A problemática de Pseudomonas aeruginosa dentro de uma indústria farmacêutica: uma revisão integrativa da literatura
Palavras-chave:
Pseudomonas aeruginosa, Biofilme, Controle microbiológico, Indústria farmacêutica, Desinfecção
Resumo
A presença de Pseudomonas aeruginosa em ambientes produtivos representa um dos principais desafios de controle microbiológico na indústria farmacêutica, devido ao seu potencial patogênico e à formação de biofilme. Este estudo teve como objetivo analisar os desafios do isolamento de P. aeruginosa na indústria farmacêutica, com ênfase em sua persistência ambiental, formação de biofilme, resistência a desinfetantes e desafios na identificação. Trata-se de uma revisão integrativa realizada a partir das bases de dados PubMed e SciELO, complementada por compêndios e regulamentações da Anvisa. Os resultados demonstraram escassez de estudos com cepas industriais, comparado à literatura clínica, evidenciando lacunas que dificultam o controle microbiológico em ambientes produtivos. Nos estudos analisados (n=19) observou-se que em sistemas de água e armazenamento, P. aeruginosa encontra condições favoráveis para se estabelecer e formar biofilme. A capacidade de formação de biofilme favorece a persistência bacteriana podendo reduzir a eficácia de desinfetantes. Compostos como hipoclorito de sódio a 0,01% e quaternário de amônia a 0,05% mostraram maior eficácia, embora determinadas linhagens tenham demonstrado tolerância persistente (30%). Métodos semiautomatizados baseados em perfis fenotípicos/proteômicos (como o sistema VITEK®2 e MALDI TOF MS®) mostraram limitações frente a cepas ambientais da indústria, reforçando a importância do uso de técnicas moleculares, como o sequenciamento do gene 16S rRNA, para identificação acurada. Conclui-se que P. aeruginosa representa um importante desafio sanitário e operacional para a indústria farmacêutica, exigindo atualização tecnológica, vigilância microbiológica contínua e fortalecimento das estratégias de prevenção e controle de biofilmes.Referências
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BRASIL. Agência Nacional de Vigilância Sanitária. Resolução da Diretoria Colegiada - RDC nº 658, de 30 de março de 2022. Dispõe sobre as Diretrizes Gerais de Boas Práticas de Fabricação de Medicamentos. Diário Oficial da União, Brasília, DF, 1 abr. 2022.
BRASIL. Agência Nacional de Vigilância Sanitária. Farmacopeia Brasileira. 7. ed. Brasília, DF: ANVISA, 2024a. v. 1.
BRASIL. Agência Nacional de Vigilância Sanitária. Resolução da Diretoria Colegiada - RDC nº 940, de 14 de novembro de 2024. Dispõe sobre a aprovação da 7ª edição da Farmacopeia Brasileira. Brasília, DF: ANVISA, 2024b.
CALDEIRA, NGS et al. Characterization by MALDI-TOF MS and 16S rRNA Gene Sequencing of Aerobic Endospore-Forming Bacteria Isolated from Pharmaceutical Facility in Rio de Janeiro, Brazil. Microorganisms, v. 12, n. 4, ref. 724, p. 1-17, abr. 2024. Disponível em: https://doi.org/10.3390/microorganisms12040724.
CENGİZ, G; ALGIN YAPAR, E. Method decision for determining specific microorganisms in pharmaceutical products: An overview. Universal Journal of Pharmaceutical Research, v. 5, n. 5, p. 85-91, 2020. Disponível em: https://doi.org/10.22270/ujpr.v5i5.492.
COSTA, LV et al. Assessment of VITEK®2, MALDI-TOF MS and full gene 16S rRNA sequencing for aerobic endospore-forming bacteria isolated from a pharmaceutical facility. Journal of Microbiological Methods, v. 194, art. 106419, p. 1-5, 2022. Disponível em: https://doi.org/10.1016/j.mimet.2022.106419.
COSTA, AS et al. Standardization of an Effective Disinfection Methodology Against Microorganisms Isolated from a Pharmaceutical Industry Facility as a Contamination Control Strategy. Standards, v. 6, n. 2, p. 22, 2026. Disponível em: https://doi.org/10.3390/standards6020022
CROXATTO, A; PROD'HOM, G; GREUB, G. Applications of MALDI-TOF mass spectrometry in clinical diagnostic microbiology. FEMS Microbiology Reviews, v. 36, n. 2, p. 380–407, 2012. Disponível em: https://doi.org/10.1111/j.1574-6976.2011.00298.x.
EUROPEAN MEDICINES AGENCY (EMA). The Rules Governing Medicinal Products in the European Union. Volume 4: European Union Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use. Annex 1: Manufacture of Sterile Medicinal Products. Bruxelas, 2022.
HAIDAR, A et al. Biofilm formation and antibiotic resistance in Pseudomonas aeruginosa. The Microbe, v. 3, art. 100078, p. 1-9, 2024. Disponível em: https://doi.org/10.1016/j.microb.2024.100078.
JIMENEZ, L et al. Microbial Landscape of Pharmaceutical Failures: A 21-Year Review of FDA Enforcement Reports. BioTech, v. 15, n. 1, art. 8, p. 1-12, 2026. Disponível em: https://doi.org/10.3390/biotech15010008.
LETIZIA, M; DIGGLE, SP; WHITELEY, M. Pseudomonas aeruginosa: ecology, evolution, pathogenesis and antimicrobial susceptibility. Nat Rev Microbiol, v. 23, n. 11, p. 701-717, 2025. Disponível em: https://doi.org/10.1038/s41579-025-01193-8.
LI, Q et al. Leveraging whole-genome sequencing for microbial contamination tracking and risk assessment in pharmaceutical manufacturing. Front Microbiol, v. 17, p. 1807989, 2026.
LUZ, IS et al. Assessment of the microbiological quality of natural mineral waters according to the manufacturing time of 20 L returnable packs in Brazil. FEMS Microbiol Lett, v. 367, n. 15, p. fnaa120, 2020. Disponível em: https://doi.org/10.1093/femsle/fnaa120.
MAIA, AA et al. Resistência antimicrobiana de Pseudomonas aeruginosa isolados de pescado e de cortes e de miúdos de frango. Ciência e Tecnologia de Alimentos, v. 29, n. 1, p. 114-119, jan./mar. 2009. Disponível em: https://doi.org/10.1590/S0101-20612009000100018.
MASS Spectrometry MALDI-TOF Technology Species Level Identification. [S. l.]: BioMérieux, [2026]. Disponível em: https://www.biomerieux.com/corp/en/education/resource-hub/pharma-quality-control/scientific-library/mass-spectrometry-maldi-tof-species-level-identification.html. Acesso em: 9 maio 2026.
MATTOSO, JMV et al. Quantitative and qualitative evaluation of microorganism profile identified in bioburden analysis in a biopharmaceutical facility in Brazil: Criteria for classification and management of results. PDA J Pharm Sci Technol, v. 79, n. 2, p. 125-156, 2025. Disponível em: https://doi.org/10.5731/pdajpst.2023.012883.
MENA, KD; GERBA, CP. Risk assessment of Pseudomonas aeruginosa in water. Rev Environ Contam Toxicol, v. 201, p. 71-115, 2009. Disponível em: https://doi.org/10.1007/978-1-4419-0032-6_3.
PARENTERAL DRUG ASSOCIATION (PDA). Bioburden and Biofilm Management in Pharmaceutical Manufacturing Operations. Technical Report No. 69, 2015a.
PARENTERAL DRUG ASSOCIATION (PDA). Fundamentals of Cleaning and Disinfection Programs for Aseptic Manufacturing Facilities. Technical Report No. 70, 2015b.
RAMOS, JN et al. Challenges in the identification of environmental bacterial isolates from a pharmaceutical industry facility by 16S rRNA gene sequences. DNA, v. 5, n. 3, p. 33, 2025. Disponível em: https://doi.org/10.3390/dna5030033.
RATAJCZAK, M et al. Antibiotic Resistance, Biofilm Formation, and Presence of Genes Encoding Virulence Factors in Strains Isolated from the Pharmaceutical Production Environment. Pathogens. 2021. Disponível em: doi: 10.3390/pathogens10020130.
RUSSELL, AD Mechanisms of antimicrobial action of antiseptics and disinfectants: an increasingly important area of investigation. Journal of Antimicrobial Chemotherapy, v. 49, n. 4, p. 597-599, 2002. Disponível em: https://doi.org/10.1093/jac/49.4.597.
SAHU, A et al. Biofilm-dispersal patterns in ESKAPE pathogens. Arch Microbiol, v. 207, n. 9, p. 194, 2025. https://doi.org/10.1007/s00203-025-04394-0.
SELIM, NA; SAEED, AM; IBRAHIM, MK. Monitoring and controlling bacteria in pharmaceutical industries water system, Journal of Applied Microbiology, Volume 129, Issue 4, 1 October 2020. Disponível em: https://doi.org/10.1111/jam.14686
SOUZA, P.A. de et al. Evaluation of Antimicrobial Resistance Patterns of Pseudomonas aeruginosa Strains Isolated among COVID-19 Patients in Brazil Typed by Fourier-Transform Infrared Spectroscopy. Life, v. 14, n. 9, art. 1079, p. 1-15, 2024. Disponível em: https://doi.org/10.3390/life14091079.
SOUZA, P.A. de et al. Application and Limitations of 16S rRNA Gene Sequencing for Identifying WHO Priority Pathogenic Gram-Negative Bacilli. Infect Drug Resist, v. 18, p. 6353-6375, 2025b. Disponível em: https://doi.org/10.2147/IDR.S550704.
STAMATOSKI, B et al. Optimized genotyping method for identification of bacterial contaminants in pharmaceutical industry. Acta Pharm. 2016 Jun. Disponível em: https://doi.org/10.1515/acph-2016-0011
SILVA, BS et al. Growth kinetics modeling of Pseudomonas aeruginosa in natural mineral water. Int J Food Microbiol, v. 445, p. 111495, 2026. Disponível em: https://doi.org/10.1016/j.ijfoodmicro.2025.111495.
SONG, M et al. A comprehensive technology strategy for microbial identification and contamination investigation in the sterile drug manufacturing facility - A case study. Frontiers in Microbiology, v. 15, p. 1327175, 2024.
VASCONCELLOS, L et al. Phenotypical and Molecular Characterization of Pseudomonas spp. Isolated from a Pharmaceutical Facility. Processes, v. 14, art. 231, p. 1-16, 2026. Disponível em: https://doi.org/10.3390/pr14020231.
VASCONCELLOS, L et al. Caracterização molecular e avaliação da formação e tolerância a biocida do biofilme de Pseudomonas aeruginosa isoladas de águas minerais naturais. Revista Científica do UBM, v. 23, n. 44, p. 193-205, 2021. Disponível em: https://revista.ubm.br/index.php/revistacientifica/article/view/878
WEISER, R et al. Not all Pseudomonas aeruginosa are equal: strains from industrial sources possess uniquely large multireplicon genomes. Microbial Genomics, v. 5, n. 11, art. 000276, p. 1-13, 2019. Disponível em: https://doi.org/10.1099/mgen.0.000276.
WORLD HEALTH ORGANIZATION. WHO Bacterial Priority Pathogens List, 2024: bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance. Geneva: World Health Organization, 2024.
YANG, F et al. Comparative Genomic Analysis of Pseudomonas aeruginosa Isolates from Community-Acquired and Hospital-Acquired Pneumonia. Infection and Drug Resistance, v. 19, p. 4761-4777, 2026. Disponível em: https://doi.org/10.2147/IDR.S443567.
ZARAGOZA, R et al. Update of the treatment of nosocomial pneumonia in the ICU. Critical Care, v. 24, n. 1, art. 383, p. 1-11, 2020. Disponível em: https://doi.org/10.1186/s13054-020-03084-2
BATISTA, AMSC et al. Phenotypical characterization of Pseudomonas aeruginosa strains isolated from an immunobiological pharmaceutical industry facility. In: International Symposium On Immunobiological, 10., 2026. Rio de Janeiro. Annals... Rio de Janeiro: Bio-Manguinhos, 2026. p. 118. Disponível em: https://doi.org/10.35259/isi.2026_76200
BIOMÉRIEUX. Manual do VITEK® 2. [S. l.]: BioMérieux, [2026]. Disponível em: https://www.biomerieux.com/us/en/our-offer/clinical-products/vitek-2.html. Acesso em: 9 maio 2026.
BRASIL. Agência Nacional de Vigilância Sanitária. Resolução da Diretoria Colegiada - RDC nº 658, de 30 de março de 2022. Dispõe sobre as Diretrizes Gerais de Boas Práticas de Fabricação de Medicamentos. Diário Oficial da União, Brasília, DF, 1 abr. 2022.
BRASIL. Agência Nacional de Vigilância Sanitária. Farmacopeia Brasileira. 7. ed. Brasília, DF: ANVISA, 2024a. v. 1.
BRASIL. Agência Nacional de Vigilância Sanitária. Resolução da Diretoria Colegiada - RDC nº 940, de 14 de novembro de 2024. Dispõe sobre a aprovação da 7ª edição da Farmacopeia Brasileira. Brasília, DF: ANVISA, 2024b.
CALDEIRA, NGS et al. Characterization by MALDI-TOF MS and 16S rRNA Gene Sequencing of Aerobic Endospore-Forming Bacteria Isolated from Pharmaceutical Facility in Rio de Janeiro, Brazil. Microorganisms, v. 12, n. 4, ref. 724, p. 1-17, abr. 2024. Disponível em: https://doi.org/10.3390/microorganisms12040724.
CENGİZ, G; ALGIN YAPAR, E. Method decision for determining specific microorganisms in pharmaceutical products: An overview. Universal Journal of Pharmaceutical Research, v. 5, n. 5, p. 85-91, 2020. Disponível em: https://doi.org/10.22270/ujpr.v5i5.492.
COSTA, LV et al. Assessment of VITEK®2, MALDI-TOF MS and full gene 16S rRNA sequencing for aerobic endospore-forming bacteria isolated from a pharmaceutical facility. Journal of Microbiological Methods, v. 194, art. 106419, p. 1-5, 2022. Disponível em: https://doi.org/10.1016/j.mimet.2022.106419.
COSTA, AS et al. Standardization of an Effective Disinfection Methodology Against Microorganisms Isolated from a Pharmaceutical Industry Facility as a Contamination Control Strategy. Standards, v. 6, n. 2, p. 22, 2026. Disponível em: https://doi.org/10.3390/standards6020022
CROXATTO, A; PROD'HOM, G; GREUB, G. Applications of MALDI-TOF mass spectrometry in clinical diagnostic microbiology. FEMS Microbiology Reviews, v. 36, n. 2, p. 380–407, 2012. Disponível em: https://doi.org/10.1111/j.1574-6976.2011.00298.x.
EUROPEAN MEDICINES AGENCY (EMA). The Rules Governing Medicinal Products in the European Union. Volume 4: European Union Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use. Annex 1: Manufacture of Sterile Medicinal Products. Bruxelas, 2022.
HAIDAR, A et al. Biofilm formation and antibiotic resistance in Pseudomonas aeruginosa. The Microbe, v. 3, art. 100078, p. 1-9, 2024. Disponível em: https://doi.org/10.1016/j.microb.2024.100078.
JIMENEZ, L et al. Microbial Landscape of Pharmaceutical Failures: A 21-Year Review of FDA Enforcement Reports. BioTech, v. 15, n. 1, art. 8, p. 1-12, 2026. Disponível em: https://doi.org/10.3390/biotech15010008.
LETIZIA, M; DIGGLE, SP; WHITELEY, M. Pseudomonas aeruginosa: ecology, evolution, pathogenesis and antimicrobial susceptibility. Nat Rev Microbiol, v. 23, n. 11, p. 701-717, 2025. Disponível em: https://doi.org/10.1038/s41579-025-01193-8.
LI, Q et al. Leveraging whole-genome sequencing for microbial contamination tracking and risk assessment in pharmaceutical manufacturing. Front Microbiol, v. 17, p. 1807989, 2026.
LUZ, IS et al. Assessment of the microbiological quality of natural mineral waters according to the manufacturing time of 20 L returnable packs in Brazil. FEMS Microbiol Lett, v. 367, n. 15, p. fnaa120, 2020. Disponível em: https://doi.org/10.1093/femsle/fnaa120.
MAIA, AA et al. Resistência antimicrobiana de Pseudomonas aeruginosa isolados de pescado e de cortes e de miúdos de frango. Ciência e Tecnologia de Alimentos, v. 29, n. 1, p. 114-119, jan./mar. 2009. Disponível em: https://doi.org/10.1590/S0101-20612009000100018.
MASS Spectrometry MALDI-TOF Technology Species Level Identification. [S. l.]: BioMérieux, [2026]. Disponível em: https://www.biomerieux.com/corp/en/education/resource-hub/pharma-quality-control/scientific-library/mass-spectrometry-maldi-tof-species-level-identification.html. Acesso em: 9 maio 2026.
MATTOSO, JMV et al. Quantitative and qualitative evaluation of microorganism profile identified in bioburden analysis in a biopharmaceutical facility in Brazil: Criteria for classification and management of results. PDA J Pharm Sci Technol, v. 79, n. 2, p. 125-156, 2025. Disponível em: https://doi.org/10.5731/pdajpst.2023.012883.
MENA, KD; GERBA, CP. Risk assessment of Pseudomonas aeruginosa in water. Rev Environ Contam Toxicol, v. 201, p. 71-115, 2009. Disponível em: https://doi.org/10.1007/978-1-4419-0032-6_3.
PARENTERAL DRUG ASSOCIATION (PDA). Bioburden and Biofilm Management in Pharmaceutical Manufacturing Operations. Technical Report No. 69, 2015a.
PARENTERAL DRUG ASSOCIATION (PDA). Fundamentals of Cleaning and Disinfection Programs for Aseptic Manufacturing Facilities. Technical Report No. 70, 2015b.
RAMOS, JN et al. Challenges in the identification of environmental bacterial isolates from a pharmaceutical industry facility by 16S rRNA gene sequences. DNA, v. 5, n. 3, p. 33, 2025. Disponível em: https://doi.org/10.3390/dna5030033.
RATAJCZAK, M et al. Antibiotic Resistance, Biofilm Formation, and Presence of Genes Encoding Virulence Factors in Strains Isolated from the Pharmaceutical Production Environment. Pathogens. 2021. Disponível em: doi: 10.3390/pathogens10020130.
RUSSELL, AD Mechanisms of antimicrobial action of antiseptics and disinfectants: an increasingly important area of investigation. Journal of Antimicrobial Chemotherapy, v. 49, n. 4, p. 597-599, 2002. Disponível em: https://doi.org/10.1093/jac/49.4.597.
SAHU, A et al. Biofilm-dispersal patterns in ESKAPE pathogens. Arch Microbiol, v. 207, n. 9, p. 194, 2025. https://doi.org/10.1007/s00203-025-04394-0.
SELIM, NA; SAEED, AM; IBRAHIM, MK. Monitoring and controlling bacteria in pharmaceutical industries water system, Journal of Applied Microbiology, Volume 129, Issue 4, 1 October 2020. Disponível em: https://doi.org/10.1111/jam.14686
SOUZA, P.A. de et al. Evaluation of Antimicrobial Resistance Patterns of Pseudomonas aeruginosa Strains Isolated among COVID-19 Patients in Brazil Typed by Fourier-Transform Infrared Spectroscopy. Life, v. 14, n. 9, art. 1079, p. 1-15, 2024. Disponível em: https://doi.org/10.3390/life14091079.
SOUZA, P.A. de et al. Application and Limitations of 16S rRNA Gene Sequencing for Identifying WHO Priority Pathogenic Gram-Negative Bacilli. Infect Drug Resist, v. 18, p. 6353-6375, 2025b. Disponível em: https://doi.org/10.2147/IDR.S550704.
STAMATOSKI, B et al. Optimized genotyping method for identification of bacterial contaminants in pharmaceutical industry. Acta Pharm. 2016 Jun. Disponível em: https://doi.org/10.1515/acph-2016-0011
SILVA, BS et al. Growth kinetics modeling of Pseudomonas aeruginosa in natural mineral water. Int J Food Microbiol, v. 445, p. 111495, 2026. Disponível em: https://doi.org/10.1016/j.ijfoodmicro.2025.111495.
SONG, M et al. A comprehensive technology strategy for microbial identification and contamination investigation in the sterile drug manufacturing facility - A case study. Frontiers in Microbiology, v. 15, p. 1327175, 2024.
VASCONCELLOS, L et al. Phenotypical and Molecular Characterization of Pseudomonas spp. Isolated from a Pharmaceutical Facility. Processes, v. 14, art. 231, p. 1-16, 2026. Disponível em: https://doi.org/10.3390/pr14020231.
VASCONCELLOS, L et al. Caracterização molecular e avaliação da formação e tolerância a biocida do biofilme de Pseudomonas aeruginosa isoladas de águas minerais naturais. Revista Científica do UBM, v. 23, n. 44, p. 193-205, 2021. Disponível em: https://revista.ubm.br/index.php/revistacientifica/article/view/878
WEISER, R et al. Not all Pseudomonas aeruginosa are equal: strains from industrial sources possess uniquely large multireplicon genomes. Microbial Genomics, v. 5, n. 11, art. 000276, p. 1-13, 2019. Disponível em: https://doi.org/10.1099/mgen.0.000276.
WORLD HEALTH ORGANIZATION. WHO Bacterial Priority Pathogens List, 2024: bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance. Geneva: World Health Organization, 2024.
YANG, F et al. Comparative Genomic Analysis of Pseudomonas aeruginosa Isolates from Community-Acquired and Hospital-Acquired Pneumonia. Infection and Drug Resistance, v. 19, p. 4761-4777, 2026. Disponível em: https://doi.org/10.2147/IDR.S443567.
ZARAGOZA, R et al. Update of the treatment of nosocomial pneumonia in the ICU. Critical Care, v. 24, n. 1, art. 383, p. 1-11, 2020. Disponível em: https://doi.org/10.1186/s13054-020-03084-2
Publicado
2026-08-22
Como Citar
BATISTA, A. M. S. C.; COSTA, L. V. DA; BRANDÃO, M. L. L.; VASCONCELLOS, L. A problemática de Pseudomonas aeruginosa dentro de uma indústria farmacêutica: uma revisão integrativa da literatura. Revista Científica do UBM, v. 28, n. 55, p. 188-206, 22 ago. 2026.
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