medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2024-102medsovet-8317Research ArticleРАЦИОНАЛЬНАЯ ФАРМАКОТЕРАПИЯRATIONAL PHARMACOTHERAPYВнебольничная пневмония в амбулаторных условиях: актуальные вопросы антибактериальной терапииCommunity-acquired pneumonia in outpatients: topical issues of antibacterial therapyhttps://orcid.org/0000-0003-1224-1904БелоцерковскаяЮ. Г.BelotserkovskayaYu. G.

Белоцерковская Юлия Геннадьевна - к.м.н., доцент кафедры пульмонологии.

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1

Yulia G. Belotserkovskaya - Cand. Sci. (Med.), Associate Professor, Department of Pulmonology, Russian Medical Academy of Continuous Professional Education.

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993

belo-yuliya@yandex.ruhttps://orcid.org/0000-0001-9675-7451РомановскихА. Г.RomanovskikhA. G.

Романовских Анна Геннадьевна - к.м.н., доцент кафедры пульмонологии.

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1

Anna G. Romanovskikh - Cand. Sci. (Med.), Associate Professor, Department of Pulmonology, Russian Medical Academy of Continuous Professional Education.

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993

https://orcid.org/0000-0001-8954-5303СмирновИ. П.SmirnovI. P.

Смирнов Игорь Павлович - ассистент кафедры пульмонологии.

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1

Igor P. Smirnov - Assistant of the Department of Pulmonology, Russian Medical Academy of Continuous Professional Education.

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993

Российская медицинская академия непрерывного профессионального образованияРоссияRussian Medical Academy of Continuous Professional EducationRussian Federation20240506202409178183Copyright © Белоцерковская Ю.Г., Романовских А.Г., Смирнов И.П., 20242024Белоцерковская Ю.Г., Романовских А.Г., Смирнов И.П.Belotserkovskaya Y.G., Romanovskikh A.G., Smirnov I.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/8317

Внебольничная пневмония (ВП) является одной из ведущих причин заболеваемости и смертности во всем мире. Успешное лечение больных ВП во многом определяется правильным выбором места лечения (амбулаторно или в стационаре) и корректной стартовой эмпирической терапией с учетом предсказуемого спектра потенциальных возбудителей ВП. В статье приводятся современные данные по этиологической структуре нетяжелых ВП. Большинство пациентов с ВП получают медицинскую помощь амбулаторно, что определяется с учетом клинического статуса и ограниченного числа лабораторных данных, позволяющих минимизировать риск развития неблагоприятных исходов при ВП. Отсутствие микробиологического диагноза при нетяжелом течении ВП не приводит к снижению эффективности эмпирической антибактериальной терапии в амбулаторных условиях. В статье освещаются актуальные клинические рекомендации по выбору эмпирической антибактериальной терапии ВП в амбулаторных условиях. Амоксициллин – полусинтетический пенициллин, который, в т. ч. в комбинации с ингибитором β-лактамазы клавулановой кислотой, является наиболее доступным и широко используемым пенициллином в различных странах. С учетом клинических рекомендаций амоксициллин, в т. ч. в комбинации с ингибитором β-лактамазы, является препаратом выбора для стартовой эмпирической терапии большинства больных ВП в амбулаторных условиях. Пероральный способ наиболее распространен и предпочтителен для доставки антибиотика при нетяжелой ВП. Диспергируемые формы таблеток имеют определенные преимущества, в т. ч. более легкий прием у пациентов, испытывающих трудности с глотанием, таких как пожилые люди, больные после инсульта, дети. Оценка биологической эквивалентности показала сходные параметры фармакокинетики амоксициллина и амоксициллина в комбинации с клавулановой кислотой в форме диспергируемых таблеток и в оригинальной форме таблеток, покрытых пленочной оболочкой.

Community-acquired pneumonia (CAP) is one of the leading causes of morbidity and mortality worldwide. Successful treatment of patients with CAP is mainly determined by the correct choice of the place of treatment (outpatient or inpatient) and the correct initial empirical therapy, considering the predictable spectrum of potential pathogens of CAP. The article provides up-to-date data on the etiological structure of non-severe CAP. Most patients with CAP receive outpatient medical care, which is determined by their clinical status and a limited number of laboratory data for minimizing the risk of adverse outcomes in CAP. The absence of a microbiological diagnosis in a mild course of CAP does not lead to a decrease in the effectiveness of empirical antibacterial therapy in outpatient settings. The article highlights current clinical recommendations on the choice of empirical antibiotic therapy for CAP in outpatients. Amoxicillin is a semi-synthetic penicillin, which, including in combination with the beta-lactamase inhibitor clavulanic acid, is the most affordable and widely used penicillin in various countries. According to clinical recommendations, amoxicillin, including in combination with a β-lactamase inhibitor, is the drug of choice for the initial empirical therapy of most outpatients with CAP. The oral route is the most common and preferred for antibiotic delivery in mild CAP. Dispersible forms of tablets have certain advantages, including easier intake in patients with difficulty swallowing, such as the elderly, stroke patients, and children. The assessment of biological equivalence showed similar pharmacokinetic parameters of Amoxicillin and Amoxicillin in combination with clavulanic acid in the form of dispersible tablets and in the original form of film-coated tablets.

внебольничная пневмонияэтиологияэмпирическая антибактериальная терапияамоксициллиндиспергируемые формы антибиотиковcommunity-acquired pneumoniaetiologyempirical antibacterial therapyamoxicillindispersible forms of antibioticsReferencesTorres A, Cilloniz C, Niederman MS, Chalmers JD, Menéndez R, Wunderink RG, van der Poll T. Pneumonia. Nat Rev Dis Primers. 2021;7:25. https://doi.org/10.1038/s41572-021-00259-0.Torres A, Cilloniz C, Niederman MS, Chalmers JD, Menéndez R, Wunderink RG, van der Poll T. Pneumonia. Nat Rev Dis Primers. 2021;7:25. https://doi.org/10.1038/s41572-021-00259-0.Ferrer M, Travierso C, Cilloniz C, Gabarrus A, Ranzani OT, Polverino E et al. Severe community-acquired pneumonia: characteristics and prognostic factors in ventilated and non-ventilated patients. PLoS ONE. 2018;13:e0191721. https://doi.org/10.1371/journal.pone.0191721.Ferrer M, Travierso C, Cilloniz C, Gabarrus A, Ranzani OT, Polverino E et al. Severe community-acquired pneumonia: characteristics and prognostic factors in ventilated and non-ventilated patients. PLoS ONE. 2018;13:e0191721. https://doi.org/10.1371/journal.pone.0191721.Simonetti AF, Garcia‐Vidal C, Viasus D García-Somoza D, Dorca J, Gudiol F, Carratalà J. Declining mortality among hospitalized patients with community-acquired pneumonia. Clin Microbiol Infect. 2016;22(6):567.e1–e7. https://doi.org/10.1016/j.cmi.2016.03.015.Simonetti AF, Garcia‐Vidal C, Viasus D García-Somoza D, Dorca J, Gudiol F, Carratalà J. Declining mortality among hospitalized patients with community-acquired pneumonia. Clin Microbiol Infect. 2016;22(6):567.e1–e7. https://doi.org/10.1016/j.cmi.2016.03.015.Cilloniz C, Ferrer M, Liapikou A, Garcia-Vidal C, Gabarrus A, Ceccato A et al. Acute respiratory distress syndrome in mechanically ventilated patients with community‐ acquired pneumonia. Eur Respir J. 2018;51(3):1702215. https://doi.org/10.1183/13993003.02215-2017.Cilloniz C, Ferrer M, Liapikou A, Garcia-Vidal C, Gabarrus A, Ceccato A et al. Acute respiratory distress syndrome in mechanically ventilated patients with community‐ acquired pneumonia. Eur Respir J. 2018;51(3):1702215. https://doi.org/10.1183/13993003.02215-2017.Chen J, Li X, Wang W, Jia Y, Lin F, Xu J. The prevalence of respiratory pathogens in adults with community-acquired pneumonia in an outpatient cohort. Infect Drug Resist. 2019;12:2335–2341. https://doi.org/10.2147/IDR.S213296.Chen J, Li X, Wang W, Jia Y, Lin F, Xu J. The prevalence of respiratory pathogens in adults with community-acquired pneumonia in an outpatient cohort. Infect Drug Resist. 2019;12:2335–2341. https://doi.org/10.2147/IDR.S213296.Fujikura Y, Somekawa K, Manabe T, Horita N, Takahashi H, Higa F et al. Aetiological agents of adult community-acquired pneumonia in Japan: systematic review and meta-analysis of published data. BMJ Open Respir Res. 2023;10(1):e001800. https://doi.org/10.1136/bmjresp-2023-001800.Fujikura Y, Somekawa K, Manabe T, Horita N, Takahashi H, Higa F et al. Aetiological agents of adult community-acquired pneumonia in Japan: systematic review and meta-analysis of published data. BMJ Open Respir Res. 2023;10(1):e001800. https://doi.org/10.1136/bmjresp-2023-001800.Gadsby NJ, Russell CD, McHugh MP, Mark H, Conway Morris A, Laurenson IF et al. Comprehensive molecular testing for respiratory pathogens in community-acquired pneumonia. Clin Infect Dis. 2016;62(7):817–823. https://doi.org/10.1093/cid/civ1214.Gadsby NJ, Russell CD, McHugh MP, Mark H, Conway Morris A, Laurenson IF et al. Comprehensive molecular testing for respiratory pathogens in community-acquired pneumonia. Clin Infect Dis. 2016;62(7):817–823. https://doi.org/10.1093/cid/civ1214.Ferreira-Coimbra J, Sarda C, Rello J. Burden of Community-Acquired Pneumonia and Unmet Clinical Needs. Adv Ther. 2020;37(4):1302–1318. https://doi.org/10.1007/s12325-020-01248-7.Ferreira-Coimbra J, Sarda C, Rello J. Burden of Community-Acquired Pneumonia and Unmet Clinical Needs. Adv Ther. 2020;37(4):1302–1318. https://doi.org/10.1007/s12325-020-01248-7.Sahuquillo-Arce JM, Menéndez R, Méndez R, Amara-Elori I, Zalacain R, Capelastegui A et al. Age-related risk factors for bacterial aetiology in community-acquired pneumonia. Respirology. 2016;21(8):1472–1479. https://doi.org/10.1111/resp.12851.Sahuquillo-Arce JM, Menéndez R, Méndez R, Amara-Elori I, Zalacain R, Capelastegui A et al. Age-related risk factors for bacterial aetiology in community-acquired pneumonia. Respirology. 2016;21(8):1472–1479. https://doi.org/10.1111/resp.12851.Harris AM, Beekmann SE, Polgreen PM, Moore MR. Rapid urine antigen testing for Streptococcus pneumoniae in adults with community-acquired pneumonia: clinical use and barriers. Diagn Microbiol Infect Dis. 2014;79:454–457. https://doi.org/10.1016/j.diagmicrobio.2014.05.008.Harris AM, Beekmann SE, Polgreen PM, Moore MR. Rapid urine antigen testing for Streptococcus pneumoniae in adults with community-acquired pneumonia: clinical use and barriers. Diagn Microbiol Infect Dis. 2014;79:454–457. https://doi.org/10.1016/j.diagmicrobio.2014.05.008.Welte T, Torres A, Nathwani D. Clinical and economic burden of community-acquired pneumonia among adults in Europe. Thorax. 2012;67(1):71–79. https://doi.org/10.1136/thx.2009.129502.Welte T, Torres A, Nathwani D. Clinical and economic burden of community-acquired pneumonia among adults in Europe. Thorax. 2012;67(1):71–79. https://doi.org/10.1136/thx.2009.129502.Song JH, Thamlikitkul V, Hsueh PR. Clinical and economic burden of community-acquired pneumonia amongst adults in the Asia-Pacific region. Int J Antimicrob Agents. 2011;38(2):108–117. https://doi.org/10.1016/j.ijantimicag.2011.02.017.Song JH, Thamlikitkul V, Hsueh PR. Clinical and economic burden of community-acquired pneumonia amongst adults in the Asia-Pacific region. Int J Antimicrob Agents. 2011;38(2):108–117. https://doi.org/10.1016/j.ijantimicag.2011.02.017.Isturiz RE, Luna CM, Ramirez J. Clinical and economic burden of pneumonia among adults in Latin America. Int J Infect Dis. 2010;14(10):e852–e856. https://doi.org/10.1016/j.ijid.2010.02.2262.Isturiz RE, Luna CM, Ramirez J. Clinical and economic burden of pneumonia among adults in Latin America. Int J Infect Dis. 2010;14(10):e852–e856. https://doi.org/10.1016/j.ijid.2010.02.2262.Arnold FW, Summersgill JT, Lajoie AS, Peyrani P, Marrie TJ, Rossi P et al. A worldwide perspective of atypical pathogens in community-acquired pneumonia. Am J Respir Crit Care Med. 2007;175(10):1086–1093. https://doi.org/10.1164/rccm.200603-350OC.Arnold FW, Summersgill JT, Lajoie AS, Peyrani P, Marrie TJ, Rossi P et al. A worldwide perspective of atypical pathogens in community-acquired pneumonia. Am J Respir Crit Care Med. 2007;175(10):1086–1093. https://doi.org/10.1164/rccm.200603-350OC.Blazquez RM, Espinosa FJ, Martinez-Toldos CM, Alemany L, García-Orenes MC, Segovia M. Sensitivity of urinary antigen test in relation to clinical severity in a large outbreak of Legionella pneumonia in Spain. Eur J Clin Microbiol Infect Dis. 2005;24:488–491. https://doi.org/10.1007/s10096-005-1361-3.Blazquez RM, Espinosa FJ, Martinez-Toldos CM, Alemany L, García-Orenes MC, Segovia M. Sensitivity of urinary antigen test in relation to clinical severity in a large outbreak of Legionella pneumonia in Spain. Eur J Clin Microbiol Infect Dis. 2005;24:488–491. https://doi.org/10.1007/s10096-005-1361-3.Авдеев СН, Дехнич АВ, Зайцев АА, Козлов РС, Рачина СА, Руднов ВА и др. Внебольничная пневмония у взрослых: клинические рекомендации. 2021. 133 с. Режим доступа: https://spulmo.ru/upload/kr/Pneumonia_2021.pdf.Авдеев СН, Дехнич АВ, Зайцев АА, Козлов РС, Рачина СА, Руднов ВА и др. Внебольничная пневмония у взрослых: клинические рекомендации. 2021. 133 с. Режим доступа: https://spulmo.ru/upload/kr/Pneumonia_2021.pdf.Shindo Y, Ito R, Kobayashi D, Ando M, Ichikawa M, Shiraki A et al. Risk factors for drug-resistant pathogens in community-acquired and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2013;188(8):985–995. https://doi.org/10.1164/rccm.201301-0079OC.Shindo Y, Ito R, Kobayashi D, Ando M, Ichikawa M, Shiraki A et al. Risk factors for drug-resistant pathogens in community-acquired and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2013;188(8):985–995. https://doi.org/10.1164/rccm.201301-0079OC.Cao B, Ren LL, Zhao F, Gonzalez R, Song SF, Bai L et al. Viral and Mycoplasma pneumoniae community-acquired pneumonia and novel clinical outcome evaluation in ambulatory adult patients in China. Eur J Clin Microbiol Infect Dis. 2010;29(11):1443–1448. https://doi.org/10.1007/s10096-010-1003-2.Cao B, Ren LL, Zhao F, Gonzalez R, Song SF, Bai L et al. Viral and Mycoplasma pneumoniae community-acquired pneumonia and novel clinical outcome evaluation in ambulatory adult patients in China. Eur J Clin Microbiol Infect Dis. 2010;29(11):1443–1448. https://doi.org/10.1007/s10096-010-1003-2.Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet DL et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis. 2018;18(3):318–327. https://doi.org/10.1016/S1473-3099(17)30753-3.Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet DL et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis. 2018;18(3):318–327. https://doi.org/10.1016/S1473-3099(17)30753-3.Mandell LM, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC et al. Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clin Infect Dis. 2007;44(Suppl. 2):S27–S72. https://doi.org/10.1086/511159.Mandell LM, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC et al. Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults. Clin Infect Dis. 2007;44(Suppl. 2):S27–S72. https://doi.org/10.1086/511159.Athlin S, Lidman C, Lundqvist A, Naucler P, Nilsson AC, Spindler C et al. Management of community-acquired pneumonia in immunocompetent adults: updated Swedish guidelines 2017. Infect Dis (Lond). 2018;50(4):247–272. https://doi.org/10.1080/23744235.2017.1399316.Athlin S, Lidman C, Lundqvist A, Naucler P, Nilsson AC, Spindler C et al. Management of community-acquired pneumonia in immunocompetent adults: updated Swedish guidelines 2017. Infect Dis (Lond). 2018;50(4):247–272. https://doi.org/10.1080/23744235.2017.1399316.Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM et al. Community‐acquired pneumonia requiring hospitalization among US adults. N Engl J Med. 2015;373(5):415–427. https://doi.org/10.1056/ NEJMoa1500245.Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM et al. Community‐acquired pneumonia requiring hospitalization among US adults. N Engl J Med. 2015;373(5):415–427. https://doi.org/10.1056/ NEJMoa1500245.Rouzé A, Martin‐Loeches I, Povoa P, Makris D, Artigas A, Bouchereau M et al. Relationship between SARS‐CoV‐2 infection and the incidence of ventilator‐associated lower respiratory tract infections: a European multicenter cohort study. Intensive Care Med. 2021;47(2):188–198. https://doi.org/10.1007/s00134-020-06323-9.Rouzé A, Martin‐Loeches I, Povoa P, Makris D, Artigas A, Bouchereau M et al. Relationship between SARS‐CoV‐2 infection and the incidence of ventilator‐associated lower respiratory tract infections: a European multicenter cohort study. Intensive Care Med. 2021;47(2):188–198. https://doi.org/10.1007/s00134-020-06323-9.Авдеев СН, Адамян ЛВ, Алексеева ЕИ, Багненко СФ, Баранов АА, Баранова НН и др. Профилактика, диагностика и лечение новой коронавирусной инфекции (COVID­19): временные методические рекомендации. 2023. 250 с. Режим доступа: https://static-0.minzdrav.gov.ru/system/attachments/attaches/000/064/610/original/ВМР_COVID-19_V18.pdf.Авдеев СН, Адамян ЛВ, Алексеева ЕИ, Багненко СФ, Баранов АА, Баранова НН и др. Профилактика, диагностика и лечение новой коронавирусной инфекции (COVID­19): временные методические рекомендации. 2023. 250 с. Режим доступа: https://static-0.minzdrav.gov.ru/system/attachments/attaches/000/064/610/original/ВМР_COVID-19_V18.pdf.Martin-Loeches I, Torres A, Nagavci B, Aliberti S, Antonelli M, Bassetti M et al. ERS/ESICM/ESCMID/ALAT guidelines for the management of severe community-acquired pneumonia. Intensive Care Med. 2023;49(6):615–632. https://doi.org/10.1007/s00134-023-07033-8.Martin-Loeches I, Torres A, Nagavci B, Aliberti S, Antonelli M, Bassetti M et al. ERS/ESICM/ESCMID/ALAT guidelines for the management of severe community-acquired pneumonia. Intensive Care Med. 2023;49(6):615–632. https://doi.org/10.1007/s00134-023-07033-8.Bjarnason A, Westin J, Lindh M, Andersson LM, Kristinsson KG, Löve A et al. Incidence, etiology, and outcomes of community-acquired pneumonia: A population-based study. Open Forum Infect Dis. 2018;5(2):ofy010. https://doi.org/10.1093/ofid/ofy010.Bjarnason A, Westin J, Lindh M, Andersson LM, Kristinsson KG, Löve A et al. Incidence, etiology, and outcomes of community-acquired pneumonia: A population-based study. Open Forum Infect Dis. 2018;5(2):ofy010. https://doi.org/10.1093/ofid/ofy010.Eshwara VK, Mukhopadhyay C, Rello J. Community-acquired bacterial pneumonia in adults: An update. Indian J Med Res. 2020;151(4):287–302. https://doi.org/10.4103/ijmr.IJMR_1678_19.Eshwara VK, Mukhopadhyay C, Rello J. Community-acquired bacterial pneumonia in adults: An update. Indian J Med Res. 2020;151(4):287–302. https://doi.org/10.4103/ijmr.IJMR_1678_19.Lim WS, van der Eerden MM, Laing R, Boersma WG, Karalus N, Town GI et al. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax. 2003;58(5):377–382. https://doi.org/10.1136/thorax.58.5.377.Lim WS, van der Eerden MM, Laing R, Boersma WG, Karalus N, Town GI et al. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax. 2003;58(5):377–382. https://doi.org/10.1136/thorax.58.5.377.Sharland M, Pulcini C, Harbarth S, Zeng M, Gandra S, Mathur S, Magrini N. Classifying antibiotics in the WHO essential medicines list for optimal use-be AWaRe. Lancet Infect Dis. 2018;18(1):18–20. https://doi.org/10.1016/S1473-3099(17)30724-7.Sharland M, Pulcini C, Harbarth S, Zeng M, Gandra S, Mathur S, Magrini N. Classifying antibiotics in the WHO essential medicines list for optimal use-be AWaRe. Lancet Infect Dis. 2018;18(1):18–20. https://doi.org/10.1016/S1473-3099(17)30724-7.Bodey GP, Nance J. Amoxicillin: in vitro and pharmacological studies. Antimicrob Agents Chemother. 1972;1(4):358–362. https://doi.org/10.1128/AAC.1.4.358.Bodey GP, Nance J. Amoxicillin: in vitro and pharmacological studies. Antimicrob Agents Chemother. 1972;1(4):358–362. https://doi.org/10.1128/AAC.1.4.358.Ambler RP. The structure of beta-lactamases. Philos Trans R Soc Lond B Biol Sci. 1980;289(1036):321–331. https://doi.org/10.1098/rstb.1980.0049.Ambler RP. The structure of beta-lactamases. Philos Trans R Soc Lond B Biol Sci. 1980;289(1036):321–331. https://doi.org/10.1098/rstb.1980.0049.Jaurin B, Grundstrom T. ampC cephalosporinase of Escherichia coli K-12 has a different evolutionary origin from that of beta-lactamases of the penicillinase type. Proc Natl Acad Sci U S A. 1981;78(8):4897–4901. https://doi.org/10.1073/pnas.78.8.4897.Jaurin B, Grundstrom T. ampC cephalosporinase of Escherichia coli K-12 has a different evolutionary origin from that of beta-lactamases of the penicillinase type. Proc Natl Acad Sci U S A. 1981;78(8):4897–4901. https://doi.org/10.1073/pnas.78.8.4897.Ouellette M, Bissonnette L, Roy PH. Precise insertion of antibiotic resistance determinants into Tn21-like transposons: nucleotide sequence of the OXA-1 beta-lactamase gene. Proc Natl Acad Sci U S A. 1987;84(21):7378–7382. https://doi.org/10.1073/pnas.84.21.7378.Ouellette M, Bissonnette L, Roy PH. Precise insertion of antibiotic resistance determinants into Tn21-like transposons: nucleotide sequence of the OXA-1 beta-lactamase gene. Proc Natl Acad Sci U S A. 1987;84(21):7378–7382. https://doi.org/10.1073/pnas.84.21.7378.Hall BG, Barlow M. Revised Ambler classification of {beta}-lactamases. J Antimicrob Chemother. 2005;55(6):1050–1051. https://doi.org/10.1093/jac/dki130.Hall BG, Barlow M. Revised Ambler classification of {beta}-lactamases. J Antimicrob Chemother. 2005;55(6):1050–1051. https://doi.org/10.1093/jac/dki130.Salvo F, Polimeni G, Moretti U, Conforti A, Leone R, Leoni O et al. Adverse drug reactions related to amoxicillin alone and in association with clavulanic acid: data from spontaneous reporting in Italy. J Antimicrob Chemother. 2007;60(1):121–126. https://doi.org/10.1093/jac/dkm111.Salvo F, Polimeni G, Moretti U, Conforti A, Leone R, Leoni O et al. Adverse drug reactions related to amoxicillin alone and in association with clavulanic acid: data from spontaneous reporting in Italy. J Antimicrob Chemother. 2007;60(1):121–126. https://doi.org/10.1093/jac/dkm111.Hannan PA, Khan JA, Khan A, Safiullah S. Oral Dispersible System: A New Approach in Drug Delivery System. Indian J Pharm Sci. 2016;78(1):2–7. Available at: https://www.ijpsonline.com/articles/oral-dispersible-system-a-new-approach-in-drug-delivery-system.pdf.Hannan PA, Khan JA, Khan A, Safiullah S. Oral Dispersible System: A New Approach in Drug Delivery System. Indian J Pharm Sci. 2016;78(1):2–7. Available at: https://www.ijpsonline.com/articles/oral-dispersible-system-a-new-approach-in-drug-delivery-system.pdf.Bradoo R, Shahani S, Poojary S, Deewan B, Sudarshan S. Fast dissolving drug delivery systems. JAMA India. 2001;4(10):27–31.Bradoo R, Shahani S, Poojary S, Deewan B, Sudarshan S. Fast dissolving drug delivery systems. JAMA India. 2001;4(10):27–31.Sourgens H, Steinbrede H, Verschoor JSC, Bertola MA, Rayer B. Bioequivalence study of a novel Solutab tablet formulation of amoxicillin/clavulanic acid versus the originator film-coated tablet. Int J Clin Pharmacol Ther. 2001;39(2):75–82. https://doi.org/10.5414/cpp39075.Sourgens H, Steinbrede H, Verschoor JSC, Bertola MA, Rayer B. Bioequivalence study of a novel Solutab tablet formulation of amoxicillin/clavulanic acid versus the originator film-coated tablet. Int J Clin Pharmacol Ther. 2001;39(2):75–82. https://doi.org/10.5414/cpp39075.

The authors declare that there are no conflicts of interest present.