Rationale:Salmonella(S.)typhi is a rare cause of osteomyelitis in immunocompetent adults.Extensive drug resistance(XDR)may lead to more complicated cases of S.typhi osteomyelitis.Patient concern:A 55-year-old female p...Rationale:Salmonella(S.)typhi is a rare cause of osteomyelitis in immunocompetent adults.Extensive drug resistance(XDR)may lead to more complicated cases of S.typhi osteomyelitis.Patient concern:A 55-year-old female presented with a persistent low-grade fever and a swelling on her lower left chest with a sinus discharging purulent fluid for the past 8 months.Her symptoms had been unresponsive to previous anti-microbial therapy.Diagnosis:Rib osteomyelitis caused by XDR S.typhi.Interventions:Surgical wound debridement,left 7th-9th rib resection and intravenous Ⅳ meropenem were done.Outcome:Fever resolved and left-sided swelling resected without recurrence.Lessons:The prevalence of XDR S.typhi is growing in South Asia and should be considered as the differential diagnosis of chronic osteomyelitis.展开更多
Emerging and rapidly spreading multidrug resistant bacteria constitute a rising public health concern worldwide. Acinetobacter baumannii is one of these bacteria that cause different infections including pneumonia, ba...Emerging and rapidly spreading multidrug resistant bacteria constitute a rising public health concern worldwide. Acinetobacter baumannii is one of these bacteria that cause different infections including pneumonia, bacteremia, meningitis, soft-tissue, and urinary tract infections, and are associated with high mortality and economic burden. We present a case of a 43-year-old woman, admitted at the department of orthopedics, regional hospital of Ourossogui, North-East of Senegal for soft-tissue injuries. Initially diagnosed with Yersinia pestis infection, the patient was well managed before being released. Supplementary sampling for confirmatory tests allowed the detection of an extensively drug-resistant Acinetobacter baumannii clone.展开更多
Background: The emergence of carbapenemase producing Acinetobacter baumannii is increasingly reported nowadays and constitutes a major problem to the intensive care unit (ICU) patients with notable extensive-drug resi...Background: The emergence of carbapenemase producing Acinetobacter baumannii is increasingly reported nowadays and constitutes a major problem to the intensive care unit (ICU) patients with notable extensive-drug resistance ability. The study investigates carbapenemase producing A. baumannii strains exhibiting an extensively drug-resistant (XDR) phenotype, isolated from ICU patients in Khartoum. Methods: A total of 100 nonduplicate Gram-negative coccobacilli strains were obtained from microbiology laboratory of ICU patients’ clinical isolates. Molecular identification of A. baumannii was performed by targeting 16S rRNA gene using specifically designed primers. Then, XDR strains were determined by susceptibility testing (disc diffusion). For detection of carbapenemase genes Polymerase chain reaction (PCR) was carried out. Result: Of 100 ICU clinical isolates, 38 (38.0%) was confirmed A. baumannii strains, those strains showed 100% carbapenem resistance and 60.5% extensive drug resistance to the antibiotics tested. The frequency of carbapenemase producer was 57.9% (22/38) of carbapenem resistance A. baumannii (CRAB). The most common carbapenemase associated with resistance was blaOXA gene followed by blaNDM and blaGES A. baumannii isolates. The co-occurrence of blaOXA-48-like and blaNDM, blaOXA-23-like and blaOXA-51, and blaNDM-1 and blaOXA-51 was detected in 22.7%, 18.2% strains and 4.5% respectively. A unique characteristic of our findings was the coharbouring of the genes blaNDM-1, blaOXA-23-like, blaOXA-51 and blaOXA-143 in 9.1% strains (2/22), and this was the first report in the Khartoum city, Sudan. Conclusion: We have demonstrated for the first time a high prevalence of XDR-carbapenemase producing A. baumannii clinical isolates from ICU patients in Khartoum. Also an emergent blaOXA-143 was reported as High-Risk Clones. This highlights the routine mentoring of XDR-carbapenemase producing A. baumannii to avoid clone dissemination in our region hospitals.展开更多
Tuberculosis (TB), caused by Mycobacterium tuberculosis is an infectious deadly disease and the treatment of which is one of the most severe challenges at the global level. Currently more than 20 chemical medications ...Tuberculosis (TB), caused by Mycobacterium tuberculosis is an infectious deadly disease and the treatment of which is one of the most severe challenges at the global level. Currently more than 20 chemical medications are described for the treatment of TB. Regardless of availability of several drugs to treat TB, the causative agent, M. tuberculosis is nowadays getting resistant toward the conventional drugs and leading to conditions known as Multidrug-resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB). This situation has terrified the global health community and raised a demand for new anti-tuberculosis drugs. Medicinal plants have been used to cure different common as well as lethal diseases by ancient civilizations due to its virtue of variety of chemical compounds which may have some important remedial properties. The aim of the present review is to focus the anti-tubercular medicinal plants native to India as well as the plants effective against MDR or XDR-TB across the globe. In the present review, we have addressed 25 medicinal plants for TB and 16 plants effective against MDR-TB testified from India and 23 herbal plants described for MDR-TB across the world during 2011-2015. These herbal plants can serve as promising candidates for developing novel medications to combat multidrug resistant M. tuberculosis.展开更多
India tops the global list for Drug resistant Tuberculosis, but inadequate and expensive laboratory culture techniques have led to delay in the diagnosis and treatment. We studied the potential of an alternative metho...India tops the global list for Drug resistant Tuberculosis, but inadequate and expensive laboratory culture techniques have led to delay in the diagnosis and treatment. We studied the potential of an alternative method which could be cost-effective by combining the drugs in the same tube for identification of drug resistance. Drug Susceptibility Test (DST) results of 1000 sputum samples are got from suspected TB patients against INH (isoniazid) and Rifampicin by two techniques: a) a modified technique with both drugs in the same MGIT tube and b) a standard technique with the antibiotics in separate MGIT tubes for the diagnosis of MDR-TB (Multidrug Resistant). 39 samples were contaminated and were excluded from final analysis. 198 were smear positives by the concentrated Ziehl-Neelsen’s staining method. 219 were found to be culture positive out of which 195 were identified as M. tuberculosis complex. 40 (20.5%) strains were identified as MDR-TB by the conventional method and 39 were picked up by the modified DST. INH and Rifampicin mono-resistance accounted for 32 (16.4%) and 4 (2%) respectively. 99% concordance was observed between the two tests in categorizing MDR-TB. Similarly modified technique with combination of the second line Antibiotics-Ofloxacin, Kanamycin and Capreomycin was applied on the identified MDR strains in a stepwise manner. 6 (15%) were identified as Pre-XDR strains and 2 (5%) were found to be XDR-TB strains. This study implies that combining drugs in the same tube may be an equivalent and possibly a cost-effective alternative which needs to be explored further.展开更多
Several related substances were detected at trace level in (2R)-2,3-dihydro-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl] phenoxy] methyl]imidazo[2, 1-b]oxazole drug substance by a newly devel...Several related substances were detected at trace level in (2R)-2,3-dihydro-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl] phenoxy] methyl]imidazo[2, 1-b]oxazole drug substance by a newly developed high-performance liquid chromatography method. All related substances were characterized rapidly but some impurities were found to be intermediates. Proposed structures were further confirmed by characterization using NMR, FT-IR, and HRMS techniques. Based on the spectroscopic data;unknown related sub-stances were characterized as 1-(Methylsulfonyl)-4-[4-(trifluoromethoxy) phenoxy]piperidine;4-{4-[4-(Tri-fluoromethoxy)-phenoxy]piperidin-1-yl}phenol and 4-{4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl}phenyl methane sulfonate;4-Bromophenyl methane sulfonate, Ethyl 3,6-dihydro-1(2H)-pyridine carboxylate, (2S)-3-(4-Bromophenoxy)-2-hydroxy-2-methylpropyl methane sulfonate, (2S)-3-(4-Bromophenoxy)-2-methylpropane-1,2-diyldimethane-sulfonate, (2S)-2-Methyl-3-(4-{4-[4-(trifluoromethoxy) phenoxy]-piperidin-1-yl} phenoxy)-propane-1,2-diyldimethane sulfonate, (S)-3-(4-Bromophenoxy)-2-methyl-propane-1,2-diol and corresponding Enantiomer, (2R)-2-[(4-Bromo-phenoxy)methyl]-2-methyloxirane and (2R)-2-[(4-bromophenoxy)methyl]-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole. A possible mechanism for the formation of these related substances is also proposed.展开更多
Objectives: Bedaquiline (BDQ) is the first new anti-tuberculosis (TB) drug introduced to the market after 45 years. Recent studies have shown the potential benefits of adding bedaquiline to regimens for drug-resistant...Objectives: Bedaquiline (BDQ) is the first new anti-tuberculosis (TB) drug introduced to the market after 45 years. Recent studies have shown the potential benefits of adding bedaquiline to regimens for drug-resistant TB (DR-TB). In search of more effective regimens for DR-TB, bedaquiline was introduced in the TB program in the Philippines under operational research to assess its effectiveness, safety, and tolerability when given with background regimens among patients with multi-or extensively DR-TB (MDR/XDR-TB). Design: A prospective cohort study of patients with MDR/XDR-TB was given with a bedaquiline-containing regimen from June 2016 to May 2017. Demographic data, presence of comorbidities, and microbiologic profile on entry were recorded. Bedaquiline was administered at the recommended dose of 400 mg once daily for 14 days, then 200 mg three times a week for 22 weeks together with World Health Organization (WHO)-compliant background regimen. The time to culture conversion, interim outcomes at the 6th month of treatment, end-of-treatment outcomes, and post-treatment follow-up outcomes after one year was determined. The frequency and severity of adverse events (SAE) were recorded as part of pharmacovigilance. Results: Seventy-five patients were given with bedaquiline-containing regimen during the study period. Forty-two (56.0%) had second-line injectable resistance, 23 (30.7%) had fluoroquinolone-resistance, 6 (8.0%) had MDR-TB, and 4 (5.3%) had XDR-TB. In the 6th month of post-enrolment, 79% were culture-negative. The treatment success rate was 65.3% (37 were cured and 12 completed treatment), 7 (9.3%) died, 17 (22.7%) lost to follow-up, and 2 (2.7%) were withdrawn from treatment. Adverse events included vomiting (80%), dizziness (69%), nausea (52%), cough (44%), and headache (36%). The post-treatment follow-up of 49 patients in the 12th month showed 92% were culture-negative while 8% of TBC were not done. Conclusion: Bedaquiline-containing regimens for patients with MDR/XDR-TB were highly effective with an acceptable safety profile and favorable treatment outcomes, but the proportion of patients who lost to follow-up remains substantial.展开更多
Rifampicin-resistant tuberculosis (RR-TB) is a global public health problem caused by mycobacterium tuberculosis resistant to Rifampicin. Drug-induced peripheral neuropathy and neurotoxicity are well-known adverse eff...Rifampicin-resistant tuberculosis (RR-TB) is a global public health problem caused by mycobacterium tuberculosis resistant to Rifampicin. Drug-induced peripheral neuropathy and neurotoxicity are well-known adverse effects of treatment regimens that cause significant morbidity. Pyridoxine is often added to treatment regimens for the prevention and/or treatment of these side effects. The basis and effectiveness of this practice are unclear. We conducted a systematic review to evaluate the effectiveness of pyridoxine in preventing and/or treating neuropathy and neurotoxicity associated with RR-TB treatment. We included studies with patients with RR-TB who experienced neuropathy or neurotoxicity attributed to RR-TB regimens and were given pyridoxine. Our findings showed contradicting evidence on the use of pyridoxine for preventing or treating neurotoxicity due to cycloserine in the treatment of RR-TB. Moreover, pyridoxine did not have a protective effect against neuropathy and/or neurotoxicity caused by other RR-TB regimens that do not contain isoniazid. In conclusion, we found that withdrawing or withholding medications such as linezolid, cycloserine, thioamides, fluoroquinolones, and ethambutol, implicated in causing neuropathy or neurotoxicity was more effective than using pyridoxine to stop the progression of symptoms, and in some instances, led to their reversal over time.展开更多
文摘Rationale:Salmonella(S.)typhi is a rare cause of osteomyelitis in immunocompetent adults.Extensive drug resistance(XDR)may lead to more complicated cases of S.typhi osteomyelitis.Patient concern:A 55-year-old female presented with a persistent low-grade fever and a swelling on her lower left chest with a sinus discharging purulent fluid for the past 8 months.Her symptoms had been unresponsive to previous anti-microbial therapy.Diagnosis:Rib osteomyelitis caused by XDR S.typhi.Interventions:Surgical wound debridement,left 7th-9th rib resection and intravenous Ⅳ meropenem were done.Outcome:Fever resolved and left-sided swelling resected without recurrence.Lessons:The prevalence of XDR S.typhi is growing in South Asia and should be considered as the differential diagnosis of chronic osteomyelitis.
文摘Emerging and rapidly spreading multidrug resistant bacteria constitute a rising public health concern worldwide. Acinetobacter baumannii is one of these bacteria that cause different infections including pneumonia, bacteremia, meningitis, soft-tissue, and urinary tract infections, and are associated with high mortality and economic burden. We present a case of a 43-year-old woman, admitted at the department of orthopedics, regional hospital of Ourossogui, North-East of Senegal for soft-tissue injuries. Initially diagnosed with Yersinia pestis infection, the patient was well managed before being released. Supplementary sampling for confirmatory tests allowed the detection of an extensively drug-resistant Acinetobacter baumannii clone.
文摘Background: The emergence of carbapenemase producing Acinetobacter baumannii is increasingly reported nowadays and constitutes a major problem to the intensive care unit (ICU) patients with notable extensive-drug resistance ability. The study investigates carbapenemase producing A. baumannii strains exhibiting an extensively drug-resistant (XDR) phenotype, isolated from ICU patients in Khartoum. Methods: A total of 100 nonduplicate Gram-negative coccobacilli strains were obtained from microbiology laboratory of ICU patients’ clinical isolates. Molecular identification of A. baumannii was performed by targeting 16S rRNA gene using specifically designed primers. Then, XDR strains were determined by susceptibility testing (disc diffusion). For detection of carbapenemase genes Polymerase chain reaction (PCR) was carried out. Result: Of 100 ICU clinical isolates, 38 (38.0%) was confirmed A. baumannii strains, those strains showed 100% carbapenem resistance and 60.5% extensive drug resistance to the antibiotics tested. The frequency of carbapenemase producer was 57.9% (22/38) of carbapenem resistance A. baumannii (CRAB). The most common carbapenemase associated with resistance was blaOXA gene followed by blaNDM and blaGES A. baumannii isolates. The co-occurrence of blaOXA-48-like and blaNDM, blaOXA-23-like and blaOXA-51, and blaNDM-1 and blaOXA-51 was detected in 22.7%, 18.2% strains and 4.5% respectively. A unique characteristic of our findings was the coharbouring of the genes blaNDM-1, blaOXA-23-like, blaOXA-51 and blaOXA-143 in 9.1% strains (2/22), and this was the first report in the Khartoum city, Sudan. Conclusion: We have demonstrated for the first time a high prevalence of XDR-carbapenemase producing A. baumannii clinical isolates from ICU patients in Khartoum. Also an emergent blaOXA-143 was reported as High-Risk Clones. This highlights the routine mentoring of XDR-carbapenemase producing A. baumannii to avoid clone dissemination in our region hospitals.
文摘Tuberculosis (TB), caused by Mycobacterium tuberculosis is an infectious deadly disease and the treatment of which is one of the most severe challenges at the global level. Currently more than 20 chemical medications are described for the treatment of TB. Regardless of availability of several drugs to treat TB, the causative agent, M. tuberculosis is nowadays getting resistant toward the conventional drugs and leading to conditions known as Multidrug-resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB). This situation has terrified the global health community and raised a demand for new anti-tuberculosis drugs. Medicinal plants have been used to cure different common as well as lethal diseases by ancient civilizations due to its virtue of variety of chemical compounds which may have some important remedial properties. The aim of the present review is to focus the anti-tubercular medicinal plants native to India as well as the plants effective against MDR or XDR-TB across the globe. In the present review, we have addressed 25 medicinal plants for TB and 16 plants effective against MDR-TB testified from India and 23 herbal plants described for MDR-TB across the world during 2011-2015. These herbal plants can serve as promising candidates for developing novel medications to combat multidrug resistant M. tuberculosis.
文摘India tops the global list for Drug resistant Tuberculosis, but inadequate and expensive laboratory culture techniques have led to delay in the diagnosis and treatment. We studied the potential of an alternative method which could be cost-effective by combining the drugs in the same tube for identification of drug resistance. Drug Susceptibility Test (DST) results of 1000 sputum samples are got from suspected TB patients against INH (isoniazid) and Rifampicin by two techniques: a) a modified technique with both drugs in the same MGIT tube and b) a standard technique with the antibiotics in separate MGIT tubes for the diagnosis of MDR-TB (Multidrug Resistant). 39 samples were contaminated and were excluded from final analysis. 198 were smear positives by the concentrated Ziehl-Neelsen’s staining method. 219 were found to be culture positive out of which 195 were identified as M. tuberculosis complex. 40 (20.5%) strains were identified as MDR-TB by the conventional method and 39 were picked up by the modified DST. INH and Rifampicin mono-resistance accounted for 32 (16.4%) and 4 (2%) respectively. 99% concordance was observed between the two tests in categorizing MDR-TB. Similarly modified technique with combination of the second line Antibiotics-Ofloxacin, Kanamycin and Capreomycin was applied on the identified MDR strains in a stepwise manner. 6 (15%) were identified as Pre-XDR strains and 2 (5%) were found to be XDR-TB strains. This study implies that combining drugs in the same tube may be an equivalent and possibly a cost-effective alternative which needs to be explored further.
文摘Several related substances were detected at trace level in (2R)-2,3-dihydro-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl] phenoxy] methyl]imidazo[2, 1-b]oxazole drug substance by a newly developed high-performance liquid chromatography method. All related substances were characterized rapidly but some impurities were found to be intermediates. Proposed structures were further confirmed by characterization using NMR, FT-IR, and HRMS techniques. Based on the spectroscopic data;unknown related sub-stances were characterized as 1-(Methylsulfonyl)-4-[4-(trifluoromethoxy) phenoxy]piperidine;4-{4-[4-(Tri-fluoromethoxy)-phenoxy]piperidin-1-yl}phenol and 4-{4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl}phenyl methane sulfonate;4-Bromophenyl methane sulfonate, Ethyl 3,6-dihydro-1(2H)-pyridine carboxylate, (2S)-3-(4-Bromophenoxy)-2-hydroxy-2-methylpropyl methane sulfonate, (2S)-3-(4-Bromophenoxy)-2-methylpropane-1,2-diyldimethane-sulfonate, (2S)-2-Methyl-3-(4-{4-[4-(trifluoromethoxy) phenoxy]-piperidin-1-yl} phenoxy)-propane-1,2-diyldimethane sulfonate, (S)-3-(4-Bromophenoxy)-2-methyl-propane-1,2-diol and corresponding Enantiomer, (2R)-2-[(4-Bromo-phenoxy)methyl]-2-methyloxirane and (2R)-2-[(4-bromophenoxy)methyl]-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole. A possible mechanism for the formation of these related substances is also proposed.
文摘Objectives: Bedaquiline (BDQ) is the first new anti-tuberculosis (TB) drug introduced to the market after 45 years. Recent studies have shown the potential benefits of adding bedaquiline to regimens for drug-resistant TB (DR-TB). In search of more effective regimens for DR-TB, bedaquiline was introduced in the TB program in the Philippines under operational research to assess its effectiveness, safety, and tolerability when given with background regimens among patients with multi-or extensively DR-TB (MDR/XDR-TB). Design: A prospective cohort study of patients with MDR/XDR-TB was given with a bedaquiline-containing regimen from June 2016 to May 2017. Demographic data, presence of comorbidities, and microbiologic profile on entry were recorded. Bedaquiline was administered at the recommended dose of 400 mg once daily for 14 days, then 200 mg three times a week for 22 weeks together with World Health Organization (WHO)-compliant background regimen. The time to culture conversion, interim outcomes at the 6th month of treatment, end-of-treatment outcomes, and post-treatment follow-up outcomes after one year was determined. The frequency and severity of adverse events (SAE) were recorded as part of pharmacovigilance. Results: Seventy-five patients were given with bedaquiline-containing regimen during the study period. Forty-two (56.0%) had second-line injectable resistance, 23 (30.7%) had fluoroquinolone-resistance, 6 (8.0%) had MDR-TB, and 4 (5.3%) had XDR-TB. In the 6th month of post-enrolment, 79% were culture-negative. The treatment success rate was 65.3% (37 were cured and 12 completed treatment), 7 (9.3%) died, 17 (22.7%) lost to follow-up, and 2 (2.7%) were withdrawn from treatment. Adverse events included vomiting (80%), dizziness (69%), nausea (52%), cough (44%), and headache (36%). The post-treatment follow-up of 49 patients in the 12th month showed 92% were culture-negative while 8% of TBC were not done. Conclusion: Bedaquiline-containing regimens for patients with MDR/XDR-TB were highly effective with an acceptable safety profile and favorable treatment outcomes, but the proportion of patients who lost to follow-up remains substantial.
文摘Rifampicin-resistant tuberculosis (RR-TB) is a global public health problem caused by mycobacterium tuberculosis resistant to Rifampicin. Drug-induced peripheral neuropathy and neurotoxicity are well-known adverse effects of treatment regimens that cause significant morbidity. Pyridoxine is often added to treatment regimens for the prevention and/or treatment of these side effects. The basis and effectiveness of this practice are unclear. We conducted a systematic review to evaluate the effectiveness of pyridoxine in preventing and/or treating neuropathy and neurotoxicity associated with RR-TB treatment. We included studies with patients with RR-TB who experienced neuropathy or neurotoxicity attributed to RR-TB regimens and were given pyridoxine. Our findings showed contradicting evidence on the use of pyridoxine for preventing or treating neurotoxicity due to cycloserine in the treatment of RR-TB. Moreover, pyridoxine did not have a protective effect against neuropathy and/or neurotoxicity caused by other RR-TB regimens that do not contain isoniazid. In conclusion, we found that withdrawing or withholding medications such as linezolid, cycloserine, thioamides, fluoroquinolones, and ethambutol, implicated in causing neuropathy or neurotoxicity was more effective than using pyridoxine to stop the progression of symptoms, and in some instances, led to their reversal over time.
