Abstract
Objectives
Providencia infections are rare but emerging clinical entities with limited published evidence. We performed a pooled descriptive analysis by extracting data from case reports and case series to elucidate the clinical characteristics, outcomes, and potential predictors of adverse events.
Methods
A total of 69 cases of Providencia infection were analyzed (mean age: 52.77 ± 21.04 years; 61.19% male). Descriptive statistics were used to summarize patient demographics, clinical characteristics, and infection types. Complete-case data were used for regression analyses specifically, 63 cases for the sepsis outcome, 64 cases for urinary tract infections (UTIs), 62 cases for tracheal aspirates (TAs), and 46 cases for mortality. Logistic regression models with cluster-robust standard errors were applied to account for intra-study dependencies. Variables were selected for multivariable modeling using a backward stepwise approach with a p-value threshold of ≤ 0.3.
Results
The overall in-hospital mortality was 20.0% (13/69). The predominant infection types were bloodstream infections (sepsis) in 21 cases (30.43%), UTIs in 18 cases (26.09%), and surgical site infections in 17 cases (24.64%). In multivariable regression analysis, the experience of shock during hospitalization emerged as a significant predictor of poor outcome; patients who experienced shock had an adjusted odds ratio of 5.57 (95% confidence interval: 1.26–24.61, p = 0.023) for adverse events. Other factors, such as gender, underlying comorbidities, and various antibiotic administrations (e.g., cephalosporine, beta-lactam, carbapenem), were not independently associated with the outcomes in the final models. Notable exploratory signals: shock→mortality; cephalosporins→UTI; fluoroquinolones→SSI; longer antibiotic duration→lower TA positivity (all imprecise).
Conclusions
Our pooled descriptive analysis of Providencia infections reveals an overall mortality rate of 20.0% and identifies shock during hospitalization as an independent predictor of adverse outcomes. Because the evidence is derived from heterogeneous case reports and small case series with substantial missing data, all adjusted estimates are imprecise and should be considered hypothesis‑generating; they must not be used to guide clinical practice without confirmation in prospective studies.
Clinical trial number
Not applicable.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12879-026-13068-1.
Keywords: Anti-bacterial agents, Providencia, Drug resistance, Bacterial, Tracheal diseases, Urinary tract infections
Introduction
Antimicrobial resistance (AMR) poses a critical global health threat, directly causing an estimated 1.3 million deaths in 2019 [1]. Intensive care units (ICUs) are particularly vulnerable, with over half of patients developing infections; the rising prevalence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) gram-negative bacteria in these settings increases mortality, morbidity, and healthcare costs [2, 3].
Providencia species are gram-negative, urease-producing Enterobacterales (including P. stuartii, P. rettgeri, P. alcalifaciens, P. rustigianii, and P. heimbachae) that have emerged as opportunistic pathogens in hospitalized and long-term care populations; P. rettgeri and P. stuartii are most frequently implicated in catheter-associated urinary infections, particularly among elderly patients with long-term urinary catheters [4]. These organisms are present in environmental reservoirs (water, soil, animals) and can colonize healthcare environments, facilitating sporadic transmission and occasional small outbreaks in wards with high device use [4, 5].
Clinical manifestations of Providencia infection vary from uncomplicated catheter-associated urinary tract infections to invasive extra-urinary disease such as wound infections, pneumonia, neonatal sepsis, and bacteremia; mortality for Providencia bacteremia can be substantial in older or comorbid patients [4, 5]. Treatment is increasingly challenging because isolates often display resistance to multiple antibiotic classes, with documented emergence of extended-spectrum beta-lactamase (ESBL) and carbapenemase producers, and intrinsic or acquired reduced susceptibility to agents such as aminopenicillins, first-generation cephalosporins, polymyxins, and tigecycline in some reports [5].
Current knowledge is fragmented and largely derived from case reports and small series, creating heterogeneous reporting of resistance definitions, incomplete microbiologic characterization (for example, limited routine carbapenemase or molecular testing), and variable documentation of timing and indications for antibiotic exposures [6]. This evidence base limits firm conclusions about incidence, attributable mortality, optimal empiric regimens, and the causal role of prior antibiotic exposure or devices in adverse outcomes. Nevertheless, accumulating case evidence suggests MDR/XDR Providencia may be an emerging clinical concern in specific high-risk populations, notably critically ill, catheterized, or neurologically impaired patients [7, 8].
To address these gaps, we performed a pooled descriptive analysis of published case reports and case series to summarize clinical presentations, resistance patterns, management approaches, and signals of adverse outcomes [9]. Recognizing the limitations of source data and inconsistent MDR terminology, we broadened inclusion criteria to capture documented antimicrobial resistance across studies (MDR and XDR) and framed all pooled findings as exploratory and hypothesis-generating [10, 11]. Our aim is to provide clinicians and infection-prevention teams with a clearer synthesis of current signals, to inform local empiric decision-making and stewardship, and to define priorities for prospective, standardized research.
Material & method
Protocol
This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines [12]. The protocol for this study has been registered in the PROSPERO database with the code CRD42024599419 (Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024599419).
Sources
A systematic search of PubMed (http://pubmed.ncbi.nlm.nih.gov), Web of Science(https://clarivate.com), Scopus (http://www.scopus.com) and Google Scholar (https://scholar.google.com) was performed up to June 2024 for English full‑text case reports and small case series of confirmed Providencia infection. Included reports had to state: (a) infection site; (b) predisposing factors/underlying disease; (c) diagnostic method(s); (d) antibiotic or other treatments; and (e) case outcomes. Extracted antibiotic data reflect overall administration because empiric versus targeted use was not consistently reported. The search strategy is shown in Table 1 and the screening flow in Fig. 1 [13].
Table 1.
Search Strategy
| Database | Search Terms | Search Date | Last Update | Result |
|---|---|---|---|---|
| PubMed | “Providencia“[Mesh] | 2024/06/22 | 2024/07/23 | 67 |
| Scopus | (TITLE-ABS-KEY (“Providencia”)) AND (case AND report) AND (LIMIT-TO (DOCTYPE, “ar”)) AND (LIMIT-TO (LANGUAGE, “English”)) AND (LIMIT-TO (EXACTKEYWORD, “Case Report”)) | 2024/06/23 | 2024/07/23 | 116 |
| Web of science | TS=(Providencia) AND all field= (Case report OR report case) | 2024/06/25 | 2024/07/23 | 66 |
| Google scholar | “ Providencia” AND " Case report” Anywhere in the article | 2024/07/01 | 2024/07/24 | 5940 |
Fig. 1.
PRISMA flow diagram of study inclusion process
Eligibility criteria
Studies reporting individual patient‑level data for confirmed Providencia infections with evidence of antimicrobial resistance were included; aggregated‑only reports, reviews, letters, conference abstracts, book chapters, and commentaries were excluded. Cases without an explicit ‘MDR’ label were included when antimicrobial resistance or related characteristics were reported.
Data collection
Titles/abstracts were screened independently by two reviewers; disagreements were resolved by discussion or a third reviewer. Duplicates were removed and screening was managed in EndNote® 20. Extracted variables included presentation, age, sex, year, country, comorbidities, diagnosis, antibiotic treatment, and outcome.
Review of the quality of extracted articles (Risk of bias in individual studies)
The ROBINS‑I tool (Risk of Bias in Non‑randomized Studies of Interventions) was considered at the protocol stage for assessing risk of bias. However, because ROBINS‑I is designed for non‑randomized comparative studies and the included evidence consisted predominantly of heterogeneous case reports and small case series, its direct application was not feasible. Therefore, we performed a structured descriptive appraisal of reporting and methodological features reported in each article. Six domains were assessed: (1) study type and patient selection; (2) diagnostic confirmation and microbiological reporting; (3) completeness of clinical outcome reporting and follow‑up; (4) treatment reporting (agent, dose, route, duration, empiric vs. targeted); (5) reporting of potential confounders and co‑interventions; and (6) funding and conflict‑of‑interest disclosure. Each domain was rated as Complete, Partial, or Absent by two independent reviewers, with disagreements resolved by discussion. Per‑study ratings are provided in Supplementary Table S1. These assessments informed sensitivity checks that excluded reports with Absent ratings in key domains [14, 15].
Definitions
The standardized criteria for multidrug‑resistant (MDR) and extensively drug‑resistant (XDR) isolates described by Magiorakos et al. were adopted for the purpose of this study. Specifically, MDR isolates were defined as those demonstrating non‑susceptibility to at least one agent in three or more antimicrobial categories, whereas XDR isolates were defined as those exhibiting non‑susceptibility to all agents except for one or two antimicrobial categories. When explicit MDR/XDR/PDR labels or sufficiently complete susceptibility panels were provided in the original reports, Magiorakos criteria were applied; in the absence of such labels or panels, agent‑level susceptibility results were recorded as reported and no post‑hoc reclassification was performed [16]. Full regression outputs and sensitivity analysis details are provided in Supplementary Table S2.
Statistical analysis
All available case‑level data were recorded; analyses used complete‑case data for each outcome (Sepsis n = 63; UTI n = 64; TA n = 62; Mortality n = 46). Descriptive statistics were used to summarize patient characteristics. To identify factors associated with clinical outcomes, we performed exploratory multivariable logistic regression models with cluster‑robust standard errors to account for within‑study correlation. The primary outcome variables for these models were: (1) in-hospital mortality (2), presence of sepsis (3), urinary tract infection (UTI) (4), surgical site infection (SSI), and (5) pathogen isolation from tracheal aspirates (TA). Variable selection for each model was performed using backward stepwise selection with a liberal entry and retention threshold of p ≤ 0.30 to identify potential signals given the exploratory nature of the study. Pre‑specified sensitivity analyses were conducted and 95% confidence intervals (CIs) are reported for all estimates.
Continuous variables are presented as mean ± SD or median (IQR); categorical variables as counts and percentages; Fisher’s exact test was used for group comparisons. Analyses were two‑tailed with α < 0.05 and were performed in STATA v17. Adjusted estimates with wide CIs are presented as hypothesis‑generating and interpreted with caution.
Results
In this study, data from 69 cases of Providencia infection were analyzed (Table 2). Overall, the mean age of the patients was 52.77 ± 21.04 years that 61.19% of cases were male. The most common underlying diseases among these patients were neurological or psychiatric disorders (22.39%), hypertension (21.74%), and diabetes (20.29%). The most prevalent signs and symptoms during hospitalization included fever (29.71%), pain (22.06%), and shock (21.74%) (Table 3). Key findings are summarized below; full regression tables and sensitivity analyses are presented in Supplementary Table S2 to improve readability.
Table 2.
Study Characteristics (PICOTS Framework)
| No | First Author Name | Article Name | Journal | Country | Year | No. of Patients | Type |
|---|---|---|---|---|---|---|---|
| 1 | Walter E | “Spontaneous perforation of the common bile duct: report of a case” | The Australian and New Zealand Journal of Surgery | Australia | 1978 | 1 | Case Report |
| 2 | Keren G | “Gram-negative septicemia caused by Providencia stuartii” | The International Journal of Pediatric Nephrology | Israel | 1987 | 1 | Case Report |
| 3 | V Pinto | “Two cases of fatal transfusion-associated bacterial sepsis provoked by Providencia rettgeri” | Haematologica | 1999 | 1 | Case Report | |
| 4 | Laurent Poirel | “Multidrug-resistant Providencia stuartii expressing extended-spectrum β-lactamase PER-1 originating in Kosovo” | Italy | Switzerland | 2008 | 1 | Case Report |
| 5 | S. Sabtcheva1 | “Plasmid-mediated per-1 extended-spectrum betalactamase in Providencia rettgeri from Bulgaria” | The Journal of Antimicrobial Chemotherapy | Bulgaria | 2008 | 1 | Case Report |
| 6 | V. Miriagou | “Providencia stuartii with VIM-1 metallo-beta-lactamase” | Journal of Antimicrobial Chemotherapy | Greece | 2009 | 1 | Case Report |
| 7 | Jorge Manuel Marull | “Automatic implantable cardioverter defibrillator pocket infection due to Providencia rettgeri: a Case Report” | Cases Journal | United States | 2009 | 1 | Case Report |
| 8 | Oguz Resat Sipahi | “Meningitis Due to Providencia stuartii” | Journal of Clinical Microbiology | Turkey | 2010 | 1 | Case Report |
| 9 | Caterina Simon | “Images in cardiovascular medicine. Bacterial pericarditis due to Providencia stuartii: an atypical case of relapsing pericarditis” | Circulation | Italy | 2010 | 1 | Case Report |
| 10 | CY Cheong | “A Rare Infection Following Snakebite” | Malaysian Orthopedic Journal | Malaysia | 2010 | 1 | Case Report |
| 11 | Hyun-Jung Cho | “A Case of Providencia rettgeri Sepsis in a Patient with Cervical Cord Injury” | Infection and Chemotherapy | Korea | 2010 | 1 | Case Report |
| 12 | Carmine Franco Muccio | “Pyogenic abscess from Providencia stuartii mimicking necrotic tumour at perfusion-weighted imaging” | Neurological Science | Italy | 2011 | 1 | Case Report |
| 13 | Gilho Lee | “Xanthogranulomatous pyelonephritis with nephrocutaneous fistula due to Providencia rettgeri infection” | Journal of Medical Microbiology | Korea | 2011 | 1 | Case Report |
| 14 | S Unverdi | “Peritonitis Due to Providencia stuartii” | Peritoneal Dialysis International | Turkey | 2011 | 1 | Case Report |
| 15 | Ayhan Tekiner | “Nosocomial Providencia stuartii Meningitis: A Case Report” | Journal of Neurology Research | Turkey | 2011 | 1 | Case Report |
| 16 | Kayoko Hayakawa | “Growing prevalence of Providencia stuartii associated with the increased use of colistin at a tertiary health care center” | International Journal of Infectious Diseases | United States | 2012 | 1 | Case Report |
| 17 | Sihem Mahrouki | “First characterization of a Providencia stuartii clinical isolate from a Tunisian intensive care unit coproducing VEB-1-a, OXA-2, qnrA6 and aac(6 ‘)-Ib-cr determinants” | The Brazilian Journal of Infectious Diseases | Tunis | 2013 | 1 | Case Report |
| 18 | Ana Paula D’Alincourt Carvalho-Assef | “Isolation of NDM-producing Providencia rettgeri in Brazil” | Journal of Antimicrobial Chemotherapy | Brazil | 2013 | 1 | Case Report |
| 19 | Robin R Chamberland | “Renal abscess caused by a Providencia stuartii isolate biochemically misidentified as Pasteurella” | Journal of Clinical Microbiology | United States | 2013 | 1 | Case Report |
| 20 | Ahmed Al Montasir | “Purple Urine Bag Syndrome” | Journal of Family Medicine and Primary Care | Bangladesh | 2013 | 1 | Case Report |
| 21 | Tanmoy Kumar Maiti | “Providencia rettgeri: An unusual cause of central nervous system infections” | The American Journal of the Medical Sciences | India | 2013 | 3 | Case Series |
| 22 | Tom Kai Ming Wang | “Providencia rettgeri Peritonitis in a Patient on Peritoneal Dialysis with Perforated Appendicitis” | Peritoneal Dialysis International | New Zealand | 2014 | 1 | Case Report |
| 23 | Sung Kuk Hong | “Spontaneous Bacterial Peritonitis with Septicemia with Providencia rettgeri and Clostridium perfringens” | Annals of Clinical Microbiology | Korea | 2014 | 1 | Case Report |
| 24 | Michael A Washington | “A Case of Wound Infection with Providencia rettgeri and Coincident Gout in a Patient from Guam” | Hawai’i Journal of Medicine & Public Health | Guam | 2015 | 1 | Case Report |
| 25 | Nelson Vieira do Carmo Junior | “First report of a NDM-producing Providencia rettgeri strain in the state of São Paulo” | The Brazilian Journal of Infectious Diseases | Brazil | 2015 | 1 | Case Report |
| 26 | Edoardo Virgilio | “Invasive Infection of Post-Surgical Esophagocutaneous Fistula Due to Providencia stuartii” | Surgical Infections | Italy | 2015 | 1 | Case Report |
| 27 | B A Lipsky | “Managing Urinary Tract Infections in Men” | Hospital Practice | United States | 2015 | 1 | Case Report |
| 28 | Wilson Kwong | “Providencia rettgeri: an unexpected case of Gram-negative cellulitis” | Wounds International | Canada | 2015 | 1 | Case Report |
| 29 | Evangelia Douka | “Emergence of a pandrug-resistant VIM-1-producing Providencia stuartii clonal strain causing an outbreak in a Greek intensive care unit” | International Journal of Antimicrobial Agents | Greece | 2015 | 1 | Case Report |
| 30 | Ranjit Sah | “Detection of pan drug resistance OXA-48 producing Providencia in an ICU patient for the first time in Nepal” | Second National Summit of Health and Population Scientists in Nepal | Nepal | 2016 | 1 | Case Report |
| 31 | Caio A M Aires | “Selection of KPC-2-producing Providencia stuartii during treatment for septicemia” | Diagnostic Microbiology and Infectious Disease | Brazil | 2016 | 1 | Case Report |
| 32 | Elliot S. Crane | “Case Report: Providencia stuartii conjunctivitis” | Journal of Ophthalmic Inflammation and Infection | United States | 2016 | 1 | Case Report |
| 33 | V S Tshisevhe | “Outbreak of carbapenem-resistant Providencia rettgeri in a tertiary hospital” | South African Medical Journal | South Africa | 2016 | 4 | Case Series |
| 34 | Shaista Bin-Ti Nazir | “PROVIDENCIA RETTGERI: AN UNEXPECTED CAUSE OF SEPSIS” | International Journal of Advanced Research | India | 2017 | 1 | Case Report |
| 35 | Kyawzaw Lin | “Recurrent Primary Suprahepatic Abscess Due to Providencia Stuartii: A Rare Phenomenon” | Cureus | United States | 2017 | 1 | Case Report |
| 36 | Deepak Sharma | “First Case Report of Providencia Rettgeri neonatal sepsis” | BMC Research Notes | India | 2017 | 1 | Case Report |
| 37 | Siddharth Sagar | “Providencia rettgeri: An emerging nosocomial uropathogen in an indwelling urinary catheterised patient” | Journal of Clinical and Diagnostic Research | India | 2017 | 1 | Case Report |
| 38 | Sonia Yaqub | “Purple Urine Bag Syndrome: A Case Report and Review of the Literature” | Indian Journal of Nephrology | India | 2017 | 1 | Case Report |
| 39 | Won Choi | “A case of bilateral keratitis caused by Providencia alcalifaciens: a rarely encountered ocular pathogen” | International Ophthalmology | South Korea | 2018 | 1 | Case Report |
| 40 | M. Abdallah | “First report of carbapenem-resistant Providencia stuartii in Saudi Arabia” | New Microbes and New Infections | Saudi Arabia | 2018 | 1 | Case Report |
| 41 | Ting-Ying Lee | “Refractory urinary tract infection complicated rectus sheath abscess: A Case Report” | Urology Case Reports | ROC | 2018 | 1 | Case Report |
| 42 | Lopes Juliana | “Providencia stuartii aortic prosthetic valve endocarditis with formation of paravalvular pseudoaneurysm” | Medical Case Reports | Portugal | 2018 | 1 | Case Report |
| 43 | Maria Livia Burzo | “The strange case of congenital mitral stenosis in an adult man with cor triatriatum” | Echocardiography | Italy | 2019 | 1 | Case Report |
| 44 | Elisabeth A George | “Providencia stuartii septic vasculitis” | JAAD Case Reports | Rhode Island | 2020 | 1 | Case Report |
| 45 | MKE Ogbac | “Community Acquired Pneumonia Secondary to Multiple Drug-Resistant Providencia Stuartii: A Case Report” | American Journal of Respiratory and Critical Care Medicine | Philippines | 2020 | 1 | Case Report |
| 46 | Elham Pourheidar | “Description of an effective treatment regimen for ventilator-associated pneumonia due to pandrug-resistant Providencia: a Case Report” | Pneumologia | Iran | 2020 | 1 | Case Report |
| 47 | Zhunan Xu | “Xanthogranulomatous pyelonephritis infected with the Providencia stuartii: a Case Report and literature review” | BMC Nephrology | China | 2021 | 1 | Case Report |
| 48 | Patrick Mc Gann | “Pan-drug resistant Providencia rettgeri contributing to a fatal case of COVID-19” | Journal of Medical Microbiology | United States | 2021 | 1 | Case Report |
| 49 | Nupur B Patel | “Ventilator-associated pneumonia due to carbapenem-resistant Providencia rettgeri” | BMJ Case Reports | India | 2021 | 1 | Case Report |
| 50 | Priya Patel | “Visually Striking and Alarming Phenomenon – Case Report of Purple Urine Bag Syndrome” | Frontiers in Medical Case Reports | Florida | 2021 | 1 | Case Report |
| 51 | Jenny Lin | “Chronic canaliculitis with canaliculoliths due to Providencia stuartii infection” | Orbit | United States | 2021 | 1 | Case Report |
| 52 | Shabal Sapkota | “Providencia rettgeri infection complicating cranial surgery: illustrative cases” | Journal of Neurosurgery: Case Lessons | Nepal | 2021 | 2 | Case Series |
| 53 | Yu Zhao | “Case Report: Cryptogenic giant brain abscess caused by Providencia rettgeri mimicking stroke and tumor in a patient with impaired immunity” | Frontiers in Neurology | China | 2022 | 1 | Case Report |
| 54 | Mallorie L Huff | “Providencia rettgeri Infection Compromising Post-Burn Recovery: A Lesson in the Importance of Follow-Up Care” | Cureus | United States | 2022 | 1 | Case Report |
| 55 | Niloofar Rezaie | “Isolation of MDR Providencia stuartii from tracheal aspirates of two hospitalized patients” | Health Biotechnology and Biopharma | Iran | 2022 | 2 | Case Series |
| 56 | Amparo Hoard | “Genomic Analysis of two NDM 1 Providencia stuartii Strains Recovered from a Single Patient” | Current Microbiology | United States/Argentina | 2022 | 1 | Case Report |
| 57 | Joseph Allen White | “Providencia alcalifaciens in a patient with a staghorn calculus: a novel presentation” | Diagnostic Microbiology and Infectious Disease | Cuba | 2023 | 1 | Case Report |
| 58 | Je Yeon Byeon | “A CARE-compliant article: A Case Report of unusual eschar and extensive soft tissue necrosis in Tsutsugamushi disease” | Medicine | South Korea | 2023 | 1 | Case Report |
| 59 | Joseph Allen White | “Providencia alcalifaciens in a patient with a staghorn calculus: a novel presentation” | Diagnostic Microbiology and Infectious Disease | Cuba | 2023 | 1 | Case Report |
| 60 | Diogo Casal | “An unexpected infection in a venous leg ulcer: a Case Report” | Wounds International | Brazil | 2023 | 1 | Case Report |
| 61 | Wajiha Khan | “Providencia Rettgeri Meningitis” | International Journal of Clinical Studies & Medical Case Reports | Pakistan | 2024 | 1 | Case Report |
| 62 | Fangfei Yan | “Hepatic failure with Providencia rettgeri infection: Case Report” | Preprint | China | 2024 | 1 | Case Report |
Table 3.
General and clinical characteristics of patients
| Factors | Total cases (n = 69) |
|---|---|
| Age (years) | 52.77 ± 21.04 |
| Gender | |
| Female | 26 (38.81) |
| Male | 41 (61.19) |
| Medical history (Yes) | |
| Hypertension | 15 (21.74) |
| Diabetes | 14 (20.29) |
| Hyperlipidemia | 2 (2.90) |
| Cardiovascular diseases | 6 (8.70) |
| Chronic kidney disease | 11 (15.94) |
| Neurological/Physiological disorders | 15 (22.39) |
| Chronic respiratory diseases | 10 (14.49) |
| Urinary tract infection | 13 (19.12) |
| Immune suppressive disease | 6 (8.70) |
| Kidney stone | 2 (2.90) |
| Signs and symptoms (Yes) | |
| Pain | 15 (22.06) |
| Fever | 27 (29.71) |
| Chill | 6 (8.70) |
| Lethargy | 8 (11.76) |
| Diarrhea | 2 (2.90) |
| Shock | 15 (21.74) |
| Abscess | 5 (7.35) |
| Wound | 9 (13.64) |
| Discharge | 11 (17.19) |
| Hematuria | 3 (4.35) |
| Dysuria | 4 (5.80) |
| Ophthalmic complications | 4 (5.80) |
| Nausea or vomiting | 5 (7.25) |
| Bleeding | 5 (7.25) |
| Gastrointestinal complications | 4 (5.88) |
| Liver dysfunction | 3 (4.35) |
Data presented as mean ± standard deviation or frequency and percentage
The detection of the pathogen was predominantly carried out using conventional biochemical methods or automated systems, as reported in the majority of the included studies. In a smaller subset of studies, these methods were complemented by molecular diagnostic techniques, such as polymerase chain reaction (PCR) or sequencing, to confirm the identification. It should be noted that many case reports and series did not provide detailed information on the detection methodology, reflecting the inherent heterogeneity in reporting practices across the available literature.
According to the results in Table 2, the most common types of Providencia reported were 53.13% P. rettgeri, 40.63% P. stuartii, and 6.25% P. alcalifaciens. The most frequently used antibiotic treatment for these patients included Cephalosporin and Carbapenem (36.23%), Beta-lactam (27.54%), and Aminoglycoside and Fluoroquinolone (24.64%). It should be noted that these percentages represent overall antibiotic use as reported in the original studies, without differentiating between empiric and targeted therapy. The median duration of antibiotic use during hospitalization was 14 days, with an interquartile range of 10 to 24.5 days (Table 4).
Table 4.
Patients’ medication and clinical characteristics
| Factors | Total cases (n = 69) |
|---|---|
| Medication during hospitalization (Yes) | |
| Cephalosporine | 25 (36.23) |
| Penicillin | 9 (13.04) |
| Beta-lactam | 19 (27.54) |
| Carbapenem | 25 (36.23) |
| Vancomycin | 9 (13.04) |
| Aminoglycoside | 17 (24.64) |
| Fluoroquinolone | 17 (24.64) |
| Clindamycin | 2 (2.90) |
| Teicoplanin | 1 (1.45) |
| Cotrimoxazole | 4 (5.80) |
| Colistin | 5 (7.25) |
| Linezolid | 2 (2.90) |
| Macrolide | 1 (1.45) |
| Polymyxins | 2 (2.90) |
| Chloramphenicol | 2 (2.90) |
| Fosfomycin | 1 (1.45) |
| Duration of antibiotic intake (days) | 14 (10–24.5) |
| Follow-up duration (days) | 26.5 (14–51) |
| Providencia type | |
| P. alcalifaciens | 4 (6.25) |
| P. stuartii | 26 (40.63) |
| P. rettgeri | 34 (53.13) |
| Infection types | |
| Blood infections (Sepsis) | 21 (30.43) |
| Urinary tract infections (UTIs) | 18 (26.09) |
| Surgical site infections (SSIs) | 17 (24.64) |
| Tracheal aspirates (TAs) | 10 (14.49) |
| Central nervous system infections | 6 (8.70) |
| Abscesses | 2 (2.90) |
| Peritonitis | 2 (2.90) |
| Other | 2 (2.90) |
| Vital status | |
| Alive | 52 (80.0) |
| Died | 13 (20.0) |
| Discharged | |
| No | 15 (22.73) |
| Yes | 51 (77.27) |
Data presented as median and interquartile range (Q1-Q3) or frequency and percentageNote 1: The antibiotic administration data represent overall usage as extracted from the source studies and do not distinguish between empiric therapy and targeted therapy due to inconsistent reporting.Note 2: Overall antibiotic use is reported without distinguishing empiric versus targeted therapy; some intrinsically resistant agents may have been used in combinations
The most common infections reported during hospitalization were sepsis (30.43%), urinary tract infections (26.09%), and surgical site infections (24.64%). Ultimately, 20% of the cases (n = 13) died in the hospital (Table 3). Details about the characteristics of patients are presented in Tables 3 and 4.
According to the results in Table 4, after examining and comparing the number of days of antibiotic use and clinical outcomes by type of Providencia, it was observed that the median duration of antibiotic use in the P. alcalifaciens was higher than that in the other species, although this difference was not statistically significant (P = 0.908).
On the other hand, among patients with sepsis (57.14%), surgical site infections (57.14%), and central nervous system infections (66.67%), P. rettgeri accounted for more infections. Also, in patients with urinary tract infections (60%), tracheal aspirates (70%), and abscesses (100%), the most common Providencia species was P. stuartii. This difference in distribution was not statistically significant (P > 0.05). In addition, among the deceased patients, P. rettgeri (54.55%) and P. stuartii (45.45%) were more common, while no deaths were reported among individuals infected with P. alcalifaciens (P = 1.000) (Table 5).
Table 5.
Comparison of clinical events between Providencia types
| Factors |
P. alcalifaciens (n = 4, 6.25%) |
P. stuartii (n = 26, 40.63%) |
P. rettgeri (n = 34, 53.13%) |
P_value |
|---|---|---|---|---|
| Duration of antibiotic intake (days) | 16 (3–21) | 14 (10–28) | 14 (14–21) | 0.908 |
| Infection types | ||||
| Blood infections (Sepsis) | 1 (7.14) | 5 (35.71) | 13 (57.14) | 0.271 |
| Urinary tract infections (UTIs) | 1 (6.67) | 9 (60.0) | 5 (33.33) | 0.153 |
| Surgical site infections (SSIs) | 1 (7.14) | 5 (35.71) | 8 (57.14) | 0.896 |
| Tracheal aspirates (TAs) | 1 (10.0) | 7 (70.0) | 2 (20.0) | 0.052 |
| Central nervous system infections | 0 (0.0) | 2 (33.33) | 4 (66.67) | 0.792 |
| Abscesses | 0 (0.0) | 2 (100.0) | 0 (0.0) | 0.283 |
| Peritonitis | 0 (0.0) | 1 (50.0) | 1 (50.0) | 1.000 |
| Other | 0 (0.0) | 0 (0.0) | 2 (100.0) | 0.562 |
| Vital status | ||||
| Alive | 4 (8.0) | 20 (40.0) | 26 (52.0) | 1.000 |
| Died | 0 (0.0) | 5 (45.45) | 6 (54.55) | |
| Discharged | ||||
| No | 0 (0.0) | 5 (38.46) | 8 (61.54) | 0.705 |
| Yes | 4 (8.16) | 20 (40.82) | 25 (51.02) | |
Data presented as median and interquartile range (Q1-Q3) or frequency and percentagePercentages estimated in row
According to the results in Supplementary Table S2, based on the univariate analysis, a statistically significant association was observed only between Fluoroquinolone use and the occurrence of sepsis (P = 0.033). However, after considering the effects of other probable confounding variables based on multivariable analysis, no statistically significant association was found between any variables, particularly the type of Providencia species, and the occurrence of sepsis (P > 0.05) (Supplementary Table S2).
The results of the multivariable logistic regression model examining the factors associated with urinary tract infections (UTIs) indicated that, after considering probable influencing variables, only Cephalosporin use was significantly associated with the occurrence of UTIs (P = 0.020). Specifically, cases who had Cephalosporin included in their treatment regimen during hospitalization had 5.15 times the odds of developing UTIs compared to those who did not receive this medication (OR = 5.15, 95% CI = 1.29–20.52) (Supplementary Table S2). The adjusted estimate is imprecise and should be considered hypothesis-generating rather than definitive.
Regarding surgical site infections (SSIs), the univariate analysis showed that the only influencing variable in this study was Fluoroquinolone use (P = 0.016). After considering probable influencing variables on SSIs, the results remained similar to the univariate analysis. Specifically, individuals who had Fluoroquinolone included in their treatment regimen during hospitalization had 5.04 times the odds of developing SSIs compared to those who did not receive this medication (OR = 5.04, 95% CI = 1.28–19.71, P = 0.020) (Supplementary Table S2). The adjusted estimate is imprecise and should be considered hypothesis-generating rather than definitive.
With respect to tracheal aspirates (TAs), it was observed in the univariate analysis that both the type of Providencia species identified and the duration of antibiotic use were significantly associated with the isolation of the pathogen from TA samples (P < 0.05). Based on the multivariable analysis, only the duration of antibiotic use remained significantly associated with pathogen isolation, with each additional day of antibiotic therapy reducing the odds by 20% (OR = 0.80, 95% CI = 0.67–0.95, P = 0.012). Although a higher likelihood of pathogen isolation was observed in cases involving P. stuartii compared to those with P. alcalifaciens and P. rettgeri, this association was not statistically significant (OR = 2.96, 95% CI = 0.51–17.16, P = 0.225) (Supplementary Table S2). The adjusted estimate is imprecise and should be considered hypothesis-generating rather than definitive.
Regarding in-hospital mortality, as shown in the results of Supplementary Table S2, the only associated factor on in-hospital mortality in this study was the shock as a sign and symptom during hospitalization (P = 0.018). Also, the results of multivariable analysis remained consistent with the univariate analysis. Specifically, individuals who experienced shock during their hospitalization had 5.57 times the odds of in-hospital mortality compared to those who did not experience shock (OR = 5.57, 95% CI = 1.26–24.61, P = 0.023) (Supplementary Table S2). These multivariable models for all adjusted odds ratio are exploratory; effect estimates should be considered hypothesis‑generating given sparse data and incomplete reporting.
Infectious presentations were dominated by sepsis (30.43%), urinary tract infections (26.09%), and surgical site infections (24.64%); overall in-hospital mortality was 20% (13/69). Common antibiotic classes used were cephalosporins and carbapenems (36.23%), beta-lactams (27.54%), and aminoglycosides and fluoroquinolones (24.64%). Exploratory adjusted analyses suggested shock was associated with higher in-hospital mortality (adjusted OR 5.57, 95% CI 1.26–24.61), but several adjusted estimates were imprecise; see Supplementary Table S2 for full models and sensitivity checks.
Key signals: shock was associated with higher in-hospital mortality (adjusted OR 5.57, 95% CI 1.26–24.61); cephalosporin exposure with higher odds of UTI (adjusted OR 5.15, 95% CI 1.29–20.52); fluoroquinolone exposure with higher odds of SSI (adjusted OR 5.04, 95% CI 1.28–19.71); longer antibiotic duration associated with lower odds of tracheal aspirate positivity (adjusted OR per day 0.80, 95% CI 0.67–0.95). All associations are exploratory and imprecise. An association between reported shock and mortality was observed in the pooled reports; however, given the small number of events, heterogeneity in reporting, and missing data, this finding should be interpreted as an observed association rather than evidence of causation.
Due to the substantial heterogeneity among the included studies, a formal risk-of-bias analysis using the ROBINS-I tool was deemed unfeasible. Instead, a descriptive appraisal of the methodological quality was conducted. Key study characteristics such as study design, patient selection, data collection methods, and outcome assessment were extracted and summarized. This descriptive analysis revealed considerable variability in the reporting quality across studies. Some articles provided comprehensive methodological details, while others lacked key information, underscoring potential areas of bias and highlighting methodological limitations. These findings offer preliminary insights into the overall quality of the evidence and help identify critical gaps that should be addressed in future research.
The structured appraisal revealed frequent reporting gaps (Supplementary Table S1). Diagnostic confirmation and full susceptibility data were Complete in 23/69 (33.3%) reports. Treatment reporting that included agent, dose, duration and whether therapy was empiric versus targeted was Complete in 19/69 (27.5%). Follow-up timing was Complete in 28/69 (40.6%). Funding/conflict statements were infrequent (8.69, 11.6%). Because missingness clustered in diagnostics, treatment details, and follow-up, we conducted pre-specified sensitivity analyses excluding reports with Absent key domains; these checks did not change the direction of the primary association (shock → in-hospital mortality) but reduced precision (Supplementary Table S1).
Discussion
Infections caused by extensively drug-resistant (XDR) Providencia represent a growing clinical concern because therapeutic options are frequently limited and evidence guiding management is sparse. In this systematic synthesis of 69 published case reports and small case series, several notable patterns emerged. The pooled cases were, on average, younger than cohorts reported in some prior surveillance studies (mean age 52.8 ± 21.0 years), and P. rettgeri accounted for the majority of reported isolates (53.1%), a distribution that contrasts with other series reporting P. stuartii predominance [4, 9, 17–21]. These apparent discrepancies likely reflect differences in geographic sampling, case ascertainment (hospital surveillance versus published case reports), local nosocomial ecology, and publication bias toward unusual or severe presentations, rather than a definitive global shift in species-level epidemiology.
The analyses presented here are exploratory and hypothesis‑generating: they synthesize heterogeneous case reports and small case series and include sensitivity analyses using synthetic data. These results are intended to inform future study design and hypothesis testing, not to establish causal relationships.
Clinical manifestations in the assembled reports were heterogeneous, with bloodstream infections (sepsis), urinary tract infections, and surgical-site infections predominating. The median duration of antibiotic therapy reported in these cases (14 days) exceeded durations described in some earlier series, a difference that may reflect case severity, treatment of complicated infections, or reporting bias toward prolonged or refractory courses. Importantly, the assembled evidence base is derived largely from case reports and small series that vary substantially in diagnostic methods, microbiologic characterization (including inconsistent reporting of ESBL and carbapenemase testing), and completeness of treatment and outcome data. These limitations constrain the ability to draw causal inferences or to generalize effect estimates to broader patient populations.
Our adjusted analyses identified several exploratory associations that merit cautious interpretation. The presence of shock during hospitalization was associated with substantially increased odds of in-hospital mortality (adjusted OR 5.57, 95% CI 1.26–24.61). Additional signals included associations of cephalosporin exposure with higher odds of urinary tract infection, fluoroquinolone exposure with higher odds of surgical-site infection, and an inverse association between antibiotic duration and tracheal aspirate positivity. Each of these findings is imprecise and potentially subject to confounding by indication, reverse causation, and reporting bias. For example, patients with greater illness severity are both more likely to receive broad-spectrum agents and to experience adverse outcomes, creating a bidirectional relationship between resistance, treatment intensity, and clinical deterioration that cannot be disentangled reliably in uncontrolled case reports. Accordingly, these associations should be regarded as hypothesis-generating signals that warrant confirmation in prospectively collected, systematically reported datasets.
The observed clustering of severe presentations among cases with multidrug resistance raises two non-mutually exclusive concerns. First, resistance phenotype may serve as a marker of greater clinical vulnerability: patients with prolonged hospitalization, invasive devices, or multiple prior antibiotic exposures are at increased risk both of acquiring resistant organisms and of poor outcomes. Second, resistance may contribute directly to adverse outcomes by delaying receipt of effective therapy. Both mechanisms underscore the clinical importance of rapid microbiologic diagnosis, timely susceptibility testing, and early involvement of infectious-disease specialists in the management of high-risk patients suspected to harbor resistant Providencia.
Therapeutic approaches reported across the assembled cases were heterogeneous and frequently empirical or combinatorial, often involving cephalosporins, carbapenems, aminoglycosides, and fluoroquinolones administered sequentially or concurrently. Inconsistent documentation of susceptibility results, molecular resistance mechanisms (ESBL, carbapenemase), dosing regimens, and timing of therapy relative to culture results precluded robust comparative-effectiveness assessments. Consequently, no definitive recommendations regarding optimal monotherapy versus combination therapy can be derived from the current evidence. The frequent reliance on multidrug regimens, however, highlights an urgent need for prospective registries or cohort studies that systematically capture treatment indications, regimen composition, microbiologic susceptibilities, dosing, and clinical outcomes to enable meaningful comparative analyses and to inform guideline development.
From an infection-prevention and stewardship perspective, several practical implications follow. Institutions should interpret species distributions and susceptibility patterns in the context of local surveillance data rather than extrapolating from case reports alone. Where XDR Providencia isolates are identified, prompt infection-control measures including isolation, reinforcement of contact precautions, targeted environmental cleaning, and consideration of molecular epidemiology to investigate transmission are warranted to limit nosocomial spread [5, 9, 22, 23]. Antimicrobial stewardship interventions that limit unnecessary exposure to broad-spectrum cephalosporins and fluoroquinolones, promote early de-escalation based on culture results, and ensure adherence to surgical prophylaxis guidelines may reduce selective pressure and the emergence of resistant strains [24].
Methodological limitations of the underlying literature and of our synthesis merit emphasis. Case reports and small series are inherently susceptible to selection and publication biases, often overrepresenting severe or atypical presentations. Reporting heterogeneity particularly incomplete or inconsistent documentation of diagnostic methods, susceptibility testing, antibiotic timing and intent (empiric versus targeted), and follow-up introduces substantial missingness and measurement error. These factors reduce statistical power, inflate uncertainty around adjusted estimates, and limit external validity. We therefore present adjusted associations as exploratory and interpret them with caution.
To advance understanding and to generate actionable evidence, future research should prioritize prospective, adequately powered studies and coordinated registry efforts that employ standardized case definitions, systematic microbiologic confirmation (including molecular characterization of resistance determinants), and rigorous, time-stamped documentation of antibiotic exposures (dose, duration, and empiric versus targeted intent). Analytical strategies that are robust to sparse and heterogeneous data such as penalized regression techniques, Bayesian hierarchical models, and pre-specified sensitivity analyses excluding reports with major reporting gaps should be considered to improve estimate stability and to identify reproducible associations.
An inverse association between antibiotic duration and tracheal-aspirate positivity was observed in multivariable analysis but requires cautious interpretation; this may reflect indication bias (longer courses for patients at higher aspiration risk), transient suppression or clearance of detectable colonization, or variability in sampling timing and technique. Standardized respiratory-sampling protocols and prospective recording of sampling relative to antibiotic exposure are needed to clarify causality [25].
Septic shock carried markedly increased risk of in-hospital death in adjusted analyses (≈ 5-fold), underscoring the need for early recognition, guideline-based resuscitation and organ support, timely source control, and rapid access to effective antimicrobials and diagnostics when Providencia infection is suspected [26].
Reported regimens were heterogeneous and often empirical or combinatorial (cephalosporins, carbapenems, β-lactams, aminoglycosides, fluoroquinolones), with inconsistent reporting of susceptibilities, molecular resistance mechanisms, dosing, and timing relative to cultures. These limitations preclude definitive comparative-effectiveness conclusions and highlight the need for prospective registries and cohort studies that systematically capture treatment, microbiology, and outcomes [27, 28].
Given the predominance of P. rettgeri in this series and longer antibiotic courses observed, institutions should reassess empiric policies against current local susceptibility data and strengthen device management and infection-prevention practices in high-risk wards (ICU, neurosurgery, long-term care) [29].
The findings generate testable hypotheses that require confirmation in prospective, standardized studies with time-stamped antibiotic data and robust analytic methods (penalized regression, Bayesian hierarchical models). Meanwhile, clinicians should rely on local surveillance and antibiograms, apply antimicrobial-stewardship principles, obtain appropriate cultures before therapy when feasible, and implement rapid infection-control measures for suspected MDR/XDR Providencia.
In summary, this synthesis of published case reports and small series highlights the clinical heterogeneity and management challenges posed by MDR/XDR Providencia infections, identifies several exploratory signals that warrant further investigation, and underscores the need for improved surveillance, standardized reporting, and prospective research to inform clinical practice and infection-control policy. Until higher-quality evidence is available, clinicians should rely on local antibiograms, apply antimicrobial stewardship principles, obtain appropriate cultures prior to therapy when feasible, involve infectious-disease specialists early for unstable or high-risk patients, and implement prompt infection-control measures when resistant isolates are detected.
Conclusion
In conclusion, while this study provides preliminary insights into the antimicrobial resistance patterns of Providencia infections, the inherent limitations associated with pooling data from case reports and case series including heterogeneity, selection bias, and reporting bias must be acknowledged. Consequently, our findings should be regarded as exploratory and hypothesis‑generating rather than as conclusive evidence for clinical practice. Prospective and controlled studies are required to confirm these preliminary associations and establish more robust conclusions.
Limitations
The evidence base for this study is limited to published case reports and small case series, which are inherently prone to publication, selection, and reporting biases and vary in data quality; this heterogeneity is further compounded by inconsistent case definitions, diagnostic criteria, and incomplete reporting of key variables such as detailed antibiogram classifications (MDR/XDR/PDR) and standardized temporal mortality endpoints (e.g., 15‑ or 30‑day mortality). Many important variables have high proportions of missing data, treatment regimens and critical details (dose, duration, follow‑up) are frequently omitted, and for several outcomes the number of events is small resulting in wide 95% confidence intervals, sparse covariate information, and limited capacity for reliable multivariable inference. Although we report an aggregated mortality estimate of 20%, this figure derives from pooled, non‑uniform reports rather than from robust, prospectively collected outcomes. Synthetic data were generated to facilitate exploratory analyses and scenario testing, but these data are based on assumptions and cannot substitute for prospectively collected observational or randomized data. We applied logistic regression with cluster‑robust standard errors and conducted sensitivity analyses (complete‑case and multiple imputation, and analyses with/without synthetic data) to mitigate some limitations; nevertheless, the adjusted estimates remain imprecise and should be regarded as hypothesis‑generating signals rather than evidence of causal or definitive clinical associations. Future multicenter prospective studies with standardized case definitions, uniform outcome measures, and comprehensive data collection are required to validate these preliminary observations and to better define optimal management strategies.
Supplementary Information
Below is the link to the electronic supplementary material.
Acknowledgements
Not applicable.
Author contributions
The authors’ contributions to the paper are as follows: study conception and design (S.H., S.A, H.E.); data collection and search (S.A., S.M.S.); analysis and interpretation of results (H.E., S.A., S.M.S.); draft manuscript preparation (S.A., S.M.S.). All authors (S.H., S.A, S.M.S, and H.E.) critically reviewed the results and approved the final version of the manuscript.
Funding
Authors received no financial support for this research.
Data availability
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
Since this is a systematic review and meta-analysis, ethical approval and consent are not required.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.