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Journal of Microbiological Methods Jun 2022Neisseria gonorrhoeae is a major concern of public health due to its extraordinary capacity to develop and acquire resistance to different antimicrobials used to treat...
INTRODUCTION
Neisseria gonorrhoeae is a major concern of public health due to its extraordinary capacity to develop and acquire resistance to different antimicrobials used to treat gonorrhoea. Limited treatment options and uncontrolled transmission have raised the need to assess the antimicrobial susceptibility profile of the isolates and to establish affordable alternatives for laboratory diagnosis.
OBJECTIVES
This study aimed to (i) determine the susceptibility profile of 336 clinical isolates of N. gonorrhoeae to ceftriaxone, azithromycin, ciprofloxacin, spectinomycin and gentamicin by the gold standard agar dilution method; (ii) assess the agreement among agar dilution and disc diffusion results for ciprofloxacin, azithromycin, ceftriaxone, spectinomycin and gentamicin.
RESULTS
All isolates were susceptible to ceftriaxone and spectinomycin. The levels of resistance to azithromycin and ciprofloxacin were 3.9% and 35.1%, respectively. Intermediate susceptibility to gentamicin was observed in 19.4% of isolates. There was 100% agreement between methods for spectinomycin and ceftriaxone, 99.7% for ciprofloxacin, and 85.7% for azithromycin. For gentamicin, there was 86.3% agreement between agar dilution and disc diffusion, resulting in intermediate susceptible by one method and susceptible by the other method, defined as minor errors. The discordance among agar dilution and disc diffusion results is acceptable for ciprofloxacin, ceftriaxone and spectinomycin as per CLSI M23-Ed4.
CONCLUSIONS
Spectinomycin and gentamicin can be considered in some cases as options for the treatment of gonorrhoea in Brazil. Disc diffusion can be an alternative method in routine testing with comparable accuracy to agar dilution.
Topics: Agar; Anti-Bacterial Agents; Azithromycin; Ceftriaxone; Ciprofloxacin; Gentamicins; Gonorrhea; Humans; Microbial Sensitivity Tests; Neisseria gonorrhoeae; Spectinomycin
PubMed: 35526670
DOI: 10.1016/j.mimet.2022.106480 -
Frontiers in Microbiology 2022A novel chromosome-encoded aminoglycoside -nucleotidyltransferase AadA33 was identified in strain P13. The AadA33 shares the highest amino acid identity of 51.28% with...
A novel chromosome-encoded aminoglycoside -nucleotidyltransferase AadA33 was identified in strain P13. The AadA33 shares the highest amino acid identity of 51.28% with the function characterized AadA31. Antibiotic susceptibility testing and enzyme kinetics analysis revealed that the function of AadA33 is to mediate spectinomycin and streptomycin resistance. The recombinant strain harboring (pUCP20-/ DH5α) displayed >256- and 128-fold increases in the minimum inhibitory concentration levels to spectinomycin and streptomycin, respectively, compared with the control strains pUCP20/DH5α. Enzyme kinetic parameters manifested the substrate of AadA33 including spectinomycin and streptomycin, with / of 3.28 × 10 (M s) and 3.37 × 10 (M s), respectively. Bioinformatics analysis revealed its structural mechanism of antimicrobial resistance, genetic context, and phylogenetic relationship with other aminoglycoside -nucleotidyltransferases. This study of AadA33 contributed to understanding the function and resistance mechanism of aminoglycoside -nucleotidyltransferase.
PubMed: 36177473
DOI: 10.3389/fmicb.2022.990739 -
The Journal of Infectious Diseases Jul 2017Mycoplasmagenitalium is an important sexually transmitted pathogen responsible for both male and female genital tract disease. Appreciation of its significance in human... (Review)
Review
Mycoplasmagenitalium is an important sexually transmitted pathogen responsible for both male and female genital tract disease. Appreciation of its significance in human disease has been hampered by its slow growth in culture, difficulty in isolating it, and lack of commercial molecular-based tests for rapid detection. Comparatively few in vitro data on antimicrobial susceptibility are available due to the scarcity of clinical isolates and difficulty in performing susceptibility tests to determine minimum inhibitory concentrations for M. genitalium. Antimicrobial agents that inhibit protein synthesis such as macrolides, along with fluoroquinolones that inhibit DNA replication, have been the treatments of choice for M. genitalium infections. Even though international guidelines recommend azithromycin as first-line treatment, rapid spread of macrolide resistance as well as emergence of quinolone resistance has occurred. Increasing rates of treatment failure have resulted in an urgent need for new therapies and renewed interest in other classes such as aminocyclitols, phenicols, and streptogramins as treatment alternatives. Limited data for new investigational antimicrobials such as the ketolide solithromycin suggest that this drug may eventually prove useful in management of some resistant M. genitalium infections, although it is not likely to achieve cure rates >80% in macrolide-resistant strains, in a similar range as recently reported for pristinamycin. However, agents with completely new targets and/or mechanisms that would be less likely to show cross-resistance with currently available drugs may hold the greatest promise. Lefamulin, a pleuromutilin, and new nonquinolone topoisomerase inhibitors are attractive possibilities that require further investigation.
Topics: Anti-Bacterial Agents; Azithromycin; Drug Discovery; Drug Resistance, Bacterial; Female; Fluoroquinolones; Humans; Male; Microbial Sensitivity Tests; Mycoplasma Infections; Mycoplasma genitalium; Quinolines; Spectinomycin; Streptogramins; Tetracyclines; Thiamphenicol; Treatment Failure
PubMed: 28838073
DOI: 10.1093/infdis/jix132 -
Toxicology Reports 2022This study aimed to investigate the nonclinical safety of lincomycin and spectinomycin hydrochloride (LC-SPH) intramuscular (i.m) doses on target animals (chickens) to...
This study aimed to investigate the nonclinical safety of lincomycin and spectinomycin hydrochloride (LC-SPH) intramuscular (i.m) doses on target animals (chickens) to provide guidelines for dose level design and side effect monitoring in clinical trials. A total of 80 healthy Arbor Acres plus broiler chicks were completely randomized and blindly divided into four treatment groups (control, one-time dose, three-time dose, and five-time dose) of 20 chicks each (20 chickens per group). At the age of day 15, all chickens (except the control group) were administered LC-SPH intramuscularly (chest muscles) at different doses of 20 mg/kg.bw, 60 mg/kg.bw, and 100 mg/kg.bw respectively for 9 consecutive days recommended by veterinary international cooperation on harmonization (VICH) guidelines. The chickens had ad libitum access to antibiotic-free feed and water. Feeding chickens were observed twice a day throughout the study. The drug safety was evaluated by complete blood count, biochemical parameters, histopathological, clinical signs, body weight gain, and feed conversion ratio (FCR). Hence, considering the minor toxicity of 60 mg/kg, our results reveal that intramuscular injection of at least 20 mg/kg body weight has no effects on growth performance, clinical blood parameters, organ coefficient, and histopathological parameters. Thus, a combination of LC-SPH 20 mg/kg body weight i.m injection investigated safe followed daily administration for nine consecutive days in healthy chickens. It is concluded that the experimental results support the safety of 20 mg/kg body weight in combination for the further clinical research study.
PubMed: 35169546
DOI: 10.1016/j.toxrep.2022.01.012 -
Survey of Ophthalmology 1987Gonococcal keratoconjunctivitis is a potentially devastating infection, because Neisseria gonorrhoeae can cause a rapid, severe, ulcerative keratitis resulting in visual... (Review)
Review
Gonococcal keratoconjunctivitis is a potentially devastating infection, because Neisseria gonorrhoeae can cause a rapid, severe, ulcerative keratitis resulting in visual loss. The therapeutic decision making process is complicated by the necessity for prompt, effective parenteral therapy, frequent coinfection with other sexually transmitted diseases, and emergence of antibiotic resistance. Because of the evolving problem of antibiotic resistance and the need for cost containment, the current recommendations of hospitalization for intravenous penicillin may need to be modified. The third generation cephalosporin, ceftriaxone, has properties that suggest it may be the best available antimicrobial agent as a single-dose treatment of gonococcal conjunctivitis. Spectinomycin may be a useful alternative in the penicillin-allergic adult patient.
Topics: Adult; Anti-Bacterial Agents; Cephalosporins; Gonorrhea; Humans; Infant, Newborn; Keratoconjunctivitis; Penicillin G; Spectinomycin
PubMed: 2965423
DOI: 10.1016/0039-6257(87)90095-6 -
The Journal of Antibiotics Jun 2021Spectinomycin, an aminocyclitol antibiotic, is subject to inactivation by aminoglycoside modifying enzymes (AMEs) through adenylylation or phosphorylation of the...
Spectinomycin, an aminocyclitol antibiotic, is subject to inactivation by aminoglycoside modifying enzymes (AMEs) through adenylylation or phosphorylation of the 6-hydroxy group position. In this study, the effects of deoxygenation of the 2- and 6-hydroxy group positions on the spectinomycin actinamine ring are probed to evaluate their relationship to ribosomal binding and the antimicrobial activities of spectinomycin, semisynthetic aminomethyl spectinomycins (amSPCs), and spectinamides. To generate these analogs, an improved synthesis of 6-deoxyspectinomycin was developed using the Barton deoxygenation reaction. 6-Dehydrospectinamide was also synthesized from spectinamide 4 to evaluate the H-bond acceptor character on the C-6 position. All the synthesized analogs were tested for antibacterial activity against a panel of Gram (+) and Gram (-) pathogens, plus Mycobacterium tuberculosis. The molecular contribution of the 2- and 6-hydroxy group and the aryl functionalities of all analogs were examined by measuring inhibition of ribosomal translation and molecular dynamics experiments with MM/GBSA analysis. The results of this work indicate that the 6-hydroxy group, which is the primary target of AMEs, is a required motif for antimicrobial activity in current analogs. Removal of the 6-hydroxy group could be partially rescued by offsetting ribosomal binding contributions made by the aryl side chains found in the spectinamide and amSPCs. This study builds on the knowledge of the structure-activity relationships of spectinomycin analogs and is being used to aid the design of next-generation spectinomycins.
Topics: Anti-Bacterial Agents; Bacterial Proteins; Microbial Sensitivity Tests; Molecular Dynamics Simulation; Mycobacterium tuberculosis; Ribosomes; Spectinomycin; Structure-Activity Relationship
PubMed: 33504919
DOI: 10.1038/s41429-021-00408-3 -
Gut Pathogens Jan 2022Enterococcus cecorum (EC) is one of the main reasons for skeletal disease in meat type chickens. Intervention strategies are still rare and focus mainly on early...
BACKGROUND
Enterococcus cecorum (EC) is one of the main reasons for skeletal disease in meat type chickens. Intervention strategies are still rare and focus mainly on early antibiotic treatment of the disease, although there are no data available concerning the effectivity of this procedure. The present study aimed to investigate the effectivity of early lincomycin-spectinomycin treatment during the first week of life after EC-infection. Furthermore, the impact of lincomycin-spectinomycin treatment and EC infection on the development of cecal microbiota was investigated.
METHODS
A total of 383 day-old broiler chicks were randomly assigned to four groups (non-infected and non-treated, non-infected and treated, EC-infected and non-treated, and EC-infected and treated). The EC-infected groups were inoculated orally with an EC suspension at the day of arrival and at study day 3. The treatment groups were treated with lincomycin-spectinomycin via the drinking water for six consecutive days, starting two hours after the first inoculation. Necropsy of 20 chickens per group was performed at study days 7, 14, 21, and 42. Bacteriological examination via culture and real-time PCR was performed to detect EC in different extraintestinal organs. Cecal samples of nine chickens per group and necropsy day were analyzed to characterize the composition of the cecal microbiota.
RESULTS
No clinical signs or pathologic lesions were found at necropsy, and EC was not detected in extraintestinal organs of the EC-infected and treated birds. Lincomycin-spectinomycin promoted the growth of the bacterial genus Escherichia/Shigella and reduced the amount of potentially beneficial Lactobacillus spp. in the ceca regardless of EC-infection. Unexpectedly, the highest abundances of the genus Enterococcus were found directly after ending antibiotic treatment in both treatment groups, suggesting the growth of resistant enterococcal species. EC was not detected among the most abundant members of the genus Enterococcus. Oral EC-infection at the first day of life did not influence the development of cecal microbiota in the present study.
CONCLUSIONS
Lincomycin-spectinomycin treatment during the first week of life can prevent the EC-associated disease in broiler type chickens and has a direct impact on the development of the cecal microbiota. The low abundance of EC in the ceca of infected chickens underlines the pathogenic nature of the disease-causing EC strains. Further research on alternative prevention and intervention strategies is needed with regard to current efforts on reducing the use of antibiotics in livestock animals.
PubMed: 34983636
DOI: 10.1186/s13099-021-00467-9 -
Plant Physiology Sep 2017Plastid transformation is routine in tobacco () but 100-fold less frequent in Arabidopsis (), preventing its use in plastid biology. A recent study revealed that null...
Plastid transformation is routine in tobacco () but 100-fold less frequent in Arabidopsis (), preventing its use in plastid biology. A recent study revealed that null mutations in , encoding a plastid-targeted acetyl-coenzyme A carboxylase, cause hypersensitivity to spectinomycin. We hypothesized that plastid transformation efficiency should increase in the background, because when ACC2 is absent, fatty acid biosynthesis becomes dependent on translation of the plastid-encoded ACC β-carboxylase subunit. We bombarded -defective Arabidopsis leaves with a vector carrying a selectable spectinomycin resistance () gene and , encoding the green fluorescence protein GFP. Spectinomycin-resistant clones were identified as green cell clusters on a spectinomycin medium. Plastid transformation was confirmed by GFP accumulation from the second open reading frame of a polycistronic messenger RNA, which would not be translated in the cytoplasm. We obtained one to two plastid transformation events per bombarded sample in spectinomycin-hypersensitive Slavice and Columbia knockout backgrounds, an approximately 100-fold enhanced plastid transformation frequency. Slavice and Columbia are accessions in which plant regeneration is uncharacterized or difficult to obtain. A practical system for Arabidopsis plastid transformation will be obtained by creating an null background in a regenerable Arabidopsis accession. The recognition that the duplicated ACCase in Arabidopsis is an impediment to plastid transformation provides a rational template to implement plastid transformation in related recalcitrant crops.
Topics: Acetyl-CoA Carboxylase; Arabidopsis; Arabidopsis Proteins; Gene Transfer Techniques; Genetic Vectors; Microscopy, Confocal; Plastids; Transformation, Genetic
PubMed: 28739820
DOI: 10.1104/pp.17.00857 -
The Cochrane Database of Systematic... Feb 2018Gonorrhoea is a sexually transmitted infection that is caused by Neisseria gonorrhoeae, and is a major public health challenge today. N gonorrhoeae can be transmitted... (Review)
Review
BACKGROUND
Gonorrhoea is a sexually transmitted infection that is caused by Neisseria gonorrhoeae, and is a major public health challenge today. N gonorrhoeae can be transmitted from the mother's genital tract to the newborn during birth, and can cause gonococcal ophthalmia neonatorum as well as systemic neonatal infections. It can also cause endometritis and pelvic sepsis in the mother. This review updates and replaces an earlier Cochrane Review on antibiotics for treating this infectious condition.
OBJECTIVES
To assess the clinical effectiveness and harms of antibiotics for treating gonorrhoea in pregnant women.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2017), LILACS database (1982 to April 5, 2017), the WHO International Clinical Trials Registry Platform (ICTRP; April 5, 2017), ClinicalTrials.gov (April 5, 2017), the ISRCTN Registry (April 5, 2017), and Epistemonikos (April 5, 2017). We also searched reference lists of all retrieved articles.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing the use of antibiotics for treating gonorrhoea in pregnancy. The antibiotics could have been used alone or in combination, were administered parenterally, orally, or both, and were compared with another antibiotic.We included RCTs regardless of their publication status (published, unpublished, published as an article, an abstract, or a letter), language, or country. We applied no limits on the length of follow-up.We excluded RCTs using a cluster- or cross-over design, or quasi-RCTs.
DATA COLLECTION AND ANALYSIS
Three review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked them for accuracy.
MAIN RESULTS
We included two RCTs, that randomised 514 pregnant women (347 women analysed) at a mean gestational age of 22 weeks. Both trials were conducted in the outpatient department of the same two hospitals in the USA between 1993 and 2001, and had a follow-up of 14 days. One of the trials was sponsored by a drug company. We considered both trials to be at a high risk of bias.One trial compared ceftriaxone (125 mg, intramuscular) with cefixime (400 mg, oral); the other trial had three arms, and assessed ceftriaxone (250 mg, intramuscular) versus either amoxicillin (3 g, oral) plus probenecid (1 g, oral) or spectinomycin (2 g, intramuscular). We did not include the spectinomycin data because this medication is no longer produced. We were unable to conduct meta-analysis because the trials compared different medications.We found inconclusive evidence that there were clear differences in the cure of gonococcal infections (genital, extragenital, or both) between intramuscular ceftriaxone versus oral amoxicillin plus oral probenecid (risk ratio (RR) 1.07, 95% confidence interval (CI) 0.98 to 1.16; one RCT; 168 women; very low-quality evidence) or intramuscular ceftriaxone versus oral cefixime (RR 0.99, 95% CI 0.91 to 1.08; one RCT; 95 women; very low-quality evidence).Neither of the trials reported on two of this review's primary maternal outcomes: incidence of obstetric complications (miscarriage, premature rupture of membranes, preterm delivery, or fetal death), or disseminated gonococcal infection, or on the incidence of neonatorum ophthalmia in the neonates.One trial reported one case of vomiting in the oral amoxacillin plus probenecid group. Trials reported pain at the injection sites, but did not quantify it. Hyperberbilurrubinemia was more frequent in neonates whose mothers were exposed to ceftriaxone. There were no clear differences between groups for neonatal malformation.
AUTHORS' CONCLUSIONS
This Cochrane Review found high levels of cure of gonococcal infections in pregnancy with the given antibiotic regimens. However, the evidence in this review is inconclusive as it does not support one particular regimen over another. This conclusion was based on very low-quality evidence (downgraded for poor trial design, imprecision) from two trials (involving 514 women), which we assessed to be at a high risk of bias for a number of domains. The harm profiles of the antibiotic regimes featured in this review remain unknown.High-quality RCTs are needed, with sufficient power to assess the clinical effectiveness and potential harms of antibiotics in pregnant women with gonorrhoea. These should be planned according to Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT),conducted following CONSORT recommendations, and based on Patient-Centered Outcomes Research Institute (PCORI) outcomes.
Topics: Amoxicillin; Anti-Bacterial Agents; Cefixime; Ceftriaxone; Female; Gonorrhea; Humans; Pregnancy; Pregnancy Complications, Infectious; Probenecid; Randomized Controlled Trials as Topic; Spectinomycin
PubMed: 29465747
DOI: 10.1002/14651858.CD011167.pub2 -
Frontiers in Cellular and Infection... 2022Despite reinvigorated efforts in Tuberculosis (TB) drug discovery over the past 20 years, relatively few new drugs and candidates have emerged with clear utility against...
Despite reinvigorated efforts in Tuberculosis (TB) drug discovery over the past 20 years, relatively few new drugs and candidates have emerged with clear utility against drug resistant TB. Over the same period, significant technological advances and learnings around target value have taken place. This has offered opportunities to re-assess the potential for optimization of previously discovered chemical matter against (M.tb) and for reconsideration of clinically validated targets encumbered by drug resistance. A re-assessment of discarded compounds and programs from the "golden age of antibiotics" has yielded new scaffolds and targets against TB and uncovered classes, for example beta-lactams, with previously unappreciated utility for TB. Leveraging validated classes and targets has also met with success: booster technologies and efforts to thwart efflux have improved the potential of ethionamide and spectinomycin classes. Multiple programs to rescue high value targets while avoiding cross-resistance are making progress. These attempts to make the most of known classes, drugs and targets complement efforts to discover new chemical matter against novel targets, enhancing the chances of success of discovering effective novel regimens against drug-resistant TB.
Topics: Humans; Antitubercular Agents; Ethionamide; Spectinomycin; Tuberculosis, Multidrug-Resistant; Tuberculosis; beta-Lactams
PubMed: 36275029
DOI: 10.3389/fcimb.2022.1029044