Etiology and efficacy of anti-microbial treatment for community-acquired pneumonia in adults requiring hospital admission in Ukraine

Igor Kaidashev; Anna Lavrenko; Tatiana Baranovskaya; Victor Blazhko; Nataliia Digtiar; Oleksandr Dziublyk; Nataliia Gerasymenko; Liudmyla Iashyna; Volodymyr Kryvetskyi; Lesya Kuryk; Victoria Rodionova; Roman Stets; Ivan Vyshnyvetskyy; Yurii Feshchenko

doi:10.23750/abm.v93i2.13137

Etiology and efficacy of anti-microbial treatment for community-acquired pneumonia in adults requiring hospital admission in Ukraine

Authors

Igor Kaidashev Poltava State Medical University, Poltava https://orcid.org/0000-0002-4708-0859
Anna Lavrenko Poltava State Medical University, Poltava https://orcid.org/0000-0001-7025-1612
Tatiana Baranovskaya Kyiv City Clinical Hospital №17, Department of Clinical Pulmonology, Kyiv
Victor Blazhko Municipal non-profit enterprise “City Clinical Hospital №13” of Kharkiv City Council, Pulmonology department №2, Kharkiv https://orcid.org/0000-0002-6856-3825
Nataliia Digtiar Poltava State Medical University, Poltava https://orcid.org/0000-0002-8238-1876
Oleksandr Dziublyk
Nataliia Gerasymenko Poltava State Medical University, Poltava
Liudmyla Iashyna State Institution “National Institute of Tuberculosis and Pulmonology. F.G. Yanovsky National Academy of Medical Sciences of Ukraine”, Kyiv
Volodymyr Kryvetskyi National Pirogov Memorial Medical University, Vinnytsia https://orcid.org/0000-0003-1284-6540
Lesya Kuryk State Institution “National Institute of Tuberculosis and Pulmonology. F.G. Yanovsky National Academy of Medical Sciences of Ukraine”, Kyiv
Victoria Rodionova Dnipropetrovsk State Medical Academy, Dnipro
Roman Stets Municipal institution “6th city clinical hospital”, Zaporizhzhia
Ivan Vyshnyvetskyy Bogomolets National Medical University, Kyiv; Municipal Institution Central City Hospital №1, Zhytomyr https://orcid.org/0000-0001-7228-3052
Yurii Feshchenko State Institution “National Institute of Tuberculosis and Pulmonology. F.G. Yanovsky National Academy of Medical Sciences of Ukraine”, Kyiv https://orcid.org/0000-0002-9711-2003

DOI: https://doi.org/10.23750/abm.v93i2.13137

Keywords:

antibiotics, delafloxacin, empiric antimicrobial therapy, moxifloxacin, community-acquired pneumonia

Abstract

Background and aim: Empiric therapy of community-acquired pneumonia (CAP) remains the standard care and guidelines are mostly based on published data from the United States or Europe. In this study, we determined the bacterial etiology of CAP and evaluated the clinical outcomes under antimicrobial treatment of CAP in Ukraine.

Methods: A total of 98 adult subjects with CAP and PORT risk II-IV were recruited for the study. The sputum diagnostic samples were obtained from all patients for causative pathogen identification. Subjects were randomly assigned in a 1:1 ratio to receive delafloxacin 300 mg (n=51) or moxifloxacin 400 mg (n=47) with blinding placebo. The switch to oral treatment was after a minimum of 6 IV doses according to clinical criteria. The total duration of antibacterial treatment was 5-10 days. In vitro susceptibility of pathogens to delafloxacin and other comparator antibiotics was determined.

Results: The most frequently isolated pathogens in adults with CAP were S. pneumoniae – 19.5%, M. pneumoniae – 15.3%, H. influenzae – 13.2%, S. aureus – 10.5%, K. pneumoniae – 10.1%, and H. parainfluenzae – 6.4%. All isolates of S. pneumoniae, S. aureus, M. pneumoniae had sufficient susceptibility to appropriate antibiotics. 9.0% of H. influenzae strains were susceptible to azithromycin. 94.8 % of patients had a successful clinical response to delafloxacin at the end of treatment and 93.9 % – at test-of-cure.

Conclusions: In Ukraine, the major bacterial agents that induced CAP in adults were S. pneumoniae, M. pneumoniae, H. influenzae, S. aureus, K. pneumoniae, H. parainfluenzae, E. cloacae, L. pneumophila. Delafloxacin is a promising effective antibiotic for monotherapy for CAP in adults and could be used in cases of antimicrobial-resistant strains.

References

Restrepo MI, Faverio P, Anzueto A. Long-term prognosis in community-acquired pneumonia. Curr Opin Infect Dis. 2013; 26(2): 151-158.

Zar HJ, Madhi SA, Aston SJ, Gordon SB. Pneumonia in low and middle income countries: progress and challenges. Thorax. 2013; 68(11): 1052-1056.

Welte T, Torres A, Nathwani D. Clinical and economic burden of community-acquired pneumonia among adults in Europe. Thorax. 2012; 67(1): 71-9.

Jain S, Self WH, Wunderink RG, et al.; CDC EPIC Study Team. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. N Engl J Med. 2015; 373(5): 415-27.

Brown JS. Geography and the aetiology of community-acquired pneumonia. Respirology. 2009; 14(8): 1068-71.

Akter S, Shamsuzzaman SM, Jahan F. Community acquired bacterial pneumonia: aetiology, laboratory detection and antibiotic susceptibility pattern. Malays J Pathol. 2014; 36(2): 97-103.

Peto L, Nadjm B, Horby P, et al. The bacterial aetiology of adult community-acquired pneumonia in Asia: a systematic review. Trans R Soc Trop Med Hyg. 2014; 108(6): 326-37.

Lupisan S, Suzuki A, Macalalad N, et al. Etiology and epidemiology of community-acquired pneumonia in adults requiring hospital admission: A prospective study in rural Central Philippines. Int J Infect Dis. 2019; 80: 46-53.

Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk Susceptibility Tests. 13th ed. CLSI standard M02. (ISBN 1-56238-834-7 [Print]; ISBN 1-56238-835-5 [Electronic]). https://clsi.org/media/1925/m02ed13_sample.pdf.

The European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters. Version 9.0, 2019. http://www.eucast.org.

Magiorakos AP, Srinivasan A, Carey RB, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012; 18(3): 268-81.

Mandell LA. Community-acquired pneumonia: An overview. Postgrad Med. 2015; 127(6): 607-15.

Waterer GW. Community-acquired Pneumonia: A Global Perspective. Semin Respir Crit Care Med. 2016; 37(6): 799-805.

Stets R, Popescu M, Gonong JR, et al. Omadacycline for Community-Acquired Bacterial Pneumonia. N Engl J Med. 2019; 380(6): 517-27.

File TM JR, Rewerska B, Vucinic-Mihailovic V, et al. SOLITAIRE-IV: A Randomized, Double-Blind, Multicenter Study Comparing the Efficacy and Safety of Intravenous-to-Oral Solithromycin to Intravenous-to-Oral Moxifloxacin for Treatment of Community-Acquired Bacterial Pneumonia. Clin Infect Dis. 2016; 63(8): 1007-16.

Horcajada JP, Salata RA, Álvarez-Sala R, et al; DEFINE-CABP Study Group. A Phase 3 Study to Compare Delafloxacin With Moxifloxacin for the Treatment of Adults With Community-Acquired Bacterial Pneumonia (DEFINE-CABP). Open Forum Infect Dis. 2019; 7(1): ofz514.

Woodhead M. Community-acquired pneumonia in Europe: causative pathogens and resistance patterns. Eur Respir J Suppl. 2002; 36: 20s-27s.

Echaniz-Aviles G, Garza-González E, Román-Mancha AL, et al. Clinical and microbiological characteristics of community-acquired pneumonia associated with Streptococcus pneumoniae in adult patients in Mexico. Rev Argent Microbiol. 2019; 51(3): 234-40.

Toda H, Tanaka Y, Satoh K, et al. Epidemiological and molecular characterization of invasive Streptococcus pneumoniae isolated following introduction of 7-valent conjugate vaccine in Kinki region, Japan, 2008-2013. J Infect Chemother. 2020; 26(5): 451-8.

Kim SH, Chung DR, Song JH, et al.; Asian Network for Surveillance of Resistant Pathogens (ANSORP). Changes in serotype distribution and antimicrobial resistance of Streptococcus pneumoniae isolates from adult patients in Asia: Emergence of drug-resistant non-vaccine serotypes. Vaccine. 2020; 38(38): 6065-73.

Zhanel GG, Adam HJ. Introduction to the SAVE study (2011-15): Streptococcus pneumoniae serotyping and antimicrobial susceptibility: Assessment for Vaccine Efficacy in Canada after the introduction of PCV-13. J Antimicrob Chemother. 2018; 73(suppl_7): vii2-vii4.

Karlowsky JA, Adam HJ, Golden AR, et al.; Canadian Antimicrobial Resistance Alliance (CARA). Antimicrobial susceptibility testing of invasive isolates of Streptococcus pneumoniae from Canadian patients: the SAVE study, 2011-15. J Antimicrob Chemother. 2018; 73(suppl_7): vii5-vii11.

Aliberti S, Cook GS, Babu BL, et al.; GLIMP investigators. International prevalence and risk factors evaluation for drug-resistant Streptococcus pneumoniae pneumonia. J Infect. 2019; 79(4): 300-11.

Torumkuney D, Zemlickova H, Maruscak M, Morrissey I. Results from the Survey of Antibiotic Resistance (SOAR) 2014-16 in the Czech Republic. J Antimicrob Chemother. 2018; 73(suppl_5): v22-v27.

Zhang Y, Zhang F, Wang H, et al. Antimicrobial susceptibility of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolated from community-acquired respiratory tract infections in China: Results from the CARTIPS Antimicrobial Surveillance Program. J Glob Antimicrob Resist. 2016; 5: 36-41.

Shiu J, Ting G, Kiang TK. Clinical Pharmacokinetics and Pharmacodynamics of Delafloxacin. Eur J Drug Metab Pharmacokinet. 2019; 44(3): 305-17.

Ocheretyaner ER, Park TE. Delafloxacin: a novel fluoroquinolone with activity against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Expert Rev Anti Infect Ther. 2018; 16(7): 523-30.

Sun H, Chen L, Chen X, et al. [Antimicrobial susceptibility of community-acquired respiratory tract pathogens isolated from class B hospitals in China during 2013 and 2014]. Zhonghua Jie He He Hu Xi Za Zhi. 2016; 39(1): 30-7.

El-Sokkary RH, Ramadan RA, El-Shabrawy M, et al. Community acquired pneumonia among adult patients at an Egyptian university hospital: bacterial etiology, susceptibility profile and evaluation of the response to initial empiric antibiotic therapy. Infect Drug Resist. 2018; 11: 2141-50.

Pfaller MA, Mendes RE, Castanheira M, Flamm RK, Jones RN, Sader HS. Ceftaroline Activity Tested Against Bacterial Isolates Causing Community-acquired Respiratory Tract Infections and Skin and Skin Structure Infections in Pediatric Patients From United States Hospitals: 2012-2014. Pediatr Infect Dis J. 2017; 36(5): 486-91.

Hyun M, Noh CI, Ryu SY, Kim HA. Changing trends in clinical characteristics and antibiotic susceptibility of Klebsiella pneumoniae bacteremia. Korean J Intern Med. 2018; 33(3): 595-603.

Najjuka CF, Kateete DP, Kajumbula HM, Joloba ML, Essack SY. Antimicrobial susceptibility profiles of Escherichia coli and Klebsiella pneumoniae isolated from outpatients in urban and rural districts of Uganda. BMC Res Notes. 2016; 9: 235.

Marchese A, Ardito F, Fadda G, et al. The Sentinel Project: an update on the prevalence of antimicrobial resistance in community-acquired respiratory Streptococcus pneumoniae and Haemophilus spp. in Italy. Int J Antimicrob Agents. 2005; 26(1): 8-12.

Kosikowska U, Andrzejczuk S, Grywalska E, et al. Prevalence of susceptibility patterns of opportunistic bacteria in line with CLSI or EUCAST among Haemophilus parainfluenzae isolated from respiratory microbiota. Sci Rep. 2020; 10(1): 11512.

Cao B, Qu JX, Yin YD, Eldere JV. Overview of antimicrobial options for Mycoplasma pneumoniae pneumonia: focus on macrolide resistance. Clin Respir J. 2017; 11(4): 419-29.

Wang X, Zhang H, Zhang T, et al. Etiology of Community-Acquired Pneumonia Requiring Hospital Admission in Adults with and Without Cancers: A Single-Center Retrospective Study in China. Infect Drug Resist. 2020; 13: 1607-17.

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: 2335-41.

Arfaatabar M, Aminharati F, Azimi G, et al. High frequency of Mycoplasma pneumoniae among patients with atypical pneumonia in Tehran, Iran. Germs. 2018; 8(3): 126-33.

Carrim M, Wolter N, Benitez AJ, et al. Epidemiology and Molecular Identification and Characterization of Mycoplasma pneumoniae, South Africa, 2012-2015. Emerg Infect Dis. 2018; 24(3): 506-13.

Raeven VM, Spoorenberg SM, Boersma WG, et al.; Alkmaar study group; Ovidius study group. Atypical aetiology in patients hospitalised with community-acquired pneumonia is associated with age, gender and season; a data-analysis on four Dutch cohorts. BMC Infect Dis. 2016; 16: 299.

Aguilera-Alonso D, López Ruiz R, Centeno Rubiano J, et al. Características clínicas y epidemiológicas de las neumonías adquiridas en la comunidad por Mycoplasma pneumoniae en una población española, 2010-2015 [Epidemiological and clinical analysis of community-acquired Mycoplasma pneumonia in children from a Spanish population, 2010-2015]. An Pediatr (Engl Ed). 2019; 91(1): 21-9.

Yin YD, Wang R, Zhuo C, et al. Macrolide-resistant Mycoplasma pneumoniae prevalence and clinical aspects in adult patients with community-acquired pneumonia in China: a prospective multicenter surveillance study. J Thorac Dis. 2017; 9(10): 3774-81.

Bondeelle L, Bergeron A, Wolff M. Place des nouveaux antibiotiques dans le traitement de la pneumonie aiguë communautaire de l’adulte [The role of new antibiotics in the treatment of acute adult community acquired pneumonia]. Rev Mal Respir. 2019; 36(1): 104-17.

Kollef MH, Betthauser KD. New antibiotics for community-acquired pneumonia. Curr Opin Infect Dis. 2019; 32(2): 169-75.

Hopkins TM, Juang P, Weaver K, Kollef MH, Betthauser KD. Outcomes of Macrolide Deescalation in Severe Community-acquired Pneumonia. Clin Ther. 2019; 41(12): 2540-8.

McCurdy S, Keedy K, Lawrence L, et al. Efficacy of Delafloxacin versus Moxifloxacin against Bacterial Respiratory Pathogens in Adults with Community-Acquired Bacterial Pneumonia (CABP): Microbiology Results from the Delafloxacin Phase 3 CABP Trial. Antimicrob Agents Chemother. 2020; 64(3): e01949-19.

Hipp M, Burckhardt I. In vitro activity of newer antimicrobials against penicillin non-susceptible strains of Streptococcus pneumoniae. Infect Drug Resist. 2019; 12: 1889-93.