Review Article

Antibiotic Resistance in Providencia spp. in Iran: A Comprehensive Review of Patterns, Mechanisms, and Public Health Implications

Please cite this article as follows: Shabani S. Antibiotic resistance in Providencia spp. in Iran: a comprehensive review of patterns, mechanisms, and public health implications. Avicenna J Clin Microbiol Infect. 2025;12(1):43-46. doi:10.34172/ajcmi.3587

Introduction

The genus Providencia, a group of Gram-negative bacilli within the Enterobacteriaceae family, was first discovered by Rettger in 1904 and later formally named by Kauffmann in 1951. The species P. stuartii naturally inhabits environments such as soil, water, and sewage (1,2). The Providencia genus includes five distinct species, namely, P. stuartii, P. rettgeri, P. alcalifaciens, P. heimbachae, and P. rustigianii. These bacteria are typically found in human secretions, including urine, sputum, blood, stool, and wounds. P. rettgeri and P. stuartii are particularly significant as they are associated with infections such as urinary tract infections and can lead to bacteremia in immunocompromised individuals; they are infrequent opportunistic pathogens within the Enterobacteriaceae family (3). Their impact on human and animal health is noteworthy, often resulting in outbreaks of hospital-acquired infections. The rising prevalence of multidrug resistant (MDR) strains of P. rettgeri poses a considerable global public health threat. Although carbapenems have been extensively used for treating MDR bacterial infections, certain isolates of P. rettgeri have developed resistance to these critical antibiotics (4). The first case of carbapenem-resistant Providencia was reported in Japan in 2000. Since then, similar cases have emerged in various countries, including Nepal, Pakistan, Portugal, South Africa, South Korea, the United Kingdom, Afghanistan, Algeria, Argentina, Brazil, Bulgaria, Canada, China, Ecuador, Greece, India, Israel, Italy, Mexico, and the United States (5). This highlights the urgent need for ongoing monitoring of β-lactamase- and carbapenemase-producing strains of P. rettgeri in clinical settings.

In Iran, numerous studies have examined the resistance patterns of Enterobacteriaceae from a variety of samples. However, there is limited information regarding antimicrobial resistance specifically in Providencia. Two particular studies conducted in Tehran and Ardabil have provided partial insights into the antibiotic resistance patterns of Providencia within Enterobacteriaceae samples.

Methods

To achieve the study’s objectives, several databases, including Google,PubMed, and Scopus, were searched, in addition to performing a systematic review of clinical case reports, peer-reviewed articles, and surveillance studies to evaluate the antibiotic resistance profiles of Providencia in Iran. Different published studies (2000–2024) were included in this investigation, focusing on Providencia resistance to critical antibiotics, such as cephalosporins, carbapenems, fluoroquinolones, and the like. These antibiotics are MDR or pandrug resistance (PDR) Providencia based on CLSI performance guidelines for antimicrobial susceptibility testing. The obtained data were analyzed to determine prevalent resistance genes, mechanisms, and regional variations.

Discussion

The high prevalence of MDR Providencia in Iran underscores the need for immediate interventions, including stricter antimicrobial stewardship, enhanced surveillance systems, and molecular epidemiological studies to track resistance dynamics.

Providencia stuartii, first isolated by Rettger (1904) and formally named by Kauffmann (1951), is typically found in natural environments such as water, soil, and sewage (6). Its presence as a rare opportunistic pathogen within the Enterobacteriaceae family can lead to significant outbreaks of hospital-acquired infections. Despite extensive research on resistance patterns among Enterobacteriaceae in various Iranian medical centers, Providencia, being less common, has only been identified in two specific locations focused on Enterobacteriaceae. The first report of carbapenem-resistant Providencia emerged in Japan in 2000, with subsequent detections reported in other countries, including Nepal, Pakistan, Portugal, South Africa, South Korea, the United Kingdom, Afghanistan, Algeria, Argentina, Brazil, Bulgaria, Canada, China, Ecuador, Greece, India, Israel, Italy, Mexico, and the United States (5,7). The initial clinical isolates of P. rettgeri producing the IMP-1 metallo-β-lactamase (MBL) were documented in laboratory-based surveillance in western Japan during the same year (8). In 2008, Algeria reported the first clinical isolate of P. stuartii that produced the VIM-19 MBL (9). Evidence indicates that IMP-type MBL-producing isolates have been identified in Japan, South Korea, and the United States, while NDM-type MBL-producing isolates have emerged globally. Conversely, the majority of carbapenem-resistant P. stuartii isolates predominantly produce VIM-type MBLs, which are especially prevalent in Algeria and Greece (10). Notably, an NDM-type MBL-producing isolate of P. stuartii has been documented in Afghanistan (11,12). In recent years, there has been a concerning increase in reports of carbapenem-resistant P. stuartii and P. rettgeri isolates harboring the blaNDM gene. For instance, one report identified five clinical isolates of carbapenem-resistant P. rettgeri- and P. stuartii-producing IMP-type MBLs across three distinct hospitals in Japan. In Switzerland, P. stuartii isolates containing chromosomally encoded blaNDM-1 and blaOXA-48 carbapenemase genes were identified in wound samples from a patient transferred from Macedonia. Additionally, various isolates with carbapenemases, including KPC and VIM, have been documented in Greece, Argentina, Brazil, and Saudi Arabia (13-16). In Iran, while numerous studies have focused on the resistance patterns of Enterobacteriaceae from diverse samples, limited information exists regarding the antimicrobial resistance specific to Providencia. However, two studies—one in Tehran and the other in Ardabil—have provided insights into the resistance patterns of Providencia. In the study conducted in Ardabil, investigating antibiotic resistance patterns among enteric organisms in children, 305 fecal samples were collected between April and August 2017. Among them, three Providencia cases were identified, with 70% exhibiting MDR, and their resistance mechanisms did not involve AMPC/ESBL (17). Another study from Tehran University examined 11 157 urine samples, discovering that 9171 belonged to gram-negative bacteria, including six cases of Providencia, where 50% were found to be MDR. Table 1 provides details regarding the specific resistance profiles of these six isolates. Given the high rate of carbapenem resistance, this is likely substantiated by other studies conducted in Asia that have identified various carbapenemases, including VIM, IMP, NDM-1 MBL, OXA-48, and KPC, which underscores the urgent need for effective antimicrobial stewardship and surveillance strategies to combat the spread of these resistant pathogens. The increasing issues surrounding resistance in Providencia species, particularly P. stuartii, are drawing global attention. The emergence of carbapenem resistance and the production of MBLs have been reported worldwide. Various MBL variants (e.g., IMP-type and NDM-type) have surfaced in different regions, indicating a troubling trend in the evolution of resistance mechanisms and underscoring the need for continuous monitoring and targeted research (18).

Results

Although Providencia is a rare opportunistic pathogen among the Enterobacteriaceae and is infrequently isolated from human secretion samples, our findings demonstrated a concerning rise in antimicrobial resistance among Providencia isolates in Iran, with resistance to carbapenems and extended-spectrum beta-lactams frequently reported. Moreover, it was found that its antibiotic resistance patterns can complicate treatment. Emergency PDR Providencia is a critical health threat since it is intrinsically resistant to various commonly used antibiotics, including colistin, and tigecycline, which is utilized for some other MDR Enterobacteriaceae spp. Studies conducted in Iran indicate that between 50% and 70% of Providencia cases exhibit MDR or PDR with resistance mechanisms; this resistance is not solely attributable to extended-spectrum beta-lactamases (ESBLs) or AmpC beta-lactamases; given the high rate of carbapenem resistance observed, it is likely corroborated by other studies in Asia that have identified carbapenemases such as VIM, IMP, NDM-1 metallo-beta-lactamase (MBL), OXA-48, and KPC.

Regional studies highlight variability in resistance rates, probably reflecting variations in healthcare practices and antimicrobial stewardship.

Conclusion

The findings of this study are significant for guiding the appropriate prescription of antibiotics for infections caused by Providencia species.

The escalating antibiotic resistance in Providencia spp. within Iran presents a substantial challenge to public health due to their intrinsic resistance to some used antibiotics, such as colistin, and tigecycline, utilized for several other MDR Enterobacteriaceae spp., considering the possibility of the carbapenem resistance pattern, as in other studies in Asia, including carbapenemases (e.g., VIM, IMP, NDM-1 MBL, OXA 48, and KPC). Therefore, antibiotics such as aztreonam and ceftazidime-avibactam should be considered for MBL-type carbapenem-resistant Providencia species and OXA48 carbapenemase Providencia species, respectively.

Comprehensive strategies encompassing improved genetic and molecular studies of resistance patterns, diagnostics, rational antibiotic use, and robust monitoring are imperative to curb the spread of resistant strains.

Future research should prioritize the characterization of resistance determinants and the development of targeted therapeutic approaches.

Competing Interests

None.

Ethical Approval

Not applicable.

Funding

None.

References

1. Ovchinnikova OG, Rozalski A, Liu B, Knirel YA. O-antigens of bacteria of the genus Providencia: structure, serology, genetics, and biosynthesis. Biochemistry (Mosc) 2013; 78(7):798-817. doi: 10.1134/s0006297913070110 [Crossref] [ Google Scholar]
2. Lin K, Lin AN, Linn S, Reddy M, Bakshi A. Recurrent primary suprahepatic abscess due to Providencia stuartii: a rare phenomenon. Cureus 2017; 9(9):e1691. doi: 10.7759/cureus.1691 [Crossref] [ Google Scholar]
3. Mbelle NM, Osei Sekyere J, Amoako DG, Maningi NE, Modipane L, Essack SY. Genomic analysis of a multidrug-resistant clinical Providencia rettgeri (PR002) strain with the novel integron ln1483 and an A/C plasmid replicon. Ann N Y Acad Sci 2020; 1462(1):92-103. doi: 10.1111/nyas.14237 [Crossref] [ Google Scholar]
4. Munita JM, Arias CA. Mechanisms of antibiotic resistance. Microbiol Spectr 2016;4(2):10.1128/microbiolspec.VMBF-0016-2015. doi: 10.1128/microbiolspec.VMBF-0016-2015.
5. Li Y, Shao K, Cai R, Liu Y, Liu X, Ni F. Detection of NDM-1 and OXA-10 co-producing Providencia rettgeri clinical isolate. Infect Drug Resist 2023; 16:5319-28. doi: 10.2147/idr.S418131 [Crossref] [ Google Scholar]
6. Johnson AO, Forsyth V, Smith SN, Learman BS, Brauer AL, White AN. Transposon insertion site sequencing of Providencia stuartii: essential genes, fitness factors for catheter-associated urinary tract infection, and the impact of polymicrobial infection on fitness requirements. mSphere 2020; 5(3):e00412-20. doi: 10.1128/mSphere.00412-20 [Crossref] [ Google Scholar]
7. Nishio H, Komatsu M, Shibata N, Shimakawa K, Sueyoshi N, Ura T. Metallo-beta-lactamase-producing gram-negative bacilli: laboratory-based surveillance in cooperation with 13 clinical laboratories in the Kinki region of Japan. J Clin Microbiol 2004; 42(11):5256-63. doi: 10.1128/jcm.42.11.5256-5263.2004 [Crossref] [ Google Scholar]
8. Iwata S, Tada T, Hishinuma T, Tohya M, Oshiro S, Kuwahara-Arai K. Emergence of carbapenem-resistant Providencia rettgeri and Providencia stuartii producing IMP-type metallo-β-lactamase in Japan. Antimicrob Agents Chemother 2020; 64(11):e00382-20. doi: 10.1128/aac.00382-20 [Crossref] [ Google Scholar]
9. Robin F, Aggoune-Khinache N, Delmas J, Naim M, Bonnet R. Novel VIM metallo-beta-lactamase variant from clinical isolates of Enterobacteriaceae from Algeria. Antimicrob Agents Chemother 2010; 54(1):466-70. doi: 10.1128/aac.00017-09 [Crossref] [ Google Scholar]
10. Watanabe M, Iyobe S, Inoue M, Mitsuhashi S. Transferable imipenem resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother 1991; 35(1):147-51. doi: 10.1128/aac.35.1.147 [Crossref] [ Google Scholar]
11. McGann P, Hang J, Clifford RJ, Yang Y, Kwak YI, Kuschner RA. Complete sequence of a novel 178-kilobase plasmid carrying bla(NDM-1) in a Providencia stuartii strain isolated in Afghanistan. Antimicrob Agents Chemother 2012; 56(4):1673-9. doi: 10.1128/aac.05604-11 [Crossref] [ Google Scholar]
12. Manageiro V, Sampaio DA, Pereira P, Rodrigues P, Vieira L, Palos C. Draft genome sequence of the first NDM-1-producing Providencia stuartii strain isolated in Portugal. Genome Announc 2015; 3(5):e01077-15. doi: 10.1128/genomeA.01077-15 [Crossref] [ Google Scholar]
13. Douka E, Perivolioti E, Kraniotaki E, Fountoulis K, Economidou F, Tsakris A. Emergence of a pandrug-resistant VIM-1-producing Providencia stuartii clonal strain causing an outbreak in a Greek intensive care unit. Int J Antimicrob Agents 2015; 45(5):533-6. doi: 10.1016/j.ijantimicag.2014.12.030 [Crossref] [ Google Scholar]
14. Moser AI, Keller PM, Campos-Madueno EI, Poirel L, Nordmann P, Endimiani A. A patient with multiple carbapenemase producers including an unusual Citrobacter sedlakii hosting an IncC bla(NDM-1)- and armA-carrying plasmid. Pathog Immun 2021; 6(2):119-34. doi: 10.20411/pai.v6i2.482 [Crossref] [ Google Scholar]
15. Abdallah M, Alhababi R, Alqudah N, Aldyyat B, Alharthy A. First report of carbapenem-resistant Providencia stuartii in Saudi Arabia. New Microbes New Infect 2018; 26:107-9. doi: 10.1016/j.nmni.2018.09.007 [Crossref] [ Google Scholar]
16. Tavares CP, Pereira PS, de Andrade Marques E, Faria C Jr, da Penha Araújo Herkenhoff de Souza M, de Almeida R. Molecular epidemiology of KPC-2-producing Enterobacteriaceae (non-Klebsiella pneumoniae) isolated from Brazil. Diagn Microbiol Infect Dis 2015; 82(4):326-30. doi: 10.1016/j.diagmicrobio.2015.04.002 [Crossref] [ Google Scholar]
17. Habibzadeh N, Peeri Doghaheh H, Manouchehri Far M, Alimohammadi Asl H, Iranpour S, Arzanlou M. Fecal carriage of extended-spectrum β-lactamases and pAmpC producing Enterobacterales in an Iranian community: prevalence, risk factors, molecular epidemiology, and antibiotic resistance. Microb Drug Resist 2022; 28(9):921-34. doi: 10.1089/mdr.2021.0029 [Crossref] [ Google Scholar]
18. Jasemi S, Rahdar HA, Karami-Zarandi M, Mahfouzi S, Abdollahi A, Feizabadi MM. Anti-microbial resistance pattern of uropathogens isolated from hospitalized patients in Imam Khomeini hospital, Tehran, Iran. Arch Med Lab Sci 2011; 3(4):1-5. doi: 10.22037/amls.v3i4.21815 [Crossref] [ Google Scholar]
19. Rezaie N, Agghamohammad S, Rohani M, Javadi A, Badmasti F, Soltani Shirazi A. Isolation of MDR Providencia stuartii from tracheal aspirates of two hospitalized patients. Health Biotechnol Biopharma 2022; 6(3):73-9. doi: 10.22034/hbb.2022.24 [Crossref] [ Google Scholar]
20. Hadavand F, Naseri SR, Mardani M, Tabarsi P, Keyvanfar A, Gachkar L. An outbreak of pan-drug resistant Providencia species in an intensive care unit: a case-series. Arch Clin Infect Dis 2024; 19(3):e145826. doi: 10.5812/archcid-145826 [Crossref] [ Google Scholar]