determine the best method to diagnose tuberculosis in patients with fistula-in-ano and to conduct a systematic review to determine the incidence and characteristics of tuberculosis fistula-in-ano. DATA SOURCES: The prospective study data and existing literature were derived from PubMed, Google scholar, and Scopus STUDY SELECTION:: Prospective analysis of patients with tuberculous fistula-in-ano treated between 2014 and 2018 was conducted, and a systematic review of studies describing ≥3 patients with tuberculosis fistula-in-ano was completed. INTERVENTION: Testing of tuberculosis was performed by histopathology or polymerase chain reaction of tissue or pus from the fistula tract. MAIN OUTCOME MEASURES: The primary outcomes measured were the detection rate of various tests to detect tuberculosis in fistula-in-ano and the prevalence rate of tuberculosis in simple versus complex fistulas. RESULTS: In 637 samples (410 patients) tested, tuberculosis was detected in 49 samples (43 patients). Additional samples (n = 106) sent in patients with a high index of suspicion tested positive in 14 more patients. Thus, overall, 63 samples tested positive in 57 patients (total: 743 samples in 410 patients were tested). Tuberculosis was detected in 2 of 181 patients (1.1%) in tissue (histopathology), in 28 of 341 patients (8.2%) in tissue (polymerase chain reaction), and in 19 of 115 patients (16.5%) in pus (polymerase chain reaction) samples. To detect tuberculosis, tissue (polymerase chain reaction) was significantly better than tissue (histopathology) (28/341 vs 2/181, p < 0.00001) and pus (polymerase chain reaction) was significantly better than tissue (polymerase chain reaction) (19/115 vs 28/341, p < 0.0009). Tuberculosis was significantly more common in complex fistulas than in simple fistulas (20.3% vs 7.2%, p = 0.0002). The systematic review (n = 199) highlighted that tubercular fistulas are more common in recurrent and complex fistulas and in tuberculosis endemic regions. LIMITATIONS: The true sensitivity and specificity of each testing modality could not be determined because not all patients with tuberculosis fistula-in-ano were tested by every diagnostic modality studied. CONCLUSIONS: The tuberculosis detection rate of polymerase chain reaction was significantly higher than histopathology. Among polymerase chain reaction, pus had higher detection rate than tissue. Tuberculosis was associated with more complex and recurrent fistulas.

The influence of antibiotics on gut bacteria diversity associated with laboratory-reared Bactrocera dorsalis.

The oriental fruit fly Bactrocera dorsalis (Hendel) is a destructive insect pest of a wide range of fruit crops. Commensal bacteria play a very important part in the development, reproduction, and fitness of their host fruit fly. Uncovering the function of gut bacteria has become a worldwide quest. Using antibiotics to remove gut bacteria is a common method to investigate gut bacteria function. In the present study, three types of antibiotics (tetracycline, ampicillin, and streptomycin), each with four different concentrations, were used to test their effect on the gut bacteria diversity of laboratory-reared B. dorsalis. Combined antibiotics can change bacteria diversity, including cultivable and uncultivable bacteria, for both male and female adult flies. Secondary bacteria became the dominant population in female and male adult flies with the decrease in normally predominant bacteria. However, in larvae, only the predominant bacteria decreased, the bacteria diversity did not change a lot, likely because of the short acting time of the antibiotics. The bacteria diversity did not differ among fruit fly treatments with antibiotics of different concentrations. This study showed the dynamic changes of gut bacterial diversity in antibiotics-treated flies, and provides a foundation for research on the function of gut bacteria of the oriental fruit fly.

Continuous hypoxia reduces the concentration of streptomycin in the blood.

BACKGROUND: A high incidence and mortality of plague in the past two decades occurred in the Qinghai-Tibet Plateau, China. High dose streptomycin (6-8 g/d) remained the first practical strategy for controlling the progressive, vicious clinical circumstances for patients with pneumonic plague in the Plateau, as opposed to the routine dosage recommended by the World Health Organization. To investigate whether patients with pneumonic plague truly required a large dosage of streptomycin in the hypoxic environment of the Tibetan Plateau, we investigated the hypothesis that hypoxic environment would change the pharmacokinetics of streptomycin in vivo. METHODS: (1) We retrospectively analyzed the data of pneumonic plague patients administered streptomycin from January 1, 2000 to December 31, 2012 in these areas, which came from the database of the Qinghai Center for Disease Control; and (2) We used a persistent hypoxia chamber to simulate the plateau hypoxic environment and fed Sprague Dawley rats in the chambers for one month. Then, we continuously administered hypoxic rats a single loading dose (200 mg/kg) of streptomycin and analyzed its concentrations by high performance liquid chromatography. The pharmacokinetic profiles were analyzed using a non-compartmental method in the Phoenix WinNonlin program. RESULTS: (1) There were 32 cases of patients with pneumonic plague in the past two decades totally and 9 of them died (all-cause mortality 28.125%, 9/32), including 7 cases died of delayed diagnosis without treatment of streptomycin, and the only 2 patients received normal dose of streptomycin. (2) The pharmacokinetic behaviors of streptomycin were different between the hypoxic and normal rats. Administration in a hypoxic state resulted in 74.81% and 29.28% decreases in maximum plasma concentration and area under the concentration-time curve from time zero to infinity compared with those values under normal condition for streptomycin. CONCLUSIONS: These results indicated that hypoxic condition could significantly decrease the absorption rate and extent of streptomycin. Therefore, patients with pneumonic plague require higher doses of streptomycin to maintain effective drug concentrations in Qing Hai and the Tibetan Plateau.

Control of Citrus Huanglongbing via Trunk Injection of Plant Defense Activators and Antibiotics.

Citrus huanglongbing (HLB) or greening is a devastating disease of citrus worldwide and no effective control measure is currently available. Plant defense activators environmentally friendly compounds capable of inducing resistance against many plant pathogens. Earlier studies showed that foliar spray of plant defense inducers could slow down HLB disease progress. In this study, eight plant defense activators and three antibiotics were evaluated in three field trials for their effect to control HLB by trunk injection of young and mature sweet orange trees. Results showed that four trunk injections of several activators, including salicylic acid, oxalic acid, acibenzolar-S-methyl, and potassium phosphate, provided significant control of HLB by suppressing 'Candidatus Liberibacter asiaticus' titer and disease progress. Trunk injection of penicillin, streptomycin, and oxytetracycline hydrochloride resulted in excellent control of HLB. In general, antibiotics were more effective in reduction of 'Ca. L. asiaticus' titer and HLB symptom expressions than plant defense activators. These treatments also resulted in increased yield and better fruit quality. Injection of both salicylic acid and acibenzolar-S-methyl led to significant induction of pathogenesis-related (PR) genes PR-1 and PR-2 genes. Meanwhile, injection of either potassium phosphate or oxalic acid resulted in significant induction of PR-2 or PR-15 gene expression, respectively. These results suggested that HLB diseased trees remained inducible for systemic acquired resistance under field conditions. In summary, this study presents information regarding controlling HLB via trunk injection of plant defense activators and antibiotics, which helps citrus growers in decision making regarding developing an effective HLB management program.

Cytopenia in adult brucellosis patients.

BACKGROUND & OBJECTIVES: Brucellosis can lead to haematological abnormalities including cytopenia confusing with haematological malignancies. The aim of this study was to compare the main characteristics of brucellosis patients without cytopenia (Group 1) and with cytopenia (Group 2). METHODS: This five-year period study which was performed in two referral hospitals in Turkey, included all adult brucellosis patients. Abnormally, low counts of leucocyte or haemoglobin or platelets in a patient were considered as cytopenia. The demographics, clinical, laboratory, treatment and outcome data were analyzed. RESULTS: A total of 484 brucellosis patients were enrolled. Among the cases, 162 (33.5%) of them had cytopenia. One hundred and four (21.5%) had anaemia, 88 (18.8%) had thrombocytopenia, 71 (14.6%) had leucopenia and 28 (5.8%) had pancytopenia. The mean age of group 2 was 35.01±16.05 yr and it was 33.31±14.39 yr in group 1. While there was no difference between the groups in terms of duration of treatment, the median length of hospital stay (LOS) was significantly longer in group 2 (9 vs 10 days; P<0.001). The most frequently applied combination therapy consisted of doxycycline plus rifampicin and doxycycline plus streptomycin regimens. No significant difference was observed in terms of duration of treatment, LOS and restoration time of cytopenia between the patients who received either of these combinations. INTERPRETATION & CONCLUSIONS: Our findings suggested that the patients with cytopenia should be investigated for brucellosis, especially if living in, or with a history of travel to, endemic areas, in view of the increase in world travel.

Mixed pneumonic plague and nosocomial MDR-bacterial infection of lung: a rare case report.

BACKGROUND: Plague is a life-threatening disease caused by the bacterium, Yersinia pestis. Madagascar is the leading country for human plague cases worldwide. Human plague is a serious disease, particularly in its septicaemic and pneumonic forms. We report a case of pneumonic plague co-infected by a MDR-Stenotrophomonas maltophilia. CASE PRESENTATION: A 24 year-old man originated from Soavinandriana, a plague focus, felt uneasy and developed high fever with chills. He started treatment by himself, by private medical care and by a traditional healer for nine days moving several times from place to place. His condition had deteriorated when he presented to a district hospital with a syndrome of dyspnea, bronchial rale and altered state of consciousness. Two days later, plague diagnosis, performed as a last resort, revealed a positive F1 antigen on rapid diagnostic test. Additional tests (pla PCR and plague serology) evidenced a Y. pestis infection. However, streptomycin treatment did not achieve a complete recovery as the course of disease was complicated by the presence of MDR-S. maltophilia in his lung. This opportunistic infection could have been favored by an immunosuppression due to Y. pestis pulmonary infection and probably been acquired during his stay at a District Hospital. He was treated with a combination of ciprofloxacin and gentamycin and recovered fully. CONCLUSIONS: Pneumonic plague infection may promote another virulent or avirulent bacterial infection particularly when it is not initially suspected. However, coinfection is rarely described and its occurrence frequency is unknown. In middle or low resources areas, which is the case of most plague endemic countries, control and prevention of infections in health facilities is not optimal. Co-infection with an opportunistic pathogen agent, such as S. maltophilia, is a risk which must not be disregarded as demonstrated by this case report. When deciding of a national control strategy, it should be taken into account in the choice of the first line treatment.

Localized Injection of Streptomycin, Kenacort and Lidocaine combination for Symptomatic Pain Management of Knee Osteoarthritis.

OBJECTIVE: To determine the frequency of reduction of pain in symptomatic knee osteoarthritis by using combination injections. METHODS: The experimental study was conducted from January 1, 2010, to December 31, 2016,at Al-Noor Surgery Hospital, Chakwal, Pakistan, and comprised patients suffering from symptomatic knee osteoarthritis. All patients were injected intra-articularly and peri-articularily with a combination of streptomycin, kenacort and lidocaine. The effects of this injection were recorded immediately after injection, after a month and after a year. Data was analyzed using SPSS 21. RESULTS: Of the 169 patients, there were 70(41.40%) males and 99(58.60%) females. The overall mean age and pain duration was 59.27±7.79 years and10.5±5.1 years respectively. No patient had pain immediately after the injection and after a month of follow-up. After a year, 145(86%) had a complete loss of pain compared to the baseline. Three (1.77%) patients required repetition of injection after a year. None of the patients suffered from septic arthritis or localised flare-ups and no one opted for knee joint arthoplasty. CONCLUSIONS: Combination of streptomycin, low-dose corticosteroids and lidocaine hadimmediate and prolonged effect in reducing pain in patients with knee osteoarthritis.

Antibiotics Suppress Activation of Intestinal Mucosal Mast Cells and Reduce Dietary Lipid Absorption in Sprague-Dawley Rats.

BACKGROUND & AIMS: The gut microbiota affects intestinal permeability and mucosal mast cells (MMCs) responses. Activation of MMCs has been associated with absorption of dietary fat. We investigated whether the gut microbiota contributes to the fat-induced activation of MMCs in rats, and how antibiotics might affect this process. METHODS: Adult male Sprague-Dawley rats were given streptomycin and penicillin for 4 days (n = 6-8) to reduce the abundance of their gut flora, or normal drinking water (controls, n = 6-8). They underwent lymph fistula surgery and after an overnight recovery were given an intraduodenal bolus of intralipid. We collected intestinal tissues and lymph fluid and assessed activation of MMCs, intestinal permeability, and fat transport parameters. RESULTS: Compared with controls, intestinal lymph from rats given antibiotics had reduced levels of mucosal mast cell protease II (produced by MMCs) and decreased activity of diamine oxidase (produced by enterocytes) (P < .05). Rats given antibiotics had reduced intestinal permeability in response to dietary lipid compared with controls (P < .01). Unexpectedly, antibiotics also reduced lymphatic transport of triacylglycerol and phospholipid (P < .01), concomitant with decreased levels of mucosal apolipoproteins B, A-I, and A-IV (P < .01). No differences were found in intestinal motility or luminal pancreatic lipase activity between rats given antibiotics and controls. These effects were not seen with an acute dose of antibiotics or 4 weeks after the antibiotic regimen ended. CONCLUSIONS: The intestinal microbiota appears to activate MMCs after the ingestion of fat in rats; this contributes to fat-induced intestinal permeability. We found that the gut microbiome promotes absorption of lipid, probably by intestinal production of apolipoproteins and secretion of chylomicrons.

In vitro activity of alpha-viniferin isolated from the roots of Carex humilis against Mycobacterium tuberculosis.

This study explores the antitubercular activity of α-viniferin, a bioactive phytochemical compound obtained from Carex humilis. α-Viniferin was active against both drug-susceptible and -resistant strains of Mycobacterium tuberculosis at MIC50s of 4.6 µM in culture broth medium and MIC50s of 2.3-4.6 µM inside macrophages and pneumocytes. In combination with streptomycin and ethambutol, α-viniferin exhibited an additive effect and partial synergy, respectively, against M. tuberculosis H37Rv. α-Viniferin also did not show cytotoxicity in any of the cell lines tested up to a concentration of 147 µM, which gives this compound a selectivity index of >32. Moreover, α-viniferin was active against 3 Staphylococcus species, including methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and methicillin-resistant Staphylococcus epidermidis (MRSE).

Clinical outcomes of Ghanaian Buruli ulcer patients who defaulted from antimicrobial therapy.

OBJECTIVES: Buruli ulcer (BU) is a tropical skin disease caused by infection with Mycobacterium ulcerans, which is currently treated with 8 weeks of streptomycin and rifampicin. The evidence to treat BU for a duration of 8 weeks is limited; a recent retrospective study from Australia suggested that a shorter course of antimicrobial therapy might be equally effective. We studied the outcomes of BU in a cohort of Ghanaian patients who defaulted from treatment and as such received less than 8 weeks of antimicrobial therapy. METHODS: A number of days of antimicrobial therapy and patient and lesion characteristics were recorded from charts from a cohort of BU patients treated at Nkawie-Toase hospital between 2008 and 2012. Patients who defaulted from treatment were retrieved, and lesion characteristics and functional limitations were recorded. RESULTS: About 54% of patients defaulted from therapy or wound care. Forty-seven defaulters with follow-up completed had received <56 days of antibiotics. 84% of these patients healed after 32 days or less of antibiotics. There appeared to be an increased rate of healing in smaller lesions; 94% of WHO category I lesions had healed after 32 days or less of antibiotics. CONCLUSION: Although numbers were small, and a potential for bias exists, our findings suggest that a reduction in the duration of antimicrobial therapy in BU in small, early lesions is feasible. These findings can serve as a basis for future well-designed studies.