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Staphylococcus aureus (S. aureus), recognized as one of the deadliest pathogens responsible for nosocomial and community acquired infections, is highly contagious and associated with significant morbidity and mortality. The increasing emergency and rapid spread of various forms of drug-resistant S. aureus have already posed a heavy burden on the world health system, but newfangled antibiotics are right now being created at a much slower pace than our developing requirement. Macrolides could inhibit protein synthesis by targeting the bacterial ribosome and are a class of basic and widely used antibacterial agents in clinical practice to control infections caused by various bacteria, including S. aureus. However, the emergence of bacterial resistance to macrolide antibiotics, particularly in Gram-positive bacteria such as macrolide-resistant S. aureus, has already become one of the significant obstacles for effective chemotherapy. Therefore, there is a critical need for the development of novel macrolide candidates. This review provides an overview of macrolide hybrids with potential activity against S. aureus, including drug-resistant forms developed in the recent decade, with special emphasis on the structure-activity relationships and mechanism of actions.

Macrolides are antibiotics that can be used to treat various infections. Allergic reactions to macrolides are rare, but may include minor to severe skin reactions, as well as systemic life-threatening reactions such as anaphylaxis. Hypersensitivity reactions can occur in any mode of administration and to almost all antibiotics. The purpose of the study was to determine whether there are reactions to macrolides in the study population, and to determine statistically significant differences in the occurrence of allergic reactions to macrolides between boys and girls of the same age and whether there are differences in the occurrence of allergic reactions between respondents in urban and rural areas. The sample consists of 1605 respondents, the sample was randomly selected and stratified by sex, and all data were processed in the statistical program. The results of the research show that 9.1% of the total population of boys and girls aged 15 from the Tuzla Canton are allergic to some type of antibiotic. The percentage of allergic reactions in the total population of 15-year-olds from suburban settlements is slightly higher than among peers in urban areas, but the differences are not statistically significant. A higher rate of allergic reactions was recorded in the group of boys from urban and rural areas. Macrolide allergies were found only in a group of boys in rural areas. This study confirmed that allergies to macrolides are rare and revealed differences in the occurrence of allergic reactions between girls and boys.

Chlamydia trachomatis infection is a public health problem worldwide. Although antibiotic resistance of this strict intracellular bacterium is rare, it is important to monitor the appearance of resistance genes to available efficient antibiotics. This study aimed to screen for mutations in some of these genes in C. trachomatis clinical isolates, which may be associated to resistance to quinolone and macrolide antibiotics. Thirty-five endocervical samples were collected from women aged between 18 and 49 in five district hospitals in the Western Region of Cameroon. The mutations in quinolones (parC and gyrA) and macrolides (L4, L22 and 23S rRNA) resistance domains were detected by PCR followed by sequencing on positive samples to C. trachomatis. The overall mutation rate for the studied genes was 60% in the studied samples. Seven (20%) and twelve (34%) samples presented mutations in the parC and gyrA gene respectively. Mutations in L4 (11.42%) and L22 (60%) were detected in ours samples, while no mutation was found in 23S rRNA gene. Seven clinical samples (20%) presented mutations to both macrolide and quinolone resistance genes. This study revealed a relatively high rate of mutations in the resistance genes to macrolides and quinolones in C. trachomatis in the West Cameroon. This rate of mutation calls for the competent authorities for better surveillance of C. trachomatis infection in West Cameroon to avoid a sudden increase in resistance to antibiotics in the years to come.

Temporomandibular disorders (TMD) are conditions clinically characterized by pain and dysfunction in the masticatory muscles, temporomandibular joints (TMJs), and adjacent structures.The goal of treatment for TMDs is elimination or reduction of pain and maintain normal temporomandibular joint function, preventing further joint damage, and reducing disease-related morbidities. Immediate postoperative intra-articular drugs injections are currently being combined with arthrocentesis to treat both pain and the inflammatory disease process and improve outcomes. The aim of this study was to assess the efficacy of intra-articular injection of macrolides versus corticosteroids in improving outcomes after temporomandibular joint (TMJ) arthrocentesis in internal derangement (ID) of the joint due to anteriorly non reducing disc displacement.The study included 24 patients with internal derangement of the temporomandibular joint who did not respond to conservative treatment for 3 months. Patients were randomly divided into 2 equal groups according to the intra-articular drug injected after arthrocentesis. In group I, a corticosteroid is injected and in group II a macrolide with a known anti-inflammatory effect is used. Pain, mouth opening and analysis of Tumor Necrosis Factor-α (TNF-α) concentration were used as indicators of symptoms alleviation and patients improvement.In both groups, the median pain scores and MMO measurements after three months showed statistically significant lower values compared to pre-operative ones. In Conclusion, intra-articular injection of Azithromycin is comparable to corticosteroids injection as an effective method for treatment of the underlying disease process of internal derangement of the TMJ and alleviation of disease associated symptoms, such as pain and limitation of mouth opening. K

Macrolides have been effective clinical antibiotics for over 70 years. They inhibit protein biosynthesis in bacterial pathogens by narrowing the nascent protein exit tunnel in the ribosome. The macrolide class of natural products consist of a macrolactone ring linked to one or more sugar molecules. Most of the macrolides used currently are semi-synthetic erythromycin derivatives, composed of a 14- or 15-membered macrolactone ring. Rapidly emerging resistance in bacterial pathogens is among the most urgent global health challenges, which render many antibiotics ineffective, including next-generation macrolides. To address this threat and advance a longer-term plan for developing new antibiotics, we demonstrate how 16-membered macrolides overcome erythromycin resistance in clinically isolated Staphylococcus aureus strains. By determining the structures of complexes of the large ribosomal subunit of Deinococcus radiodurans (D50S) with these 16-membered selected macrolides, and performing anti-microbial studies, we identified resistance mechanisms they may overcome. This new information provides important insights toward the rational design of therapeutics that are effective against drug resistant human pathogens.

Mycoplasma pneumoniae is a common pathogen that causes community-acquired pneumonia. In the past, M. pneumoniae was sensitive to macrolide antibiotics, and M. pneumoniae pneumonia (MPP) was usually a benign and self-limiting disease. However, despite use of the appropriate antibiotics, persistent fever and clinical deterioration may occur, leading to severe disease. Two major complicated conditions that may be clinically encountered are macrolide-resistant MPP and refractory MPP. Regarding the epidemics in Taiwan, before 2017, the mean rate of macrolide resistance was below 30%. Notably, since 2018, the prevalence of macrolide-resistant MPP in Taiwan has increased rapidly. Macrolide-resistant MPP shows persistent fever and/or no radiological regression to macrolide antibiotics and may even progress to severe and complicated pneumonia. Tetracyclines (doxycycline or minocycline) or fluoroquinolones are alternative treatments for macrolide-resistant MPP. Refractory MPP is characterized by an excessive immune response against the pathogen. In this context, corticosteroids have been suggested as an immunomodulator for downregulating the overactive host immune reaction. Overuse of macrolides may contribute to macrolide resistance, and thereafter, an increase in macrolide-resistant MPP. Delayed effective antimicrobial treatment is associated with prolonged and/or more severe disease. Thus, the appropriate prescription of antibiotics, as well as the rapid and accurate diagnosis of MPP, is important. The exact starting point, dose, and duration of the immunomodulator are yet to be established. We discuss these important issues in this review.

Background Pertussis, is an infectious respiratory disease caused by Bordetella pertussis. The incidence of pertussis has been increasing in South Korea to due to waning vaccine-induced immunity. Culture has a low sensitivity and a long turnaround time (TAT). Recently, a rapid multi-polymerase chain reaction (mPCR) test with a TAT of about 1 h was developed for the detection of respiratory pathogens (17 viruses and three bacteria), including B. pertussis. This study aimed to investigate the effectiveness of mPCR for early diagnosis and treatment of pertussis. Methods We performed a retrospective study of patients with pertussis diagnosed from May 2017 to June 2019 at a university hospital in South Korea. Nasopharyngeal swab specimens were tested using mPCR. Data were extracted from medical records. Results A total of 27 patients with a median age of 48.9 years (range: 3.3–82.2 years) were diagnosed with pertussis, of whom 9 (33.3%) were male. Eleven (40.7%) had fever, 12 (44.4%) had dyspnea, three (11.1%) had paroxysmal cough, and nine (33.3%) had inspiratory whooping. The median interval from symptom onset to diagnosis was 9.0 days (range: 1–31 days). Twenty-four patients (81.5%) were diagnosed within 2 weeks from symptom onset. All but one patient was prescribed macrolide antibiotics. Twenty-two patients (81.5%) required hospitalization, including three (11.1%) who required intensive care unit care for ventilation. Conclusion Testing patients with respiratory symptoms using mPCR can improve early diagnosis of pertussis, ensure proper treatment, and may help with outbreak control.

OBJECTIVES To describe testing and treatment practices for Mycoplasma pneumoniae (Mp) among children hospitalized with community-acquired pneumonia (CAP). METHODS We conducted a retrospective cohort study using the Pediatric Health Information Systems database. We included children 3 months to 18 years old hospitalized with CAP between 2012 and 2018 and excluded children who were transferred from another hospital and those with complex chronic conditions. We examined the proportion of patients receiving Mp testing and macrolide therapy at the hospital level and trends in Mp testing and macrolide prescription over time. At the patient level, we examined differences in demographics, illness severity (eg, blood gas, chest tube placement), and outcomes (eg, ICU admission, length of stay, readmission) among patients with and without Mp testing. RESULTS Among 103 977 children hospitalized with CAP, 17.3% underwent Mp testing and 31.1% received macrolides. We found no correlation between Mp testing and macrolide treatment at the hospital level (R2 = 0.05; P = .11). Patients tested for Mp were more likely to have blood gas analysis (15.8% vs 12.8%; P < .1), chest tube placement (1.4% vs 0.8%; P < .1), and ICU admission (3.1% vs 1.4%; P < .1). Mp testing increased (from 15.8% to 18.6%; P < .001), and macrolide prescription decreased (from 40.9% to 20.6%; P < .001) between 2012 and 2018. CONCLUSIONS Nearly one-third of hospitalized children with CAP received macrolide antibiotics, although macrolide prescription decreased over time. Clinicians were more likely to perform Mp testing in children with severe illness, and Mp testing and macrolide treatment were not correlated at the hospital level.

Abstract Macrolide antibiotics are one of the most commonly used broad-spectrum antibiotics. They have an inhibitory effect on a variety of respiratory pathogens; besides, they have non-anti-infective effects, including anti-inflammatory, regulating airway secretion, immune regulation, and other effects. A growing number of studies have shown that the non-anti-infective effects of macrolides have important and potential value in the treatment of pediatric chronic airway diseases; the therapy was described as “long-term, low-dose usage”; unfortunately, there is no guideline or consensus that applies to children. To better carry out the mechanism and clinical research of non-anti-infective effect and promote its rational use in children, the authors summarize the evidence of the usage of long-term, low-dose macrolide antibiotic therapy (LLMAT) in the treatment of chronic airway diseases in children and the progress in recent years. Impact This review summarizes the evidence (mostly in recent 5 years) of the usage of long-term, low-dose macrolide antibiotic therapy in the treatment of chronic airway diseases. The recent studies and guidelines support and enrich the point that long-term, low-dose macrolide antibiotic therapy has potential benefit for children with severe asthma, CF, non-CF bronchiectasis, and BO, which provides clinical references and is of clinical interest. Long-term, low-dose macrolide antibiotic therapy has good safety, and no serious events have been reported; however, potential cardiac side effects and macrolide resistance should be clinically noted.

Reactions of the tetraene macrolide antibiotic tetramycin B with p-substituted aromatic aldehydes and sodium cyanoborohydride in the conditions of reaction of reductive amination resulted in formation of its N-benzyl derivatives. Physicochemical and medical and biological properties of obtained derivatives of tetramycin B were studied. Biological investigations showed that N-benzyl derivatives of tetramycin B were low toxic agents and possessed high antifungal activity. The pharmacological tests revealed that the acute toxicity (LD50) of obtained derivatives of tetramycin B was 7–8 times low as that of the starting antibiotic. The automated intellectual information system for optimal choice of the conditions for rational design, synthesis and using in medical practice of novel derivatives of polyene macrolide antibiotics was developed.

Objective To identify patients with Mycoplasma pneumoniae pneumonia (MPP) with a risk of prolonged fever while on macrolides. Methods A retrospective study was performed with 716 children admitted for MPP. Refractory MPP (RMPP-3) was defined as fever persisting for > 72 h without improvement in clinical and radiologic findings after macrolide antibiotics (RMPP-3) or when fever persisted for > 120 h (RMPP-5) without improvement in clinical and radiologic findings. Radiological data, laboratory data, and fever profiles were compared between the RMPP and non-RMPP groups. Fever profiles included the highest temperature, lowest temperature, and frequency of fever. Prediction models for RMPP were created using the logistic regression method and deep neural network. Their predictive values were compared using receiver operating characteristic curves. Results Overall, 716 patients were randomly divided into two groups: training and test cohorts for both RMPP-3 and RMPP-5. For the prediction of RMPP-3, a conventional logistic model with radiologic grouping showed increased sensitivity (63.3%) than the model using laboratory values. Adding laboratory values in the prediction model using radiologic grouping did not contribute to a meaningful increase in sensitivity (64.6%). For the prediction of RMPP-5, laboratory values or radiologic grouping showed lower sensitivities ranging from 12.9 to 16.1%. However, prediction models using predefined fever profiles showed significantly increased sensitivity for predicting RMPP-5, and neural network models using 12 sequential fever data showed a greatly increased sensitivity (64.5%). Conclusion RMPP-5 could not be effectively predicted using initial laboratory and radiologic data, which were previously reported to be predictive. Further studies using advanced mathematical models, based on large-sized easily accessible clinical data, are anticipated for predicting RMPP.

Tyrimo tikslas. Įvertinti antibiotikų sąveiką su vaistais, vartojamais širdies ir kraujagyslių sistemos ligoms (ŠKL) gydyti. Tyrimo uždaviniai. 1. Įvertinti, kokie antibiotikai sąveikauja su vaistais, vartojamais širdies ir kraujagyslių sistemos ligoms gydyti. 2. Nustatyti antibiotikų ir vaistų, vartojamų širdies ir kraujagyslių sistemos ligoms gydyti, sąveikas. Tyrimo metodai. Atlikta 28 mokslinių tyrimų, kuriuose buvo nagrinėta antibiotikų sąveika su vaistais, vartojamais širdies ir kraujagyslių sistemos ligoms gydyti, analizė. Išnagrinėti moksliniai straipsniai, kurių reikšminiai žodžiai: antibiotics, statins, drug-interaction, macrolids, calcium channel blockers, CCB, interraction, citochrome P450, warfarin. Naudotos duomenų bazių (MEDLINE, „PubMed“, EMBASE, „ScienceDirect“, „UpToDate“ ir kt.) paieškos sistemos. Vertinant statinų ir antibiotikų sąveiką, išanalizuota 13 straipsnių nuo 2012 iki 2019 m. Penki straipsniai neatitiko kriterijų. Vertinant kalcio kanalų blokatorių (KKB) ir antibiotikų sąveiką, išanalizuoti šeši straipsniai nuo 2005 iki 2017 m. Vertinant antibiotikų sąveiką su antiaritminiais vaistais ir diuretikais, išnagrinėti aštuoni straipsniai nuo 2003 iki 2019 m. Vertinant antibiotikų sąveiką su digoksinu, buvo nagrinėti septyni straipsniai nuo 1997 iki 2010 m. Vertinant antibiotikų sąveiką su varfarinu, išnagrinėti aštuoni straipsniai nuo 2010 iki 2020 m. Keturi straipsniai neatitiko kriterijų. Nagrinėtų darbų įtraukimo kriterijai: 1) straipsniai publikuoti recenzuojamuose leidiniuose (peer-reviewed); 2) publikuoti visi straipsnių tekstai arba konferencijų tezės; 3) klinikinio tyrimo arba klinikinio atvejo aprašymo tikslas buvo įvertinti antibiotikų sąveiką su vaistais, vartojamais širdies ir kraujagyslių sistemos ligoms gydyti. Straipsnių atmetimo kriterijai: 1) leidiniai nebuvo recenzuojami; 2) vaistų sąveikos nebuvo tyrimo arba klinikinio atvejo aprašo tikslas; 3) straipsniai paskelbti ne anglų ir lietuvių kalbomis (autoriams žinomos kalbos). Išvados. 1. Širdies ir kraujagyslių sistemos ligoms gydyti skiriami vaistai, tokie kaip statinai, kalcio kanalų blokatoriai (ypač nedihidropiridininiai), digoksinas, varfarinas, daugiausia sąveikauja su makrolidų grupės antibiotikais (ypač klaritromicinu bei eritromicinu), nes šie dėl fermento CYP3A4 slopinimo didina širdies ir kraujagyslių sistemos ligoms gydyti skirtų vaistų koncentracijas kraujyje. Azitromicinas, būdamas silpniausias CYP3A4 fermento inhibitorius, daugumoje straipsnių nurodytas kaip mažiausiai su ŠKL gydyti skiriamais vaistais sąveikaujantis makrolidų grupės antibiotikas. 2. Dažniausiai pasitaikančios sąveikos, vartojant makrolidų grupės antibiotikus su statinais, yra rabdomiolizė, mialgija, inkstų bei kepenų funkcijos sutrikimas, su kalcio kanalų blokatoriais – hipotenzija bei jos sąlygotas ūminis inkstų funkcijos nepakankamumas. Makrolidų grupės antibiotikus skiriant su III klasės antiaritminiais vaistais, padidėja torsades de pointes rizika. Pagrindinė vaistų tarpusavio sąveika, vartojant varfariną kartu su antibiotikais, yra tarptautinio normalizuoto santykio reikšmės (INR) padidėjimas, todėl, norint išvengti kraujavimo, reikia skirti antibiotikus, kurie minimaliai sąveikauja su varfarinu (cefaleksinas, klindamicinas), arba trumpinti antibiotikoterapijos kursą, gydymo metu stebėti INR reikšmę. Sąveikos gal ir nedažnos, tačiau gali būti pavojingos gyvybei, todėl, skiriant antibiotikus su ŠKL gydyti vartojamais vaistais, būtina atidi pacientų stebėsena.

Macrolides are among the most widely prescribed antibiotics, particularly for bacterial lung infections, due to their favorable safety, oral bioavailability, and spectrum of activity against Gram-positive pathogens such as Streptococcus pneumoniae, the most common cause of bacterial pneumonia. Their utility against Gram-negative bacteria is extremely limited and does not include the Enterobacteriaceae or other ESKAPE pathogens. With the increasing development of resistance to current therapies and the lack of safe, oral options to treat Gram-negative infections, extended-spectrum macrolides have the potential to provide valuable treatment options. While the bacterial ribosome, the target of macrolides, is highly conserved across Gram-positive and Gram-negative bacteria, traditional macrolides do not possess the proper physicochemical properties to cross the polar Gram-negative outer membrane and are highly susceptible to efflux. As with most natural product-derived compounds, macrolides are generally prepared through semisynthesis, which is limited in scope and lacks the ability to make the drastic physicochemical property changes necessary to overcome these hurdles.By using a fully synthetic platform technology to greatly expand structural diversity, novel macrolides were prepared with a focus on lowering the MW and increasing the polarity to achieve a physicochemical property profile more similar to that of traditional Gram-negative drug classes. In addition to the removal of lipophilic groups, a critical structural feature for obtaining Gram-negative activity in the macrolide class proved to be the introduction of small secondary or tertiary amines to yield polycationic species potentially capable of self-promoted uptake. Within the azithromycin-like 15-membered azalides, potent activity was seen when small alkyl amines were introduced at the 6'-position of desosamine. The biggest gains, however, were made by replacing the entire C10-C13 fragment of the macrolactone ring with commercially available or readily synthesized 1,2-aminoalcohols, leading to 13-membered azalides. The introduction of a tethered basic amine at the C10-position and systematic optimization of substitution and tether length and flexibility ultimately provided new macrolides that for the first time exhibit clinically relevant antibacterial activity against multi-drug resistant Gram-negative bacteria. A retrospective computational analysis of >1800 fully synthetic macrolides prepared during this effort identified key drivers and optimum ranges for improving permeability and avoiding efflux. In contrast to standard Gram-negative drugs which generally have MWs below 600 and clogD7.4 values below 0, we found that the ideal ranges for Gram-negative macrolides were MW between 600 and 720 and cLogD7.4 between -1 and 3. A total charge of between 2.5 and 3 was also required to provide optimal permeability and efflux avoidance. Thus, Gram-negative macrolides occupy a unique physicochemical property space that lies between traditional Gram-negative drug classes and Gram-positive macrolides.

Background Although researchers have found that the microbiota changed during the lower respiratory tract (LRT) infection, little was known about the association between LRT microbiome and refractory M. pneumoniae pneumonia (RMPP). Methods From June 28th, 2019 to March 23rd, 2020, we enrolled fifty-two children diagnosed with RMPP or non-refractory M. pneumoniae pneumonia (NRMPP), and characterized the structure and function of microbiota in the bronchoalveolar lavage fluid (BALF) by metagenomic next generation sequencing (mNGS). Results Based on Bray-Curtis distance between samples, samples in RMPP group were highly homogeneous, and Shannon index in the RMPP group was much lower than NRMPP group while Simpson index, which presents the degree of dominance, was higher in RMPP group. The dominant taxon with relative abundance greater than 50% was merely Mycoplasma among RMPP and NRMPP patients, but the proportions of other taxonomic distribution were different. M. pneumoniae was the dominant species and occupied almost all niches in the vast majority of RMPP patients, whereas the other genera were dramatically lower. The NRMPP group was more enriched in antibiotic resistance genes (ARGs) than the RMPP group, and also exhibited a greater relative abundance of macrolide antibiotics resistance gene (macB) and fluoroquinolone antibiotic resistance genes (patA-B) in M. pneumoniae genome. In RMPP patients, higher relative abundance of Streptococcus pneumoniae had a strong correlation with increased hospitalization days while higher relative abundance of Streptococcus pneumoniae had a negative correlation with hospitalization days among NRMPP patients. Conclusions The microbiota of LRT in children with RMPP was much more homogeneous and simpler than that of the NRMPP group and with lower relative abundance of macrolide antibiotics resistance gene in M. pneumoniae genome. M. pneumoniae was absolutely dominant in the vast majority of RMPP patients. Prolonged hospitalization days was associated with relative abundance of M. pneumoniae in NRMPP patients while it was related with other pathogens' relative abundance (e.g., Streptococcus pneumoniae) in RMPP patients.

This study investigated the transformation kinetics and pathways of four widely used macrolides (MLs), including roxithromycin, azithromycin, erythromycin, and clarithromycin, in dissolved organic ...

Many antibiotics inhibit bacterial growth by binding to the ribosome and interfering with protein biosynthesis. Macrolides represent one of the most successful classes of ribosome-targeting antibiotics. The main clinically relevant mechanism of resistance to macrolides is dimethylation of the 23S rRNA nucleotide A2058, located in the drug-binding site, a reaction catalyzed by Erm-type rRNA methyltransferases. Here, we present the crystal structure of the Erm-dimethylated 70S ribosome at 2.4 A resolution, together with the structures of unmethylated 70S ribosome functional complexes alone or in combination with macrolides. Altogether, our structural data do not support previous models and, instead, suggest a principally new explanation of how A2058 dimethylation confers resistance to macrolides. Moreover, high-resolution structures of two macrolide antibiotics bound to the unmodified ribosome reveal a previously unknown role of the desosamine moiety in drug binding, laying a foundation for the rational knowledge-based design of macrolides that can overcome Erm-mediated resistance. Structural analysis of the A2058-dimethylated and unmethylated 70S ribosome complex alone and in combination with macrolides reveals the role of the desosamine moiety of macrolides in drug binding and resistance.

The prevalence of Shiga toxin-producing Escherichia coli O157 (STEC O157) strains in wild deer and boar in Japan was investigated. STEC O157 strains were isolated from 1.9% (9/474) of the wild deer and 0.7% (3/426) of the wild boar examined. Pulsed-field gel electrophoresis (PFGE) analysis classified the wild deer and boar strains into five and three PFGE patterns, respectively. The PFGE pattern of one wild boar strain was similar to that of a cattle strain that had been isolated from a farm in the same area the wild boar was caught, suggesting that a STEC O157 strain may have been transmitted between wild boar and cattle. Clade analysis indicated that, although most of the strains were classified in clade 12, two strains were classified in clade 7. Whole-genome sequence (WGS) analysis indicated that all the strains carried mdfA, a drug resistance gene for macrolide antibiotics, and also pathogenicity-related genes similar to those in the Sakai strain. In conclusion, our study emphasized the importance of food hygiene in processing meat from Japanese wild animals for human consumption.

One calf died (No. 1) and another was euthanized following astasia (No. 2). Histopathological examination revealed suppurative meningoencephalitis in these calves. Klebsiella pneumoniae antigens were detected in lesions. Thymocytes were decreased in the thymus cortex in both cases. 16S rRNA gene sequencing of the No. 1 isolate and bacterial extracts from formalin fixed paraffin embedded sections of No. 2 revealed that both samples were K. pneumoniae. The No. 1 isolate showed multidrug resistance against penicillin antibiotics, fosfomycin, streptomycin, macrolide antibiotics, tetracycline antibiotics, and clindamycin. Immunosuppression is a significant septicemic K. pneumoniae infection risk factor. Our study provides new aspects regarding K. pneumoniae infections in cattle, bacterial meningoencephalitis differentiation, and K. pneumoniae and bacterial meningoencephalitis treatments.

Introduction. Resistance against macrolide antibiotics in Mycoplasma pneumoniae is becoming non-negligible in terms of both appropriate therapy and diagnostic stewardship. Molecular methods have attractive features for the identification of Mycoplasma pneumoniae as well as its resistance-associated mutations of 23S ribosomal RNA (rRNA). Hypothesis/Gap Statement. The automated molecular diagnostic sytem can identify macrolide-resistant M. pneumoniae . Aim. To assess the performance of an automated molecular diagnostic system, GENECUBE Mycoplasma, in the detection of macrolide resistance-associated mutations. Methodology. To evaluate whether the system can distinguish mutant from wild-type 23S rRNA, synthetic oligonucleotides mimicking known mutations (high-level macrolide resistance, mutation in positions 2063 and 2064; low-level macrolide resistance, mutation in position 2067) were assayed. To evaluate clinical oropharyngeal samples, purified nucleic acids were obtained from M. pneumoniae -positive samples by using the GENECUBE system from nine hospitals. After confirmation by re-evaluation of M. pneumoniae positivity, Sanger-based sequencing of 23S rRNA and mutant typing using GENECUBE Mycoplasma were performed. Results. The system reproducibly identified all synthetic oligonucleotides associated with high-level macrolide resistance. Detection errors were only observed for A2067G (in 2 of the 10 measurements). The point mutation in 23S rRNA was detected in 67 (26.9 %) of 249 confirmed M. pneumoniae -positive clinical samples. The mutations at positions 2063, 2064 and 2617 were observed in 65 (97.0 %), 2 (3.0 %) and 0 (0.0 %) of the 67 samples, respectively. The mutations at positions 2063 and 2064 were A2063G and A2064G, respectively. The results from mutant typing using GENECUBE Mycoplasma were in full agreement with the results from sequence-based typing. Conclusion. GENECUBE Mycoplasma is a reliable test for the identification of clinically significant macrolide-resistant M. pneumoniae .

Community-acquired pneumonia remains one of the most pressing problems in pediatrics. The article presents data on its prevalence, child mortality from this disease, diagnostic criteria and approaches to therapy. In the Russian Federation, respiratory diseases in children aged 0-17 take third place in the structure of causes of death after external causes and malformations. The age characteristics of the etiological spectrum of community-acquired pneumonia in children and the problem of drug resistance of pathogens are discussed in detail. The sharp increase in resistance to macrolide antibiotics of the most common pathogen of the disease in early and pre-school age, pneumococcus, which occurred in recent years, makes it necessary to reconsider the question of the place of these drugs in pediatric practice. At the same time, macrolides remain highly active against atypical pathogens, whose etiological significance increases with age. In this regard, modern indications for prescription of macrolides, unique distinctions of 16-membered josamycin macrolide from other drugs of this series, and mechanisms of its action are reviewed and clarified in the article. Due to the peculiarities of its chemical structure, josamycin remains active against a significant part of pneumococci, which is increasingly resistant to 14- and 15-membered macrolides. The advantages of children’s dosage forms are presented, in particular, the dispersible tablet (solutab). This form, due to controlled release, provides convenience of use, maximum bioavailability (regardless of food intake), minimal frequency of side effects, and does not affect the gastrointestinal motility. Treatment of pneumonia and other respiratory tract infections, especially in young children, is not limited by antibiotics, is always complex and is based on the prevailing syndromes in the clinical picture.

ObjectiveThere is currently no medical treatment proven to limit abdominal aortic aneurysm (AAA) progression. The aim of this systematic review and meta-analysis was to pool data from previous randomised controlled trials assessing the efficacy of blood pressure-lowering and antibiotic medications in limiting AAA growth and AAA-related events, that is, rupture or repair.MethodsA systematic literature search was performed to identify randomised controlled trials that examined the efficacy of blood pressure-lowering medications or antibiotics in reducing AAA growth and AAA-related events. AAA growth (mm/year) was measured by ultrasound or computed tomography imaging. Meta-analyses were performed using random effects models. A subanalysis was conducted including trials that investigated tetracycline or macrolide antibiotics.ResultsTen randomised controlled trials including 2045 participants with an asymptomatic AAA were included. Follow-up was between 18 and 63 months. Neither blood pressure-lowering medications (mean growth±SD 2.0±2.4 vs 2.3±2.7 mm/year; standardised mean difference (SMD) −0.07, 95% CI −0.19 to 0.06; p=0.288) or antibiotics (mean growth±SD 2.6±2.1 vs 2.6±2.5 mm/year; SMD −0.11, 95% CI −0.38 to 0.16; p=0.418) reduced AAA growth or AAA-related events (blood pressure-lowering medications: 92 vs 95 events; risk ratio (RR) 0.86, 95% CI 0.66 to 1.11; p=0.244; and antibiotics: 69 vs 73 events; RR 0.93, 95% CI 0.69 to 1.25; p=0.614). The subanalysis of antibiotics showed similar results.ConclusionsThis meta-analysis suggests that neither blood pressure-lowering medications or antibiotics limit growth or clinically relevant events in people with AAAs.

This review aimed to explore and summarise available cases of delirium suspected to be associated with the use of macrolide antibiotics reported in the literature and the United States Food and Drug Administration's Adverse Event Reporting System (FAERS) database.Electronic searches of the literature were conducted in four online databases: PubMed/MEDLINE, Scopus, Web of Science and Serbian Citation Index (SCIndeks). A search of FAERS database was also conducted to supplement the findings of the literature search. Descriptive statistics, narrative summation and tabulation of the extracted data were made.Cases of delirium which satisfied inclusion criteria were found for clarithromycin, azithromycin, erythromycin and telithromycin. Delirium was described in patients of various age groups, including children. Drug-drug interactions may have contributed to its occurrence in some of the cases. Average time to onset of delirium was 2.5 days for azithromycin and 3.3 days for clarithromycin.Considering that these drugs may be a possible cause of delirium, clinicians should be aware that timely recognition of this possible side effect can lead to earlier discontinuation of the culprit drug, reduce time spent in a delirious state and improve patients' outcomes.KEY POINTSCases of delirium which satisfied inclusion criteria were found for clarithromycin, azithromycin, erythromycin and telithromycin.Cases of delirium were described in patients of various age groups, including children.Drug-drug interactions may have contributed to the occurrence of delirium in some of the cases.Time to onset of delirium ranged from 2 to 3.5 days (mean: 2.5 days) for azithromycin and from 1 to 7 days (mean: 3.3 days) for clarithromycin.Cessation of the macrolide antibiotic seems to be the best management strategy, although some of the patients may, in addition, require antipsychotics.

The growing challenge of microbial resistance emphasizes the importance of new antibiotics or reviving strategies for the use of old ones. Macrolide antibiotics are potent bacterial protein synthesis inhibitors with a formidable capacity to treat life-threatening bacterial infections; however, acquired and intrinsic resistance limits their clinical application. In the work presented here, we reveal that bicarbonate is a potent enhancer of the activity of macrolide antibiotics that overcomes both acquired and intrinsic resistance mechanisms. With a focus on azithromycin, a highly prescribed macrolide antibiotic, and using clinically relevant pathogens, we show that physiological concentrations of bicarbonate overcome drug resistance by increasing the intracellular concentration of azithromycin. We demonstrate the potential of bicarbonate as a formulation additive for topical use of azithromycin in treating a murine wound infection caused by

In analyzing the drug resistance phenotype and mechanism of resistance to macrolide antibiotics of clinical Pseudomonas aeruginosa isolates, the agar dilution method was used to determine the minimum inhibitory concentrations (MICs), and PCR (polymerase chain reaction) was applied to screen for macrolide antibiotics resistance genes. The macrolide antibiotics resistance genes were cloned, and their functions were identified. Of the 13 antibiotics tested, P. aeruginosa strains showed high resistance rates (ranging from 69.5–82.1%), and MIC levels (MIC90 > 256 μg/ml) to macrolide antibiotics. Of the 131 known macrolide resistance genes, only two genes, mphE and msrE, were identified in 262 clinical P. aeruginosa isolates. Four strains (1.53%, 4/262) carried both the msrE and mphE genes, and an additional three strains (1.15%, 3/262) harbored the mphE gene alone. The cloned msrE and mphE genes conferred higher resistance levels to three second-generation macrolides compared to two first-generation ones. Analysis of MsrE and MphE protein polymorphisms revealed that they are highly conserved, with only 1–3 amino acids differences between the proteins of the same type. It can be concluded that even though the strains showed high resistance levels to macrolides, known macrolide resistance genes are seldom present in clinical P. aeruginosa strains, demonstrating that a mechanism other than this warranted by the mphE and msrE genes may play a more critical role in the bacteria’s resistance to macrolides.

Objective Macrolide antibiotics are among the most commonly used antibiotics; the association of macrolide antibiotics exposure with sensorineural hearing loss (SNHL) has been hypothesized. A systematic search was conducted in PubMed, EMBASE and Cochrane Library from inception to 15 July 2019 to identify studies used macrolide antibiotics for any indication. The results were reported as odds ratio (OR) with 95% confidence interval (CI) using random-effects model to derive the association of macrolide antibiotics exposure with SNHL. The objective of this meta-analysis was to estimate the association of macrolide antibiotics exposure and SNHL from up-to-date evidence. Key findings Nine studies met the inclusion criteria. There was no statistically significant association between macrolide antibiotics exposure and SNHL; the OR was 1.20 (95% CI: 0.96 to 1.49). No significant association was found with any of the subgroup meta-analyses. Summary Whilst the frequency of SNHL was higher with macrolide antibiotics exposure compared with controls, overall, no association was found between macrolide antibiotics and SNHL.

Approximately 1.7 million Americans develop hospital associated infections each year, resulting in more than 98,000 deaths. One of the main contributors to such infections is the Gram-negative pathogen Acinetobacter baumannii. Recently, it was reported that aryl 2-aminoimidazole (2-AI) compounds potentiate macrolide antibiotics against a highly virulent strain of A. baumannii, AB5075. The two lead compounds in that report increased clarithromycin (CLR) potency against AB5075 by 16-fold, lowering the minimum inhibitory concentration (MIC) from 32 to 2 μg/mL at a concentration of 10 μM. Herein, we report a structure-activity relationship study of a panel of derivatives structurally inspired by the previously reported aryl 2-AI leads. Substitutions around the core phenyl ring yielded a lead that potentiates clarithromycin by 64- and 32-fold against AB5075 at 10 and 7.5 μM, exceeding the dose response of the original lead. Additional probing of the amide linker led to the discovery of two urea containing adjuvants that suppressed clarithromycin resistance in AB5075 by 64- and 128-fold at 7.5 μM. Finally, the originally reported adjuvant was tested for its ability to suppress the evolution of resistance to clarithromycin over the course of nine consecutive days. At 30 μM, the parent compound reduced the CLR MIC from 512 to 2 μg/mL, demonstrating that the original lead remained active against a more CLR resistant strain of AB5075.

ZusammenfassungPertussis wird durch das gramnegative Bakterium Bordetella pertussis verursacht. Die Krankheitsmanifestationen reichen von unspezifischem Husten bis zu lebensbedrohlichen Verläufen mit Hyperleukozytose und respiratorischer Insuffizienz, v.a. bei jungen Säuglingen. Die Diagnose basiert auf klinischer Symptomatik und mikrobiologischen Nachweisverfahren. Die Therapie besteht aus Makrolidantibiotika; bei Apnoen kann Koffein versucht werden. Die Inzidenz beträgt 10–40 Fälle/100.000 Bevölkerung und Jahr, bei Säuglingen ist sie am höchsten (ca. 50), gefolgt von Jugendlichen (30–35). Mehr als 50 % der in den ersten 5 Lebensmonaten an Pertussis erkrankten Kinder werden hospitalisiert. Die Impfprävention umfasst Grundimmunisierung und regelmäßige Auffrischimpfungen mit azellulären Impfstoffen. Um schwere Verläufe bei jungen Säuglingen zu verhindern, ist die Impfung schwangerer Frauen am erfolgversprechendsten. Säuglinge geimpfter Mütter sollen zeitgerecht ab dem Alter von 2 Monaten für den Eigenschutz immunisiert werden.

Macrolides are clinically well-established class of antibiotics. Macrolides induce cardiotoxicity by blocking ether-a-go-go–related gene (ERG) potassium channels in cardiac myocytes. The aim of this study was to compare the effects of erythromycin, clarithromycin and azithromycin on cell viability and expression of ERG1 gene in H9c2 cells. Cell viability and ERG1 gene expression of H9c2 cells in 3 different concentrations, 1, 10 and 25 µg/ml, after 48 and 72 h were determined by MTT test and Real time-PCR method respectively. After 48 h, the growth of H9c2 cells treated with erythromycin, clarithromycin and Azithromycin (except two doses) were inhibited significantly compared to control group (p

Objective: The current investigation was designed to point out the prevalence of multidrug-resis¬tant Streptococcus spp. causing acute clinical mastitis and their pattern of antibiotic resistance in dairy cows. Materials and methods: Milk was sampled from 128 dairy cows with 191 infected quarters during the period from August 2017 to December 2018. Bacterial species were isolated from the milk samples and identified based on colony morphology and biochemical tests. Multiplex PCR was done for confirmatory detection of the Streptococcus spp. isolates. Results: The chief isolation percentages, from the sampled milk, were Escherichia coli (26%), then Staphylococcus aureus (23%), and Streptococcus dysagalactiae (23%), then Streptococcus agalac¬tiae (20.1%), and finally coagulase-negative Staphylococci (7.7%). In confirmed PCR streptococci isolates, the antibiotic resistance genes have been detected, including macrolides antibiotic resis¬tance genes (ermB and mefA genes), lincosamides antibiotic resistance genes (linB gene), and tetra¬cycline resistance genes (tetM and tetO genes). Age, parity number, cleaning of bedding materials, cleaning of milking facilities, and utensils and udder cleaning practice were significant risk factors for multidrug-resistant streptococcal mastitis in dairy cows. Conclusion: The results of this study explored the phenotypic and genotypic traits of Streptococcus spp. which constitute a usual cause of acute clinical mastitis in dairy cows. The ermB, mefA, tetM, and tetO antibiotic-resistant genes were identified in streptococci isolates from dairy cows milk with acute clinical mastitis, indicating a public health hazard. Thus, veterinary clinical breakpoints are needed to improve surveillance data, improve the hygiene regimen on the farms, and pro¬mote the wise use of antimicrobials. [J Adv Vet Anim Res 2020; 7(2.000): 186-197]

The concentrations and distributions of five sulfonamide, three tetracycline, and two macrolide antibiotics in leachates from three landfill sites in northern Zhejiang Province, China, were determined by solid-phase extraction and ultra-high performance liquid chromatography mass spectrometry. Most of the antibiotics were detected in the leachate samples. The concentrations and distributions of the antibiotics in leachates of different ages were very different. The total sulfonamide, tetracycline, and macrolide concentrations in the leachates ranged from not detected to 1.57 × 103, not detected to 5.19 × 103, and 7.30 to 5.42 × 102 ng/L, respectively. The total concentrations of detectable antibiotics were higher in fresh leachates than aged and middle-aged leachates. Higher TC-group concentrations were found in the leachates than have been found in previously published studies of landfill leachates in China. The results improve our understanding of and ability to manage antibiotic residues in landfills.

Since the first cases of coronavirus disease (COVID-19) have been identified, the search for effective drugs for its treatment has not stopped. The most promising in the treatment of COVID-19 are antimalarial, antiretroviral drugs and macrolide antibiotics. A common side effect for these groups of drugs is their ability to prolong the QT interval and induce paroxysms of polymorphic ventricular tachycardia torsades de pointes, especially in patients with genetic defects of ventricular myocardial repolarization. This article provides management algorithms of COVID-19 in patients with QT interval prolongation and risk of life-threatening ventricular arrhythmias, developed with the support of the EurAsian Arrhythmology Association (EURA-3).

Background Group B Streptococcus (GBS) comprises the normal flora of the female urogenital tract and can be transferred to neonates during delivery, causing invasive diseases. This study was performed to investigate the colonization rate, antibiotic susceptibility, and serotype of GBS among Saudi pregnant women. Materials and methods In this cross-sectional study, vagino-rectal swabs from 400 pregnant women were collected over a period of one year. Identification of GBS isolates and determination of their antibiotic susceptibility were performed using the Microscan Walk Away system. The isolates were then typed using both latex agglutination and capsular gene-based multiplex polymerase chain reaction assays. Results Sixty (15.0%) subjects were colonized by GBS, with serotype Ia as the dominant type (30.0%) followed by serotype III and V (25.0%, each). Only 43 (71.7%) isolates were typed by latex agglutination, whereas the remaining isolates were not typable or were non-specifically typed as compared to the genotyping assay, which revealed the specific type of each GBS isolate. The highest resistance rates were observed for erythromycin and clindamycin (16.7%, each), which were mainly restricted to the prevalent serotypes. Conclusion This study is the first to report the distribution of GBS serotypes based on molecular genotyping in Saudi Arabia. GBS colonization was evident among pregnant women, and resistance to erythromycin and clindamycin was predominant among serotypes Ia, III, and V. Molecular genotyping using capsular gene-based multiplex PCR provided reliable typing of the investigated GBS isolates in terms of sensitivity and specificity as compared to conventional serotyping using latex agglutination.

In recent years, infection with Shewanella putrefaciens has emerged as a serious problem in freshwater aquaculture. In the present study, we report large‐scale mortality in farmed tilapia Oreochromis niloticus from Hisar, North India. The diseased tilapia exhibited lethargy, swimming near the water surface, fin rot, hemorrhages on the operculum, and approximately 40% mortality. Gram‐negative, motile, catalase, and oxidase‐positive bacilli were isolated from the kidney of affected tilapia and confirmed as S. putrefaciens on the basis of biochemical tests and 16S rRNA gene sequencing. The antimicrobial sensitivity test revealed that S. putrefaciens strains were sensitive to quinolone, nitrofuran, tetracycline, aminoglycoside, cephalosporin, aminocyclitol, sulphonamide, and macrolide antibiotics, but resistant to beta‐lactam and glycopeptide antibiotics. The histopathological examination revealed degenerative changes in the kidney, liver, spleen, and intestine suggesting systemic infection. In experimental infection studies, the disease was reproduced in naive tilapia, and the clinical signs resembled those observed in natural cases. Further more, S. putrefaciens was re‐isolated from the kidney of challenged tilapia, fulfilling Koch's postulates. Therefore, the mortality in tilapia was attributed to S. putrefaciens infection.

Penelitian ini bertujuan untuk mengetahui pengaruh pemberian kombinasi antibiotik tylosin tartrate dan fosfomycin sodium yang dicampur dengan air minum terhadap total leukosit dan diferensial leukosit broiler. Penelitian ini menggunakan 24 ekor ayam pedaging/broiler jantan umur 17 hari yang dibagi atas empat perlakuan yaitu diberi kombinasi tylosin tartrate dan fosfomycin sodium 1 g/L air minum (P1), diberi 2 g/L air minum (P2), diberi 3 g/L air minum (P3) dan tanpa diberi tylosin tartrate dan fosfomycin sodium (P0). Perlakuan dilakukan pada ayam broiler umur 17-20 hari dan sampel darah diambil pada umur 21 hari.Darah yang diperoleh ditampung dalam tabung yang berisi antikoagulan ethylene diamine tetra acid (EDTA). Total leukosit dan diferensial leukosit dihitung menggunakan alat uji otomatis (Automatic Blood Counter). Hasil penelitian menunjukkan bahwa total leukosit kelompok P0(44,74± 11,49 x 103 µl) dan P1(46,77± 6,89 x 103 µl) lebih tinggi dibandingkan dengan kelompok P3(35,34± 2,41 x 103 µl), diferensial leukosit menunjukkan bahwa penambahan kombinasi antibiotik tidak berpengaruh nyata terhadap jumlah heterofil, limfosit, dan monosit. Akan tetapi berpengaruh nyata meningkatkan jumlah eosinofil dan basofil. Pemberian kombinasi antibiotik tylosin tartrate dan fosfomycin sodiumyang dicampur dengan air minum dapat meningkatkan jumlah eosinofil dan basofil pada ayam broiler.

Significance The bactericidal activity of macrolide antibiotics correlates with the presence of an extended alkyl-aryl side chain, which accounts for their slow departure rate from the ribosome. Here, we found that the base pair between 23S ribosomal RNA (rRNA) nucleotides 752 and 2609 located in the macrolide binding site is important for the ribosome functionality and for establishing the unique interactions with the extended side chain of macrolide antibiotics. Disruption of the 752-2609 base pair accelerates the departure of extended macrolides from the ribosome and reduces their cidality. Our results demonstrate that not only the chemical features of the antibiotic, but also the structure of the target site contribute to the ability of the inhibitor to kill bacteria., While most of the ribosome-targeting antibiotics are bacteriostatic, some members of the macrolide class demonstrate considerable bactericidal activity. We previously showed that an extended alkyl-aryl side chain is the key structural element determining the macrolides’ slow dissociation from the ribosome and likely accounts for the antibiotics’ cidality. In the nontranslating Escherichia coli ribosome, the extended side chain of macrolides interacts with 23S ribosomal RNA (rRNA) nucleotides A752 and U2609, that were proposed to form a base pair. However, the existence of this base pair in the translating ribosome, its possible functional role, and its impact on the binding and cidality of the antibiotic remain unknown. By engineering E. coli cells carrying individual and compensatory mutations at the 752 and 2609 rRNA positions, we show that integrity of the base pair helps to modulate the ribosomal response to regulatory nascent peptides, determines the slow dissociation rate of the extended macrolides from the ribosome, and increases their bactericidal effect. Our findings demonstrate that the ability of antibiotics to kill bacterial cells relies not only on the chemical nature of the inhibitor, but also on structural features of the target.

Background and Aim: Salmonella spp. are an important group of pathogens responsible for human and animal diseases. This study aimed to estimate the prevalence and identify and characterize of Salmonella spp. isolated from broiler farms of Gazipur, Tangail, and Dhaka districts of Bangladesh. This study also evaluated the difference of Salmonella positivity status between two groups of farms, good practices adapted in broiler rearing at the project intervened farms, and non-project intervened traditional farms. Materials and Methods: A total of 352 samples including 128 cloacal swabs, 32 whole carcasses, 64 feed, 64 water, and 64 attendants' hand rinses were collected through convenient sampling technique from 16 poultry food safety project of Food and Agricultural Organization of United Nations Bangladesh intervened farms and other 16 non-project intervened farms in the same location. Various cultural based techniques and biochemical methods were employed for the estimation of prevalence, isolation, and identification of Salmonella spp. which was further evaluated by polymerase chain reaction. Antimicrobial susceptibility test using disk diffusion methods and serogrouping by slide agglutination test was accomplished for additional characterization. Results: Among the samples, an overall prevalence of Salmonella spp. was 31.25% (110/352) (95% confidence interval [CI]=26.44-36.38%). However, the prevalence of Salmonella spp. was 24.43% (43/176) (95% CI=18.28-31.47) in project intervened farms and 38.07% (67/176) (95% CI=30.87-45.68%) in non-intervened farms. Among the 110 isolates, 31.82% (35/110) were fitted under serogroup B, and the rest of the isolates 75 (68.18%) under serogroup D. Of 110 isolates, 82.72%, 77.27%, 81.82%, and 79.09% were susceptible to ciprofloxacin, gentamycin, norfloxacin, and streptomycin, respectively. In addition, 81.82% and 80% isolates were resistant to erythromycin and tetracycline, respectively. Isolated Salmonella spp. presented moderate resistance to both amoxicillin and azithromycin. Alarmingly, 80.91% (89/110) isolates were shown to be multidrug-resistant Salmonella spp. Conclusion: The study has presented a significant variation of the prevalence of Salmonella spp. between project intervened and non-project intervened farms, and this indicates project intervened farms are comparatively safer than the non-intervened farms considering public health and food safety grounds. This research outcome also has highlighted a substantial proportion of poultry origin multidrug resistance Salmonella spp. is a potential source of public health hazards. In this regard, proper awareness creation and motivational activities on good agriculture practices in poultry rearing and maintaining good personal hygiene at the farmers' level are warranted through participatory training.

We report the application of VCD spectroscopy for the characterization of clarithromycin and erythromycin. We show that the VCD spectra of these large macrolides are distinctly different and that spectra calculations reproduce the experimentally observed VCD signatures. In addition, computed VCD spectra of different epimers indicate that they should also be distinguishable from the correct structure of clarithromycin.

Methicillin resistant Staphylococcus aureus strains pose a serious treatment problem because of their multi-drug resistance (MDR). In staphylococcal strains, resistance to macrolides, lincosamides, and streptogramin B (MLSB) correlates with resistance to methicillin. The rapid transmission of erm genes responsible for MLSB resistance has strongly limited the clinical application of traditional macrolides such as erythromycin. On the other hand, in the age of increasing insensitivity to antibiotics the idea of implementing a therapy based on older generation drugs brings hope that the spread of antibiotic resistance will be limited. A thorough understanding of the resistance mechanisms contributes to design of antibiotics that avoid bacterial insensitivity. This review highlights the mechanisms of action of macrolides and mechanism of resistance to these antibiotics among Staphylococcus aureus.

When antibiotics are given to nursing women, clarithromycin (CLA), roxithromycin (ROK), erythromycin (ERI), azithromycin (AZI), dirithromycin (DIR), and oleandomycin (OLE) are excreted in breast milk. A rapid group-specific antibody test for these analytes in breast milk has been developed as a self-monitoring tool for safe feeding in infants.

Lakes in arid northwestern China, as the main pollutant-holding water bodies in the typical ecologically fragile areas, are facing the unknown risk of exposure to antibiotics and antibiotic resistance genes (ARGs). In this study, five ARGs and one mobile genetic element (intI1) and their relation with antibiotics, microbial communities and water quality were investigated in Ebinur Lake Basin, a typical salt-lake of China. Quantitative PCR analysis indicated that ARGs decreasing order in both surface water and sediment was sul1 >sul2 >tetW>ermB>qnrS, which means sulfonamide resistance genes were the main pollution ARGs. Macrolide antibiotics were the predominant antibiotics in the surface water and sediment in winter, while sulfonamides and quinolones accounted for a high proportion in summer. There was a non-corresponding relationship between ARGs and antibiotics. Moreover, the relationship between ARGs and microbial communities were defined. Sulfonamide resistance genes were carried by a greater diversity of potential host bacteria (76 genera) than other ARGs (9 genera). And their positive correlation with intI1 (p

Macrolide antibiotics are well known for their antibacterial properties, but extensive research in the context of inflammatory lung disease has revealed that they also have powerful immunomodulatory properties. It has been demonstrated that these drugs are therapeutically beneficial in various lung diseases, with evidence they significantly reduce exacerbations in patients with COPD, asthma, bronchiectasis and cystic fibrosis. The efficacy demonstrated in patients infected with macrolide tolerant organisms such as Pseudomonas aeruginosa supports the concept that their efficacy is at least partly related to immunomodulatory rather than antibacterial effects. Inconsistent data and an incomplete understanding of their mechanisms of action hampers the use of macrolide antibiotics as immunomodulatory therapies. Macrolides recently demonstrated no clinically relevant immunomodulatory effects in the context of COVID-19 infection. This review provides an overview of macrolide antibiotics and discusses their immunomodulatory effects and mechanisms of action in the context of inflammatory lung disease.

Infections with Pseudomonas aeruginosa isolates producing Metallo- β- Lactamase (MBL) is a serious worldwide infections. It is associated with, higher mortality rates, more severe disease implicated and with a higher incidence of invasive disease than infections with the bacterial isolate of MBL-nonproducers. This bacteria disseminated in many countries worldwide, with no reports available about their presence in Iraq. The present study was conducted to investigate the changes and the intensity of antibiotics resistance pattern of pediatric urinary tract infection (UTI) in duration of 2 years as well as reporting the first emergence of Metallo- β- Lactamase producing P aerugenosa in Iraq. Standard methods used for isolation and identification of bacteria. Carbapenem- resistance P. aeruginosa UTI isolates were tested for the presence of metallo-β-lactamases productino. This is the first report of the presence of Metallo-β-Lactamase producing P aerugenosa in Iraq region. The results showed no differences in resistance pattern among Gram positive bacteria isolated. While, their was a dramatic increase of Escherichia coli resistance which showed high sensitivity rate to cefotaxim (72.4%), recording an increasing rate of resistance by 12% during 2 years. Klebsiellae pneumoniae resistance profile were increased dramatically during 2 years to trimethoprim and cefotaxim to reach 30 % and 11% respectively, when compaired with our previous study. Regarding P. aeroginosae, there was further increase in resistance toward azithromycin, gentamicin and oxacillin by recording 14%, 11.6% and 11.6% of resistance rates respectively. The striking results of the present study was to find the resistant bacterial isolates of P. aeruginosae toward imipineme. Precisely, 4 (31.8%) out of 13 UTI isolates was found to be resistant to imipineme. In conclusion their was an different increasing resistance rates of isolates toward antibiotics, also an emergence of new MBL producing P. eaurogenosa.

Background: Mycoplasma pneumoniae (MP) is a common cause of lower respiratory tract infection (LRTI) in children between 5 and 15 years of age. The clinical and laboratory findings are usually non-specific and extrapulmonary manifestations can be devastating. Objectives: The objectives of the study were to study the occurrence, clinical features, and laboratory profile of MP infection in children presenting with LRTI to a tertiary care hospital. Materials and Methods: This was a hospital-based prospective study done in the inpatient department of pediatrics of a tertiary care teaching hospital in South India from November 2014 to April 2016. Children aged 1 month–18 years, admitted with LRTI were included in the study. A pre-tested semi-structured questionnaire was used to collect history. MP infection was confirmed using mycoplasma immunoglobulin M enzyme-linked immunosorbent assay. Clinical and laboratory findings were compared between mycoplasma positive and negative groups. Results: Among a total of 268 children with LRTI, MP infection was diagnosed in 41 children (15.3%). The peak occurrence was in 9–12 years (30%) followed by 6–9 years (25.4%) and 3–6 years (21.7%) age group. MP infection was more common among malnourished (29.4%) than well-nourished children (13.1%). None of the clinical and laboratory parameters were specific for the infection. Extrapulmonary manifestations were not seen in our study. Conclusion: MP infection can occur even in children in 3–6 years age group. The clinical and laboratory findings in MP infection are non-specific necessitating empirical treatment with macrolide antibiotics in children more than 3 years of age. It is more common among malnourished children and extrapulmonary manifestations are rare in our population.

Macrolide resistance of staphylococci has risen dramatically in recent years generating a real challenge for their treatment as therapeutic options have become very limited. In this study, an antibiogram analysis of one hundred and fifty Staphylococcus sp. isolates collected from various clinical specimens, against erythromycin, azithromycin, spiramycin, and clindamycin was carried out. Out of the 150 collected Staphylococcus sp. isolates, 54 isolates (36%) showed resistance to two or more of the tested macrolides. Inducible macrolide, lincosamides and streptogramin type B resistance phenotype (iMLS) using D-test was identified in 15 of the resistant isolates (27.8%). Molecular detection of major genes coding for macrolide resistance, including erythromycin ribosomal methylase (ermA and ermC), and macrolide-streptogramin resistance gene (msrA) was carried out using PCR. It was found that 51.8, 37.1 and 11.1% of the resistant isolates carried one, two and three types of the resistance genes, respectively. However, ermC was the most frequently occurring gene (81.5%), followed by the msrA gene (42.6%), then the ermA gene (35.2%). In conclusion, the genotypic analysis revealed that the majority of the tested isolates harbored two or more macrolide resistance-coding genes where 36% displayed resistance to at least two of the most common macrolide antibiotics used in the treatment of such important pathogens particularly in patients exhibiting hypersensitivity to penicillins according to several international guidelines. Therefore, it is crucial to carry out more epidemiologic studies to clearly understand the problem of increasing macrolide resistance among Staphylococci and to implement new guidelines for the treatment of such important pathogens, particularly in Egypt.

Previous studies showed potential benefits of macrolide combined with β-lactam for severe community-acquired pneumonia (CAP). However, it remains inconclusive whether macrolide plus β-lactam is superior to respiratory fluoroquinolone plus β-lactam for patients with severe CAP. Using a nationwide inpatient database in Japan, we performed propensity score matching and inverse probability of treatment weighting (IPTW) to compare 28-day mortality and in-hospital mortality between azithromycin plus β-lactam and levofloxacin plus β-lactam for severe CAP patients admitted to hospital between July 2010 and March 2015. We identified 1,999 patients with severe pneumonia who received azithromycin plus β-lactam (n = 840) or levofloxacin plus β-lactam (n = 1,159) within 2 days after admission. Five-hundred sixty propensity score-matched pairs showed no significant differences between azithromycin plus β-lactam and levofloxacin plus β-lactam in 28-day mortality and in-hospital mortality (19.3% vs. 20.7%, p = 0.601 and 24.8% vs. 26.8%, p = 0.495, respectively). IPTW analysis also showed no significant differences between azithromycin plus β-lactam and levofloxacin plus β-lactam in 28-day mortality (risk difference, −3.5% [95% confidence interval, −8.8% to 1.7%] and in-hospital mortality (risk difference, −3.6%; 95% confidence interval, −9.4% to 2.1%). In conclusion, there were no significant differences in 28-day mortality and in-hospital mortality between azithromycin plus β-lactam and levofloxacin plus β-lactam for severe CAP patients.

Resume Les infections a Legionella sont causees par une bacterie intracellulaire habitant principalement les environnements aquatiques. La contamination se fait par inhalation d’aerosols. Les facteurs de risques principaux sont le tabac, l’immunodepression et l’âge avance. Les signes extra-respiratoires sont peu specifiques. L’argument clinique le plus solide en faveur d’une legionellose est la resistance aux beta lactamines en cas de pneumopathie. Le diagnostic repose avant tout sur l’antigenurie en cas d’infection a Legionella pneumophila de type 1. L’antigenurie est prise en defaut chez les patients infectes a Legionella non pneumophilia comme les patients immunodeprimes. La culture et la PCR sont alors indispensables au diagnostic. La maladie des legionnaires, forme pulmonaire de l’infection a Legionella, est grave, en particulier chez les sujets âges et/ou les patients immunodeprimes. Le taux de mortalite varie de 10 % dans la population generale, a 50 % en cas d’hospitalisation en reanimation. Le traitement repose sur les macrolides ou les fluoroquinolones. La resistance aux antibiotiques est exceptionnelle.

The article describes state-of-the-art knowledge regarding etiology, epidemiology, clinical features and diagnostic criteria for respiratory infections caused byMycoplasma pneumoniae(M. pneumoniae). It presents the characteristics of the main forms of lesions in mycoplasma infections of the respiratory tract – pharyngitis, bronchitis and pneumonia. Particular attention is paid to the differential diagnosis of community-acquired pneumonia of pneumococcal and mycoplasma etiology. The issues of rational choice of initial etiotropic therapy for the treatment of respiratory mycoplasmosis in children are discussed.

Macrolides are widely prescribed in clinic to treat various respiratory tract infections. However, due to their inappropriate use, the prevalence of macrolide-resistant strains among clinical isolates has become a concern for public health. Therefore, novel macrolides skeleton structures against resistant pathogens are badly needed. Thus, three series of novel 15-membered 11a-azahomoclarithromycin derivatives (series A-C) with the 1, 2, 3-triazole side chain were designed and synthesized through creatively opening the ring of clarithromycin (CAM), expanding the ring properly and introducing a suitable side chain of 1, 2, 3-triazole at the C12 and C13 positions, and evaluated for their antibacterial activity. The antibacterial results indicated that compounds 38b, 38l and 38v possessed strong antibacterial activity against Staphylococcus aureus ATCC25923 (0.25 μg/mL) and Bacillus subtilis ATCC9372 (0.25 μg/mL). Furthermore, compounds 9e and 38g were found to exhibit promising potent activity (8 μg/mL) against Streptococcus pneumonia AB11 expressing the ermB and mefA genes. In addition, the determination of minimum bactericidal concentration (MBC) indicated that the most promising compounds 38b, 38l, 38v, 9e and 38g were excellent bacteriostatic agents. The bactericidal curve showed that 9e exhibited antibacterial activity through bacteriostatic mechanism. Finally, 38b, 38l and 38v were confirmed to be non-toxic to MCF-7 breast cancer cells up to a concentration of 32 μg/mL in preliminary cytotoxicity assay. In summary, 38b, 38l, 38v, 9e and 38g can be served as lead compounds to provide a new perspective for further structural optimization.