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Статті в журналах з теми "Macroline"

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Автор: Grafiati

Опубліковано: 6 вересня 2023

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1

Lim, Siew-Huah, Shin-Jowl Tan, Yun-Yee Low, and Toh-Seok Kam. "Lumutinines A–D, Linearly Fused Macroline–Macroline and Macroline–Sarpagine Bisindoles fromAlstonia macrophylla." Journal of Natural Products 74, no. 12 (December 27, 2011): 2556–62. http://dx.doi.org/10.1021/np200730j.

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2

Lim, Siew-Huah, Yun-Yee Low, G. Subramaniam, Zanariah Abdullah, Noel F. Thomas, and Toh-Seok Kam. "Lumusidines A−D and villalstonidine F, macroline–macroline and macroline–pleiocarpamine bisindole alkaloids from Alstonia macrophylla." Phytochemistry 87 (March 2013): 148–56. http://dx.doi.org/10.1016/j.phytochem.2012.11.005.

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3

Tan, Shin-Jowl, Kuan-Hon Lim, G. Subramaniam, and Toh-Seok Kam. "Macroline–sarpagine and macroline–pleiocarpamine bisindole alkaloids from Alstonia angustifolia." Phytochemistry 85 (January 2013): 194–202. http://dx.doi.org/10.1016/j.phytochem.2012.08.016.

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4

Lim, Siew-Huah, Yun-Yee Low, Shin-Jowl Tan, Kuan-Hon Lim, Noel F. Thomas, and Toh-Seok Kam. "Perhentidines A–C: Macroline–Macroline Bisindoles fromAlstoniaand the Absolute Configuration of Perhentinine and Macralstonine." Journal of Natural Products 75, no. 5 (May 4, 2012): 942–50. http://dx.doi.org/10.1021/np300120p.

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5

Bi, Yingzhi, and James M. Cook. "General approach for the synthesis of macroline/sarpagine alkaloids. The total synthesis of (+)-macroline." Tetrahedron Letters 34, no. 28 (July 1993): 4501–4. http://dx.doi.org/10.1016/0040-4039(93)88069-u.

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6

Zhang, Ye, Lei Zhang, and Xiangbing Qi. "Total Synthesis of (–)-Alstofolinine A: Selected Furan Oxidation/ Cyclization Cascade." Synlett 31, no. 01 (November 5, 2019): 7–12. http://dx.doi.org/10.1055/s-0039-1690247.

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Анотація:

Indole-fused tetracyclic ring systems containing nitrogen atoms are common core skeletons of many indole alkaloids such as sarpagine, macroline, and ajmaline. Efficient and stereoselective construction of these ring systems can promote the development of the corresponding alkaloid syntheses. In this article, we briefly summarize our current progress toward the application of the aza-Achmatowicz reaction and indole nucleophilic addition reaction cascade for the first asymmetric total synthesis of the macroline-type indole alkaloid (–)-Alstofolinine A. Our synthetic strategy is based on furan oxidation/rearrangement and proceeds from easily accessible materials such as indole and furan derivatives.

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7

Kadam, Vilas D., Sridhara Shanmukha Rao B., S. K. Mahesh, Mithun Chakraborty, S. Phani Babu Vemulapalli, Satya Narayana Dayaka, and Gangarajula Sudhakar. "Stereoselective Access to the Core Structure of Macroline-Type Indole Alkaloids: Total Synthesis of Macroline and Alstomicine." Organic Letters 20, no. 16 (August 2018): 4782–86. http://dx.doi.org/10.1021/acs.orglett.8b01921.

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8

Rahman, Md Toufiqur, Veera Venkata Naga Phani Babu Tiruveedhula, Michael Rajesh Stephen, Sundari K. Rallapalli, Kamal P. Pandey та James M. Cook. "Completion of the Total Synthesis of Several Bioactive Sarpagine/Macroline Alkaloids including the Important NF-κB Inhibitor N4-Methyltalpinine". Molecules 27, № 5 (7 березня 2022): 1738. http://dx.doi.org/10.3390/molecules27051738.

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The unification of the general synthetic strategy regarding the important and emerging group of C-19 methyl-substituted sarpagine/macroline alkaloids has culminated in the completion of the total synthesis of several bioactive alkaloids. Key transformations include an ACE-Cl mediated late-stage N(4)-demethylation and an anhydrous acid-mediated intramolecular quaternary hemiaminal formation between a tertiary amine and an aldehyde function to allow efficient access to several biologically important alkaloids from this group. Herein, the enantiospecific total synthesis of the first known sarpagine/macroline alkaloid with NF-κB inhibitory activity, N(4)-methyltalpinine (as a chloride salt), as well as the anticancer alkaloids talpinine, O-acetyltalpinine, and macrocarpines F–G, are described.

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9

Kam, Toh-Seok, and Yeun-Mun Choo. "Novel Macroline Oxindoles from a Malayan Alstonia." Tetrahedron 56, no. 33 (August 2000): 6143–50. http://dx.doi.org/10.1016/s0040-4020(00)00564-0.

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10

Lim, Siew-Huah, Yun-Yee Low, Saravana Kumar Sinniah, Kien-Thai Yong, Kae-Shin Sim, and Toh-Seok Kam. "Macroline, akuammiline, sarpagine, and ajmaline alkaloids from Alstonia macrophylla." Phytochemistry 98 (February 2014): 204–15. http://dx.doi.org/10.1016/j.phytochem.2013.11.014.

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11

Yeap, Joanne Soon-Yee, Suerialoasan Navanesan, Kae-Shin Sim, Kien-Thai Yong, Subramaniam Gurusamy, Siew-Huah Lim, Yun-Yee Low, and Toh-Seok Kam. "Ajmaline, Oxindole, and Cytotoxic Macroline–Akuammiline Bisindole Alkaloids fromAlstonia penangiana." Journal of Natural Products 81, no. 5 (May 10, 2018): 1266–77. http://dx.doi.org/10.1021/acs.jnatprod.8b00170.

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12

Yeap, Joanne Soon-Yee, Hazwani Mat Saad, Chun-Hoe Tan, Kae-Shin Sim, Siew-Huah Lim, Yun-Yee Low, and Toh-Seok Kam. "Macroline–Sarpagine Bisindole Alkaloids with Antiproliferative Activity from Alstonia penangiana." Journal of Natural Products 82, no. 11 (October 23, 2019): 3121–32. http://dx.doi.org/10.1021/acs.jnatprod.9b00712.

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13

Tan, Shin-Jowl, Jun-Lee Lim, Yun-Yee Low, Kae-Shin Sim, Siew-Huah Lim, and Toh-Seok Kam. "Oxidized Derivatives of Macroline, Sarpagine, and Pleiocarpamine Alkaloids fromAlstonia angustifolia." Journal of Natural Products 77, no. 9 (September 11, 2014): 2068–80. http://dx.doi.org/10.1021/np500439u.

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14

Edwankar, Chitra R., Rahul V. Edwankar, Sundari Rallapalli, and James M. Cook. "General Approach to the Total Synthesis of Macroline-Related Sarpagine and Ajmaline Alkaloids1." Natural Product Communications 3, no. 11 (November 2008): 1934578X0800301. http://dx.doi.org/10.1177/1934578x0800301114.

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Анотація:

Described in this review is a general and efficient strategy for the synthesis of macroline-related sarpagine and ajmaline alkaloids. The tetracyclic ketone in the parent system, as well as the alkoxy substituted series served as templates for the synthesis of these complex molecules. The palladium-mediated enolate cross coupling process, regiospecific hydroboration, and Tollens reaction are some of the key transformations that have been employed for further functionalization of these templates. Synthetic routes that have been improved, in order to obtain gram quantities of these alkaloids form a part of this review.

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15

Liu, Xiaoxiang, Chunchun Zhang, Xuebin Liao, and James M. Cook. "Enantiospecific total synthesis of the enantiomer of the indole alkaloid intermediate macroline." Tetrahedron Letters 43, no. 41 (October 2002): 7373–77. http://dx.doi.org/10.1016/s0040-4039(02)01729-x.

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16

Kam, Toh-Seok, Yeun-Mun Choo, and Kanki Komiyama. "Unusual spirocyclic macroline alkaloids, nitrogenous derivatives, and a cytotoxic bisindole from Alstonia." Tetrahedron 60, no. 18 (April 2004): 3957–66. http://dx.doi.org/10.1016/j.tet.2004.03.031.

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17

Čipčić Paljetak, Hana, Donatella Verbanac, Jasna Padovan, Miroslava Dominis-Kramarić, Željko Kelnerić, Mihaela Perić, Mihailo Banjanac, et al. "Macrolones Are a Novel Class of Macrolide Antibiotics Active against Key Resistant Respiratory PathogensIn VitroandIn Vivo." Antimicrobial Agents and Chemotherapy 60, no. 9 (June 27, 2016): 5337–48. http://dx.doi.org/10.1128/aac.00524-16.

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ABSTRACTAs we face an alarming increase in bacterial resistance to current antibacterial chemotherapeutics, expanding the available therapeutic arsenal in the fight against resistant bacterial pathogens causing respiratory tract infections is of high importance. The antibacterial potency of macrolones, a novel class of macrolide antibiotics, against key respiratory pathogens was evaluatedin vitroandin vivo. MIC values againstStreptococcus pneumoniae,Streptococcus pyogenes,Staphylococcus aureus, andHaemophilus influenzaestrains sensitive to macrolide antibiotics and with defined macrolide resistance mechanisms were determined. The propensity of macrolones to induce the expression of inducibleermgenes was tested by the triple-disk method and incubation in the presence of subinhibitory concentrations of compounds.In vivoefficacy was assessed in a murine model ofS. pneumoniae-induced pneumonia, and pharmacokinetic (PK) profiles in mice were determined. Thein vitroantibacterial profiles of macrolones were superior to those of marketed macrolide antibiotics, including the ketolide telithromycin, and the compounds did not induce the expression of inducibleermgenes. They acted as typical protein synthesis inhibitors in anEscherichia colitranscription/translation assay. Macrolones were characterized by low to moderate systemic clearance, a large volume of distribution, a long half-life, and low oral bioavailability. They were highly efficacious in a murine model of pneumonia after intraperitoneal application even against anS. pneumoniaestrain with constitutive resistance to macrolide-lincosamide-streptogramin B antibiotics. Macrolones are the class of macrolide antibiotics with an outstanding antibacterial profile and reasonable PK parameters resulting in goodin vivoefficacy.

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18

Lewis, Simon E. "Recent advances in the chemistry of macroline, sarpagine and ajmaline-related indole alkaloids." Tetrahedron 62, no. 37 (September 2006): 8655–81. http://dx.doi.org/10.1016/j.tet.2006.06.017.

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19

Bergman, Miika, Solja Huikko, Pentti Huovinen, Pirkko Paakkari, and Helena Seppälä. "Macrolide and Azithromycin Use Are Linked to Increased Macrolide Resistance in Streptococcus pneumoniae." Antimicrobial Agents and Chemotherapy 50, no. 11 (August 28, 2006): 3646–50. http://dx.doi.org/10.1128/aac.00234-06.

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ABSTRACT The connection between regional rates of antimicrobial resistance in Streptococcus pneumoniae and regional antimicrobial use in Finland was investigated. During the 6-year study period of 1997 to 2002, a total of 31,609 S. pneumoniae isolates were tested for penicillin resistance and a total of 23,769 isolates were tested for macrolide resistance in 18 central hospital districts in Finland. The regional macrolide resistance rates were compared with the local use of (i) all macrolides pooled and (ii) azithromycin. The penicillin resistance levels were compared with the consumption data for (i) penicillins, (ii) cephalosporins, (iii) all beta-lactams pooled, and (iv) all macrolides pooled. A statistically significant association between macrolide resistance and total use of macrolides and the use of azithromycin was found. Moreover, total use of beta-lactams and total use of cephalosporins were significantly connected to low-level penicillin resistance. A statistically significant association between penicillin-nonsusceptible isolates and penicillin or total macrolide consumption was not found. In conclusion, total macrolide use and azithromycin use are associated with increased macrolide resistance, and beta-lactam use and cephalosporin use are connected to increased low-level penicillin resistance in S. pneumoniae. Unnecessary prescribing of macrolides and cephalosporins should be avoided.

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20

Shaeer, Kristy M., Elias B. Chahine, Sheeba Varghese Gupta, and Jonathan C. Cho. "Macrolide Allergic Reactions." Pharmacy 7, no. 3 (September 18, 2019): 135. http://dx.doi.org/10.3390/pharmacy7030135.

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Macrolides are antimicrobial agents that can be used to treat a variety of infections. Allergic reactions to macrolides occur infrequently but can include minor to severe cutaneous reactions as well as systemic life-threatening reactions such as anaphylaxis. Most reports of allergic reactions occurred in patients without prior exposure to a macrolide. Cross-reactivity among macrolides may occur due to the similarities in their chemical structures; however, some published literature indicates that some patients can tolerate a different macrolide. Most published reports detailed an allergic reaction to erythromycin. Desensitization protocols to clarithromycin and azithromycin have been described in the literature. The purpose of this article is to summarize macrolide-associated allergic reactions reported in published literature. An extensive literature search was conducted to identify publications linking macrolides to hypersensitivity reactions.

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21

Chancey, Scott T., Xiaoliu Zhou, Dorothea Zähner, and David S. Stephens. "Induction of Efflux-Mediated Macrolide Resistance in Streptococcus pneumoniae." Antimicrobial Agents and Chemotherapy 55, no. 7 (May 2, 2011): 3413–22. http://dx.doi.org/10.1128/aac.00060-11.

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ABSTRACTThe antimicrobial efflux system encoded by the operonmef(E)-melon the mobile genetic element MEGA inStreptococcus pneumoniaeand other Gram-positive bacteria is inducible by macrolide antibiotics and antimicrobial peptides. Induction may affect the clinical response to the use of macrolides. We developedmef(E)reporter constructs and a disk diffusion induction and resistance assay to determine the kinetics and basis ofmef(E)-melinduction. Induction occurred rapidly, with a >15-fold increase in transcription within 1 h of exposure to subinhibitory concentrations of erythromycin. A spectrum of environmental conditions, including competence and nonmacrolide antibiotics with distinct cellular targets, did not inducemef(E).Using 16 different structurally defined macrolides, induction was correlated with the amino sugar attached to C-5 of the macrolide lactone ring, not with the size (e.g., 14-, 15- or 16-member) of the ring or with the presence of the neutral sugar cladinose at C-3. Macrolides with a monosaccharide attached to C-5, known to block exit of the nascent peptide from the ribosome after the incorporation of up to eight amino acids, inducedmef(E)expression. Macrolides with a C-5 disaccharide, which extends the macrolide into the ribosomal exit tunnel, disrupting peptidyl transferase activity, did not induce it. The induction ofmef(E)did not require macrolide efflux, but the affinity of macrolides for the ribosome determined the availability for efflux and pneumococcal susceptibility. The induction ofmef(E)-melexpression by inducing macrolides appears to be based on specific interactions of the macrolide C-5 saccharide with the ribosome that alleviate transcriptional attenuation ofmef(E)-mel.

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22

Garza-Ramos, Georgina, Liqun Xiong, Ping Zhong, and Alexander Mankin. "Binding Site of Macrolide Antibiotics on the Ribosome: New Resistance Mutation Identifies a Specific Interaction of Ketolides with rRNA." Journal of Bacteriology 183, no. 23 (December 1, 2001): 6898–907. http://dx.doi.org/10.1128/jb.183.23.6898-6907.2001.

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ABSTRACT Macrolides represent a clinically important class of antibiotics that block protein synthesis by interacting with the large ribosomal subunit. The macrolide binding site is composed primarily of rRNA. However, the mode of interaction of macrolides with rRNA and the exact location of the drug binding site have yet to be described. A new class of macrolide antibiotics, known as ketolides, show improved activity against organisms that have developed resistance to previously used macrolides. The biochemical reasons for increased potency of ketolides remain unknown. Here we describe the first mutation that confers resistance to ketolide antibiotics while leaving cells sensitive to other types of macrolides. A transition of U to C at position 2609 of 23S rRNA rendered E. coli cells resistant to two different types of ketolides, telithromycin and ABT-773, but increased slightly the sensitivity to erythromycin, azithromycin, and a cladinose-containing derivative of telithromycin. Ribosomes isolated from the mutant cells had reduced affinity for ketolides, while their affinity for erythromycin was not diminished. Possible direct interaction of ketolides with position 2609 in 23S rRNA was further confirmed by RNA footprinting. The newly isolated ketolide-resistance mutation, as well as 23S rRNA positions shown previously to be involved in interaction with macrolide antibiotics, have been modeled in the crystallographic structure of the large ribosomal subunit. The location of the macrolide binding site in the nascent peptide exit tunnel at some distance from the peptidyl transferase center agrees with the proposed model of macrolide inhibitory action and explains the dominant nature of macrolide resistance mutations. Spatial separation of the rRNA residues involved in universal contacts with macrolides from those believed to participate in structure-specific interactions with ketolides provides the structural basis for the improved activity of the broader spectrum group of macrolide antibiotics.

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23

Suzuki, Satowa, Tsutomu Yamazaki, Mitsuo Narita, Norio Okazaki, Isao Suzuki, Tomoaki Andoh, Mayumi Matsuoka, Tsuyoshi Kenri, Yoshichika Arakawa, and Tsuguo Sasaki. "Clinical Evaluation of Macrolide-Resistant Mycoplasma pneumoniae." Antimicrobial Agents and Chemotherapy 50, no. 2 (February 2006): 709–12. http://dx.doi.org/10.1128/aac.50.2.709-712.2006.

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ABSTRACT Macrolide-resistant Mycoplasma pneumoniae (MR M. pneumoniae) has been isolated from clinical specimens in Japan since 2000. A comparative study was carried out to determine whether or not macrolides are effective in treating patients infected with MR M. pneumoniae. The clinical courses of 11 patients with MR M. pneumoniae infection (MR patients) treated with macrolides were compared with those of 26 patients with macrolide-susceptible M. pneumoniae infection (MS patients). The total febrile days and the number of febrile days during macrolide administration were longer in the MR patients than in the MS patients (median of 8 days versus median of 5 days [P = 0.019] and 3 days versus 1 day [P = 0.002], respectively). In addition, the MR patients were more likely than the MS patients to have had a change of the initially prescribed macrolide to another antimicrobial agent (63.6% versus 3.8%; odds ratio, 43.8; P < 0.001), which might reflect the pediatrician's judgment that the initially prescribed macrolide was not sufficiently effective in these patients. Despite the fact that the febrile period was prolonged in MR patients given macrolides, the fever resolved even when the initial prescription was not changed. These results show that macrolides are certainly less effective in MR patients.

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24

Lin, Chien-Yu, Tzu-Lin Yeh, Shu-Jung Liu, Hsin-Hui Lin, Yu-Jyun Cheng, Hua-His Hung, Mu-Chieh Tsai, Jui-Ming Liu, and Wei-Te Lei. "Effects of Macrolide Treatment during the Hospitalization of Children with Childhood Wheezing Disease: A Systematic Review and Meta-Analysis." Journal of Clinical Medicine 7, no. 11 (November 9, 2018): 432. http://dx.doi.org/10.3390/jcm7110432.

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Children are susceptible to a variety of respiratory infections. Wheezing is a common sign presented by children with respiratory infections. Asthma, bronchiolitis, and bronchitis are common causes of childhood wheezing disease (CWD) and are regarded as overlapping disease spectra. Macrolides are common antimicrobial agents with anti-inflammatory effects. We conducted a comprehensive literature search and a systematic review of studies that investigated the influences of macrolide treatment on CWD. The primary outcomes were the impact of macrolides on hospitalization courses of patients with CWD. Data pertaining to the study population, macrolide treatment, hospital courses, and recurrences were analyzed. Twenty-three studies with a combined study population of 2210 patients were included in the systematic review. Any kind of benefit from macrolide treatment was observed in approximately two-thirds of the studies (15/23). Eight studies were included in the meta-analysis to investigate the influence of macrolides on the length of stay (LOS), duration of oxygen demand (DOD), symptoms and signs of respiratory distress, and re-admission rates. Although the benefits of macrolide treatment were reported in several of the studies, no significant differences in LOS, DOD, symptoms and signs of respiratory distress, or re-admission rates were observed in patients undergoing macrolide treatment. In conclusion, any kind of benefit of macrolide treatment was observed in approximately two-thirds of the studies; however, no obvious benefits of macrolide treatment were observed in the hospitalization courses of children with CWD. The routine use of macrolides to improve the hospitalization course of children with CWD is not suggested.

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25

Trott, Darren J., John Turnidge, Jessica H. Kovac, Shabbir Simjee, Danny Wilson, and Jeffrey Watts. "Comparative macrolide use in humans and animals: should macrolides be moved off the World Health Organisation’s critically important antimicrobial list?" Journal of Antimicrobial Chemotherapy 76, no. 8 (May 6, 2021): 1955–61. http://dx.doi.org/10.1093/jac/dkab120.

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Macrolide antibiotics are categorized by the WHO as Highest Priority, Critically Important Antimicrobials due to their recommendation as treatment for severe cases of campylobacteriosis in humans; a self-limiting, rarely life-threatening, zoonotic foodborne infection. Low rates of macrolide resistance in Campylobacter jejuni and the availability of alternative treatments have prompted some regulatory schemes to assign macrolides to a lower importance category. Apart from rare, specific infections, macrolides largely play a supportive role to other drug classes in human medicine. By contrast, although the advent of alternative control methods has seen significant reductions in macrolide use in intensive livestock, they still have a crucial role in the treatment/control of respiratory infections and liver abscesses in cattle. Whilst acknowledging that ongoing surveillance is required to reduce the spread of recently emerged, transferable macrolide resistance among Campylobacter, this article recommends that macrolides should be moved to the WHO Highly Important category.

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26

Zhang, L. H., and J. M. Cook. "General approach to the synthesis of macroline-related alkaloids. Stereospecific total synthesis of (-)-alstonerine." Journal of the American Chemical Society 112, no. 10 (May 1990): 4088–90. http://dx.doi.org/10.1021/ja00166a084.

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27

Bi, Yingzhi, Lin-Hua Zhang, Linda K. Hamaker, and James M. Cook. "Enantiospecific Synthesis of (-)-Alstonerine and (+)-Macroline as Well as a Partial Synthesis of (+)-Villalstonine." Journal of the American Chemical Society 116, no. 20 (October 1994): 9027–41. http://dx.doi.org/10.1021/ja00099a021.

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28

Wilk, Wolfram, Andrea Nören-Müller, Markus Kaiser, and Herbert Waldmann. "Biology-Oriented Combined Solid- and Solution-Phase Synthesis of a Macroline-Like Compound Collection." Chemistry - A European Journal 15, no. 44 (November 9, 2009): 11976–84. http://dx.doi.org/10.1002/chem.200901797.

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29

Amábile-Cuevas, Carlos F. "Macrolides at Clinically-Relevant Concentrations May Induce Biofilm Formation in Macrolide-Resistant Staphylococcus aureus." Antibiotics 12, no. 2 (January 17, 2023): 187. http://dx.doi.org/10.3390/antibiotics12020187.

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Анотація:

Macrolides inhibit biofilm formation in several Gram-negative, intrinsically-resistant bacterial species. However, the effect of macrolides upon biofilm formation by susceptible Gram-positive bacteria has been much less explored as such concentrations also inhibit cell growth. To circumvent this problem, the effect of macrolides (erythromycin, clarithromycin and azithromycin) at 0.5–2 µg/mL, upon biofilm formation, was explored on macrolide-resistant Staphylococcus aureus isolates, using the crystal violet assay with 96-well plates. Early (4 h) biofilm formation by strains having constitutive target-modification resistance was consistently induced by all macrolides but not in azithromycin-treated cells in longer (8 and 12 h) incubation. In inducible-resistance isolates, early biofilm formation was enhanced by some macrolide treatments, compared to similar cell growth in the absence of antibiotics; but the typical decay of biofilms at longer incubation appeared prematurely in macrolide-treated cultures. Biofilm formation in an efflux-mediated resistant isolate was not affected by macrolides. These results indicate that macrolides induce the formation of biofilm by resistant S. aureus isolates, especially during the early stages. This suggests that the empirical use of macrolides against infections caused by resistant S. aureus strains could not only result in clinical failure but even in the enhancement of biofilms, making further treatment difficult.

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30

Zhang, Liyun, Xiaoqing Xu, Sara Badawy, Awais Ihsan, Zhenli Liu, Changqing Xie, Xu Wang, and Yanfei Tao. "A Review: Effects of Macrolides on CYP450 Enzymes." Current Drug Metabolism 21, no. 12 (December 30, 2020): 928–37. http://dx.doi.org/10.2174/1389200221666200817113920.

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: As a kind of haemoglobin, cytochrome P450 enzymes (CYP450) participate in the metabolism of many substances, including endogenous substances, exogenous substances and drugs. It is estimated that 60% of common prescription drugs require bioconversion through CYP450. The influence of macrolides on CYP450 contributes to the metabolism and drug-drug interactions (DDIs) of macrolides. At present, most studies on the effects of macrolides on CYP450 are focused on CYP3A, but a few exist on other enzymes and drug combinations, such as telithromycin, which can decrease the activity of hepatic CYP1A2 and CYP3A2. This article summarizes some published applications of the influence of macrolides on CYP450 and the DDIs of macrolides caused by CYP450. And the article may subsequently guide the rational use of drugs in clinical trials. To a certain extent, poisoning caused by adverse drug interactions can be avoided. Unreasonable use of macrolide antibiotics may enable the presence of residue of macrolide antibiotics in animal-origin food. It is unhealthy for people to eat food with macrolide antibiotic residues. So it is of great significance to guarantee food safety and protect the health of consumers by the rational use of macrolides. This review gives a detailed description of the influence of macrolides on CYP450 and the DDIs of macrolides caused by CYP450. Moreover, it offers a perspective for researchers to further explore in this area.

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Skryabina, A. A., V. V. Nikiforov, M. Z. Shakhmardanov, M. S. Zastrozhin та D. A. Sychev. "</title> <original_language_title>Актуальные вопросы патогенетического лечения болезни Фабри в Российской Федерации</original_language_title> </titles> <contributors> <person_name sequence='first' contributor_role='author'> <given_name>S.</given_name> <surname>Moiseev</surname> </person_name> <person_name sequence='first' contributor_role='author'> <given_name>L.M.</given_name> <surname>Kuzenkova</surname> </person_name> <person_name sequence='first' contributor_role='author'> <given_name>N.D.</given_name> <surname>Vashakamadse</surname> </person_name> <person_name sequence='first' contributor_role='author'> <given_name>E.M.</given_name> <surname>Shilov</surname> </person_name> <person_name sequence='first' contributor_role='author'> <given_name>O.N.</given_name> <surname>Kotenko</surname> </person_name> <person_name sequence='first' contributor_role='author'> <given_name>T.V.</given_name> <surname>Podkletnova</surname> </person_name> <person_name sequence='first' contributor_role='author'> <given_name>A.N.</given_name> <surname>Semyachkina</surname> </person_name> <person_name sequence='first' contributor_role='author'> <given_name>M.S.</given_name> <surname>Harlap</surname> </person_name> </contributors> <jats:abstract xml:lang='en'> <jats:p></jats:p> </jats:abstract> <publication_date media_type='online'> <month>12</month> <day>03</day> <year>2022</year> </publication_date> <publication_date media_type='print'> <month>11</month> <day>03</day> <year>2022</year> </publication_date> <pages> <first_page>66</first_page> <last_page>68</last_page> </pages> <doi_data> <doi>10.32756/0869-5490-2022-4-66-68</doi> <resource>https://clinpharm-journal.ru/articles/2022-4/aktualnye-voprosy-patogeneticheskogo-lecheniya-bolezni-fabri-v-rossijskoj-federatsii/</resource> </doi_data> </journal_article>  <journal_article publication_type='full_text'> <titles> <title>Macrolide antibiotics: chemical structure, mechanism of action and safety issues". Clinical pharmacology and therapy 35, № 4 (3 листопада 2022): 71–76. http://dx.doi.org/10.32756/0869-5490-2022-4-71-76.

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The article provides an overview of current publications on the chemical structure, mechanism of action and safety of macrolide antibiotics. We conducted a search in PubMed and Google Scholar databases for the scientific articles published from 2010 to 2021. The following key words were used: macrolides, macrolide antibiotics, erythromycin, clarithromycin, azithromycin, mechanism of action, adverse drug reactions, toxicity. Macrolides are broad-spectrum antibiotics used to treat a wide range of both local and systemic infectious diseases. Macrolides are generally safe, although they can induce certain dose-dependent adverse drug reactions.

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CHEN, QING, WEI LU, DANYING ZHOU, GUOTONG ZHENG, HONGMAO LIU, CHANGRUI QIAN, WANGXIAO ZHOU, et al. "Characterization of Two Macrolide Resistance-Related Genes in Multidrug-Resistant Pseudomonas aeruginosa Isolates." Polish Journal of Microbiology 69, no. 3 (September 8, 2020): 349–56. http://dx.doi.org/10.33073/pjm-2020-038.

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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.

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Lee, Hyunju, Youn Young Choi, Young Joo Sohn, Ye Kyung Kim, Mi Seon Han, Ki Wook Yun, Kyungmin Kim, et al. "Clinical Efficacy of Doxycycline for Treatment of Macrolide-Resistant Mycoplasma pneumoniae Pneumonia in Children." Antibiotics 10, no. 2 (February 17, 2021): 192. http://dx.doi.org/10.3390/antibiotics10020192.

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In areas with high prevalence of macrolide-resistant Mycoplasma pneumoniae (MRMP) pneumonia, treatment in children has become challenging. This study aimed to analyze the efficacy of macrolides and doxycycline with regard to the presence of macrolide resistance. We analyzed children with MP pneumonia during the two recent epidemics of 2014–2015 and 2019–2020 from four hospitals in Korea. Nasopharyngeal samples were obtained from children with pneumonia for MP cultures and polymerase chain reaction (PCR). Macrolide resistance was determined by the analysis of 23S rRNA gene transition. Time to defervescence and to chest X-ray improvement were analyzed. Of 145 cases, the median age was 5.0 years and MRMP accounted for 59 (40.7%). Among macrolide-susceptible MP (MSMP), 78 (90.7%) were treated with macrolides and 21 (35.6%) in the MRMP group with doxycycline. In MRMP pneumonia, shorter days to defervescence (2 vs. 5 days, p < 0.001) and to chest X-ray improvement (3 vs. 6 days, p < 0.001) in the doxycycline group than in the macrolide group was observed, whereas no differences were observed among children with MSMP pneumonia. Compared to macrolides, treatment with doxycycline resulted in better outcomes with a shorter time to defervescence and to chest X-ray improvement among children with MRMP pneumonia.

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Tan, Shin-Jowl, Ward T. Robinson, Kanki Komiyama, and Toh-Seok Kam. "Macrodasines A–G, macroline indole alkaloids incorporating fused spirocyclic tetrahydrofuran–tetrahydrofuran and tetrahydrofuran–tetrahydropyran rings." Tetrahedron 67, no. 21 (May 2011): 3830–38. http://dx.doi.org/10.1016/j.tet.2011.03.099.

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Kam, Toh-Seok, and Yeun-Mun Choo. "Macrodasine A, a novel macroline derivative incorporating fused spirocyclic tetrahydrofuran rings containing a spiroacetal moiety." Tetrahedron Letters 44, no. 49 (December 2003): 8787–89. http://dx.doi.org/10.1016/j.tetlet.2003.09.188.

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Takayama, Hiromitsu, Chada Phisalaphong, Mariko Kitajima, Norio Aimi, and Shin-ichiro Sakai. "An efficient synthetic pathway to the macroline-type indole alkaloids, talcarpine and alstonerine from ajmaline." Tetrahedron 47, no. 8 (January 1991): 1383–92. http://dx.doi.org/10.1016/s0040-4020(01)86414-0.

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Gibreel, Amera, Nicole M. Wetsch, and Diane E. Taylor. "Contribution of the CmeABC Efflux Pump to Macrolide and Tetracycline Resistance in Campylobacter jejuni." Antimicrobial Agents and Chemotherapy 51, no. 9 (July 2, 2007): 3212–16. http://dx.doi.org/10.1128/aac.01592-06.

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ABSTRACT We investigated the involvement of the CmeABC efflux pump in acquired resistance of Campylobacter jejuni to macrolides and tetracycline. Inactivation of the cmeB gene had no effect on macrolide resistance when all copies of the target gene carried an A2074C mutation. In contrast, the CmeABC pump significantly contributed to macrolide resistance when two or three copies of the 23S rRNA had an A2075G transition. Inactivation of the cmeB gene led to restoration of tetracycline susceptibility in the isolates examined. Complete susceptibility to tetracycline or macrolides, however, was not restored when phenylalanine-arginine β-naphthylamide was used. These data confirm contribution of the CmeABC efflux pump to acquired resistance of Campylobacter jejuni to tetracycline and macrolides.

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Chávez, Abelardo Claudio Fernández, Luis García Comas, Luis Manzano Espinosa, Jose Yuste Lobo, Octavio Corral Pazos de Provens, and Jesús María Aranaz Andrés. "Impact of previous macrolide use on invasive pneumococcal disease due to erythromycin-resistant serotypes in adults over 59 years of age." European Journal of Clinical Microbiology & Infectious Diseases 41, no. 2 (October 31, 2021): 227–34. http://dx.doi.org/10.1007/s10096-021-04368-2.

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AbstractThe major goals of the study were to describe the invasive pneumococcal disease (IPD) cases due to erythromycin-resistant serotypes and to evaluate the association between these cases and recent macrolide use in individuals aged over 59 years. We selected cases of IPD reported between 2007 and 2016 in persons aged over 59 years living in the Community of Madrid (CM). We followed the European Committee on Antimicrobial Susceptibility Testing (EUCAST). The explanatory variables (age, sex, year of onset of symptoms, clinical presentation, serotypes, vaccination status) were taken from the Mandatory Notification System for Infectious Diseases System and from the Vaccination Information System. The cases were classified as either included in the 13-valent pneumococcal conjugate vaccine (PCV13) or not (nonPCV13). Associations between cases due to erythromycin-resistant serotypes and previous macrolide use (total, long and short-term) were adjusted with a logistic regression multivariate analysis. A total of 1,831 cases were identified, of whom 408 were erythromycin-resistant serotypes. PCV13 cases were associated with previous macrolide use (OR: 5.07), particularly long-acting types (OR: 8.61). NonPCV13 cases were associated with the use of total macrolides (OR: 3.48) and long-acting macrolides (OR: 4.26) suggesting that PCV13 did not reduce the IPD cases in patients with previous use of macrolides. Our results confirmed that previous macrolide consumption was associated with the presence of IPD due to erythromycin-resistant serotypes. The risk was higher with the use of long-term macrolides.

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Yu, Hong-Xia, Mao-Mao Zhao, Zeng-Hui Pu, Yuan-Rong Ju, and Yan Liu. "A study of community-acquired Mycoplasma pneumoniae in Yantai, China." Colombia Médica 49, no. 2 (June 1, 2018): 160–63. http://dx.doi.org/10.25100/cm.v49i2.3813.

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Introduction: Community-acquired pneumonia (CAP) is a global disease responsible for a large number of deaths, with significant economic impact. As diagnostic tools have increased in sensitivity, understanding of the etiology of CAP has begun to change. Mycoplasma pneumoniae is one of the major pathogens causing CAP. Macrolides and related antibiotics are first-line treatments for M. pneumoniae. Macrolide resistance has been spreading for 15 years and now occurs in worldwide. We undertook the first study on macrolide resistance of M. pneumoniae in Yantai. This may be helpful to determine the appropriate therapy for CAP in this population. Objective: To investigate the rate and mechanism of macrolide resistance in Yantai. Methods: Pharyngeal swab samples were collected from adult CAP patients. Samples were assayed by polymerase chain reaction (PCR) and cultivated to test for M. pneumoniae. Nested PCR was used to specifically amplify M. pneumoniae 23S rRNA gene fragments containing mutations, and amplicons were analyzed by CE-SSCP for macrolide resistance mutations. Results were confirmed by sequencing. Twenty-seven strains of M. pneumoniae were isolated and the activities of nine antibiotics against M. pneumoniae were tested in vitro. Results: Out of 128 samples tested, 27 were positive for M. pneumoniae. Mycoplasma 100% macrolides resistance to Mycoplasma pneumoniae. The mechanism of macrolides resistance was A2063G point mutation in the sequence directly binding to macrolides in the 23S rRNA V domain in vitro. The mean pyretolytic time for the fluoroquinolone group was 4.7 ±2.9 d, which was significantly shorter than 8.2 ±4.1 d for the azithromycin group. Conclusions: Macrolides are not the first-line treatment for M. pneumoniae respiratory tract infections in Yantai.

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MIJAC, V., N. OPAVSKI, M. MARKOVIC, I. GAJIC, Z. VASILJEVIC, T. SIPETIC, and M. BAJCETIC. "Trends in macrolide resistance of respiratory tract pathogens in the paediatric population in Serbia from 2004 to 2009." Epidemiology and Infection 143, no. 3 (May 9, 2014): 648–52. http://dx.doi.org/10.1017/s0950268814001125.

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SUMMARYWe report the first study of macrolide resistance in respiratory tract pathogens in a Serbian paediatric population. It included 5293 Streptococcus pneumoniae, 4297 Streptococcus pyogenes, 2568 Moraxella catarrhalis and 1998 Haemophilus influenzae isolates derived from the respiratory tract and 110 invasive isolates from children aged up to 18 years during 2004–2009. Over the 6-year period, a significant increase (P < 0·01) in macrolide resistance was found in both S. pneumoniae and S. pyogenes that reached 45% and 19%, respectively, in 2009. In the same period, consumption of macrolides increased continually from 2·46 to 5·8 defined daily dose/1000 inhabitants per day. The increase in macrolide resistance in S. pyogenes correlated with consumption of total macrolide and long-acting macrolides (r = 0·879, P = 0·05 and r = 0·922, P = 0·026, respectively). A similar trend was observed in pneumoccoci, although it did not reach statistical significance. The growing problem of macrolide resistance in pneumococci and S. pyogenes in Serbia requires further vigilant surveillance.

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Miyashita, Naoyuki, Hiroto Akaike, Hideto Teranishi, Kazunobu Ouchi, and Niro Okimoto. "Macrolide-Resistant Mycoplasma pneumoniae Pneumonia in Adolescents and Adults: Clinical Findings, Drug Susceptibility, and Therapeutic Efficacy." Antimicrobial Agents and Chemotherapy 57, no. 10 (July 29, 2013): 5181–85. http://dx.doi.org/10.1128/aac.00737-13.

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ABSTRACTWe investigated differences in the clinical findings between 30 patients with macrolide-resistantMycoplasma pneumoniaepneumonia and 43 patients with macrolide-sensitiveM. pneumoniaepneumonia in adolescents and adults. No differences in clinical presentation were observed between the two groups. Among patients with macrolide-resistantMycoplasma pneumoniaepneumonia, treatment was more effective in the groups that received quinolones and minocycline than in the group that received macrolides (P= 0.0361 andP= 0.0237, respectively).

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Choi, Yun Jung, Eun Hee Chung, Eun Lee, Chul-Hong Kim, Yong Ju Lee, Hyo-Bin Kim, Bong-Seong Kim, et al. "Clinical Characteristics of Macrolide-Refractory Mycoplasma pneumoniae Pneumonia in Korean Children: A Multicenter Retrospective Study." Journal of Clinical Medicine 11, no. 2 (January 8, 2022): 306. http://dx.doi.org/10.3390/jcm11020306.

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Mycoplasma pneumoniae is a major causative pathogen of community-acquired pneumonia in children, and the treatment of choice is macrolides. There is an increasing trend in reports of refractory clinical responses despite macrolide treatment due to the emergence of macrolide-resistant M. pneumoniae. Early discrimination of macrolide-refractory M. pneumoniae pneumonia (MrMP) from macrolide-sensitive M. pneumoniae pneumonia (MSMP) is vital; however, testing for macrolide susceptibility at the time of admission is not feasible. This study aimed to identify the characteristics of MrMP in Korean children, in comparison with those of MSMP. In this multicenter study, board-certified pediatric pulmonologists at 22 tertiary hospitals reviewed the medical records from 2010 to 2015 of 5294 children who were hospitalized with M. pneumoniae pneumonia and administered macrolides as the initial treatment. One-way analysis of variance and the Kruskal-Wallis test were used to compare differences between groups. Of 5294 patients (mean age, 5.6 years) included in this analysis, 240 (4.5%), 925 (17.5%), and 4129 (78.0%) had MrMP, macrolide-less effective M. pneumoniae pneumonia, and MSMP, respectively. Compared with the MSMP group, the MrMP group had a longer fever duration, overall (13.0 days) and after macrolide use (8.0 days). A higher proportion of MrMP patients had respiratory distress, pleural effusion, and lobar pneumonia. The mean aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and C-reactive protein levels were the highest in the MrMP group, along with higher incidences of extrapulmonary manifestations and atelectasis (during and post infection). Pre-existing conditions were present in 17.4% (n = 725/4159) of patients, with asthma being the most common (n = 334/4811, 6.9%). This study verified that MrMP patients show more severe initial radiographic findings and clinical courses than MSMP patients. MrMP should be promptly managed by agents other than macrolides.

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Ryu, Gwanghui, Eunkyu Lee, Song I. Park, Minhae Park, Sang Duk Hong, Yong Gi Jung, and Hyo Yeol Kim. "The Mechanism of Action and Clinical Efficacy of Low-Dose Long-Term Macrolide Therapy in Chronic Rhinosinusitis." International Journal of Molecular Sciences 24, no. 11 (May 30, 2023): 9489. http://dx.doi.org/10.3390/ijms24119489.

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Various chronic inflammatory airway diseases can be treated with low-dose, long-term (LDLT) macrolide therapy. LDLT macrolides can be one of the therapeutic options for chronic rhinosinusitis (CRS) due to their immunomodulatory and anti-inflammatory actions. Currently, various immunomodulatory mechanisms of the LDLT macrolide treatment have been reported, as well as their antimicrobial properties. Several mechanisms have already been identified in CRS, including reduced cytokines such as interleukin (IL)-8, IL-6, IL-1β, tumor necrosis factor-α, transforming growth factor-β, inhibition of neutrophil recruitment, decreased mucus secretion, and increased mucociliary transport. Although some evidence of effectiveness for CRS has been published, the efficacy of this therapy has been inconsistent across clinical studies. LDLT macrolides are generally believed to act on the non-type 2 inflammatory endotype of CRS. However, the effectiveness of LDLT macrolide treatment in CRS is still controversial. Here, we reviewed the immunological mechanisms related to CRS in LDLT macrolide therapy and the treatment effects according to the clinical situation of CRS.

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Falzari, Kanakeshwari, Zhaohai Zhu, Dahua Pan, Huiwen Liu, Poonpilas Hongmanee, and Scott G. Franzblau. "In Vitro and In Vivo Activities of Macrolide Derivatives against Mycobacterium tuberculosis." Antimicrobial Agents and Chemotherapy 49, no. 4 (April 2005): 1447–54. http://dx.doi.org/10.1128/aac.49.4.1447-1454.2005.

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ABSTRACTExisting macrolides have never shown definitive clinical efficacy in tuberculosis. Recent reports suggest that ribosome methylation is involved in macrolide resistance inMycobacterium tuberculosis, a mechanism that newer macrolides have been designed to overcome in gram-positive bacteria. Therefore, selected macrolides and ketolides (descladinose) with substitutions at positions 9, 11,12, and 6 were assessed for activity againstM. tuberculosis, and those with MICs of ≤4 μM were evaluated for cytotoxicity to Vero cells and J774A.1 macrophages. Several compounds with 9-oxime substitutions or aryl substitutions at position 6 or on 11,12 carbamates or carbazates demonstrated submicromolar MICs. For the three macrolide-ketolide pairs, macrolides demonstrated superior activity. Four compounds with low MICs and low cytotoxicity also effected significant reductions in CFU in infected macrophages. Active compounds were assessed for tolerance and the ability to reduce CFU in the lungs of BALB/c mice in an aerosol infection model. A substituted 11,12 carbazate macrolide demonstrated significant dose-dependent inhibition ofM. tuberculosisgrowth in mice, with a 10- to 20-fold reduction of CFU in lung tissue. Structure-activity relationships, some of which are unique toM. tuberculosis, suggest several synthetic directions for further improvement of antituberculosis activity. This class appears promising for yielding a clinically useful agent for tuberculosis.

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Rahman, Md, Veera Tiruveedhula, and James Cook. "Synthesis of Bisindole Alkaloids from the Apocynaceae Which Contain a Macroline or Sarpagine Unit: A Review." Molecules 21, no. 11 (November 14, 2016): 1525. http://dx.doi.org/10.3390/molecules21111525.

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BI, Y., L. H. ZHANG, L. K. HAMAKER, and J. M. COOK. "ChemInform Abstract: Enantiospecific Synthesis of (-)-Alstonerine and (+)-Macroline as Well as a Partial Synthesis of (+)-Villalstonine." ChemInform 26, no. 17 (August 18, 2010): no. http://dx.doi.org/10.1002/chin.199517208.

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Yamada, Takechiyo, Shigeharu Fujieda, Shigehito Mori, Hideyuki Yamamoto, and Hitoshi Saito. "Macrolide Treatment Decreased the Size of Nasal Polyps and IL-8 Levels in Nasal Lavage." American Journal of Rhinology 14, no. 3 (May 2000): 143–48. http://dx.doi.org/10.2500/105065800782102717.

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Recently, epidemiologic and experimental studies have been reported that long-term macrolides are effective for the treatment of chronic airway inflammatory diseases including diffuse panbronchiolitis, chronic rhinosinusitis, and cystic fibrosis (Jaffe A, Francis J, Rosenthal M, et al. Long-term azithromycin may improve lung function in children with cystic fibrosis. Lancet 351:420, 1998), and that macrolides can directly reduce the production of IL-8 by nasal epithelial cells (Suzuki H, Shimomura A, Ikeda K, et al. Inhibitory effect of macrolides on interleukin-8 secretion from cultured human nasal epithelial cells. Laryngoscope 107:1661–1666, 1997). In this study we administered macrolides with 14-membered rings to patients with nasal polyps due to chronic rhinosinusitis for at least 3 months and measured the IL-8 level in nasal lavage from those patients. The IL-8 levels in nasal lavage from patients with nasal polyps were reduced during macrolide treatment. There was significant correlation between decreased IL-8 levels in nasal lavage and the clinical effect of macrolides on the size of the nasal polyps. In the group whose polyps were reduced in size, the IL-8 levels dramatically decreased from 231.2 pg/mL to 44.0 pg/mL (p < 0.05), and were significantly higher before macrolide treatment than those in the group whose polyps showed no change (p < 0.005). This reduction in IL-8 may be an important aspect of the effect of macrolide treatment on nasal polyps in chronic rhinosinusitis.

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Wondrack, L., M. Massa, B. V. Yang, and J. Sutcliffe. "Clinical strain of Staphylococcus aureus inactivates and causes efflux of macrolides." Antimicrobial Agents and Chemotherapy 40, no. 4 (April 1996): 992–98. http://dx.doi.org/10.1128/aac.40.4.992.

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Searching through a collection of 124 Staphylococcus aureus clinical strains, we found one isolate, strain 01A1032, that inactivates 14- and 16-membered macrolides. The products of inactivation were purified from supernatant fluids of cultures exposed to erythromycin for 3 h and were found to be identical to products of inactivation from Escherichia coli strains that encode either an EreA or EreB esterase. Further, strain 01A1032 was shown to be resistant to azithromycin, a 15-membered macrolide, by an alternate mechanism, efflux. Thus, strain 01A1032 harbors determinants encoding an esterase activity that hydrolyzes 14- and 16-membered macrolides and a macrolide efflux system.

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Karaatmaca, Betül, Şule büyük yaytokgil, İlknur Külhaş Çelik, Özge Yılmaz Topal, Ersoy Civelek, Müge Toran, and Emine Dibek Mısırlıoğlu. "Macrolide Allergy in Children and the Negative Predictive Value of Drug Provocation Tests in Mild Index Reactions." Asthma Allergy Immunology 19, no. 2 (August 23, 2021): 92–99. http://dx.doi.org/10.21911/aai.655.

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ABSTRACT Objective: Macrolide allergy is rarely reported, and there is limited knowledge of hypersensitivity reactions (HRs) in children. The negative predictive value (NPV) of drug provocation tests (DPTs) for macrolides is unresolved. We aim to evaluate the clinical features of macrolide allergy in children, and determine the NPV of macrolide DPTs. Materials and Methods: Pediatric patients who were referred to our allergy department with a suspicion of macrolide allergy were evaluated by DPTs with or without prior skin tests between 2011 and 2020. Characteristics of the HRs and patients, the results of skin and DPTs were recorded. At least three months after evaluation of the patients with allergy work up, telephone interviews were performed. Patients were asked whether they had reused the suspected macrolide or not. Patients who reported HR during subsequent drug intake were invited for reevaluation. Results: A total of 160 children (161 reactions) (55.6% male) with a suspicion of macrolide allergy were enrolled for the study, and all children had a mild index reaction. The median age was 48 (18-102) months, and the median time between the suspected allergic reaction and allergy work-up was 3 (2-8) months. The most frequently reported suspected agent was clarithromycin, in 151 patients (94.4%). Macrolide allergy was confirmed in 8 (5%) patients. Only one patient reported skin eruptions upon reuse despite a negative DPT and he was invited to be reevaluated. A second DPT was performed resulting in urticarial lesions. The NPV was found to be 97.4% for negative DPT with macrolides. Conclusion: Confirmed macrolide allergy is rare in children, and DPTs are the gold standard to assess suspected macrolide allergy. The NPV of macrolide provocation tests seems to be high in children. Keywords: Children, drug hypersensitivity, drug provocation test, macrolide, negative predictive value

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Brown-Elliott, Barbara A., Sruthi Vasireddy, Ravikiran Vasireddy, Elena Iakhiaeva, Susan T. Howard, Kevin Nash, Nicholas Parodi, et al. "Utility of Sequencing theerm(41) Gene in Isolates of Mycobacterium abscessus subsp. abscessus with Low and Intermediate Clarithromycin MICs." Journal of Clinical Microbiology 53, no. 4 (February 4, 2015): 1211–15. http://dx.doi.org/10.1128/jcm.02950-14.

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Theerm(41) gene confers inducible macrolide resistance inMycobacterium abscessussubsp.abscessus, calling into question the usefulness of macrolides for treatingM. abscessussubsp.abscessusinfections. With an extended incubation (14 days), isolates with MICs of ≥8 μg/ml are considered macrolide resistant by current CLSI guidelines. Our goals were to determine the incidence of macrolide susceptibility in U.S. isolates, the validity of currently accepted MIC breakpoints, and theerm(41) sequences associated with susceptibility. Of 349 isolates (excluding those with 23S rRNA gene mutations), 85 (24%) had clarithromycin MICs of ≤8 μg/ml. Sequencing of theerm(41) genes from these isolates, as well as from isolates with MICs of ≥16 μg/ml, including ATCC 19977T, revealed 10 sequevars. The sequence in ATCC 19977Twas designated sequevar (type) 1; most macrolide-resistant isolates were of this type. Seven sequevars contained isolates with MICs of >16 μg/ml. The T28C substitution inerm(41), previously associated with macrolide susceptibility, was identified in 62 isolates (18%) comprising three sequevars, with MICs of ≤2 (80%), 4 (10%), and 8 (10%) μg/ml. No other nucleotide substitution was associated with macrolide susceptibility. We recommend that clarithromycin susceptibility breakpoints forM. abscessussubsp.abscessusbe changed from ≤2 to ≤4 μg/ml and that isolates with an MIC of 8 μg/ml have repeat MIC testing orermsequencing performed. Our studies suggest that macrolides are useful for treating approximately 20% of U.S. isolates ofM. abscessussubsp.abscessus. Sequencing of theermgene ofM. abscessussubsp.abscessuswill predict inducible macrolide susceptibility.

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