Infectious Complications of Peripheral Intravenous Catheters and Their Hematogenous Distant Sequelae: A Systematic Review and Meta-Analysis

1. Introduction

Peripheral intravenous catheters (PIVCs) are by far the most frequently placed intravascular devices in clinical practice: approximately 2 billion PIVCs are inserted worldwide each year [1,2]. In the United States alone, more than 300 million PIVCs are placed annually, with prevalence studies documenting their presence in 70–90% of all hospitalized patients [3,4]. PIVCs are indispensable for drug administration, fluid therapy, blood product transfusion, and emergency vascular access; yet, despite their ubiquity, their infectious complications have received disproportionately little attention compared with central venous catheter (CVC)-related infections [5].

The clinical literature on catheter-associated bloodstream infections (CABSIs) has historically been dominated by central-line-associated bloodstream infection (CLABSI), a surveillance construct formally defined by the United States Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN) requiring the catheter tip to terminate in a central vessel—thereby explicitly excluding all peripheral vascular devices from the definition [6]. This exclusion has generated a systematic and widely documented surveillance gap: PIVC-related bloodstream infections (PIVC-BSIs) are invisible in national healthcare-associated infection reporting systems, their true incidence is unknown, and their downstream clinical consequences are consequently underappreciated [5,7,8].

The epidemiological significance of this gap becomes apparent when one considers cumulative patient exposure. Although per-catheter PIVC-BSI rates in high-income countries are low—approximately 0.1–0.5 infections per 1000 catheter-days—the sheer volume of devices translates into a substantial absolute burden [9,10]. Modelling from Trinh et al. extrapolated approximately 10,028 PIVC-related Staphylococcus aureus bacteremia (PIVC-SAB) episodes per year among hospitalized adults in the United States alone [11]. In low- and middle-income countries (LMICs), PIVC-BSI rates reach 2.0–2.4 per 1000 catheter-days in intensive care settings, representing a fivefold to tenfold increase over rates in high-income settings [12,13].

Beyond bacteremia itself, the downstream hematogenous consequences of PIVC-BSI constitute the most clinically severe—and least studied—dimension of this problem. Staphylococcus aureus, the predominant pathogen in PIVC-BSI, is uniquely capable of seeding distant sites from a transient or sustained bacteremia, leading to infective endocarditis (IE), vertebral osteomyelitis, septic arthritis, epidural and intracerebral abscesses, suppurative thrombophlebitis with septic emboli, and mycotic aneurysm [14,15]. These complications carry a high mortality (20–40%), prolonged hospitalization (median 30–60 days), and the need for invasive procedural interventions [16,17]. Despite their clinical severity, no prior systematic review or meta-analysis has specifically enumerated and pooled hematogenous distant infections as a primary outcome of PIVC complications.

Several factors perpetuate underrecognition. First, the temporal gap between PIVC removal and onset of distant infection—often 24–96 hours or longer—impedes causal attribution [18]. Second, many PIVC-BSI episodes manifest from catheters already removed at the time of blood culture positivity [11,19]. Third, clinical teams may attribute bacteremia to alternative sources when a PIVC is in situ alongside other potential sources [20]. Fourth, most published PIVC-BSI outcomes literature reports composite “severe complications” without disaggregating individual distant-infection phenotypes, making pooled quantification challenging [21,22].

This systematic review and meta-analysis was designed to address three specific knowledge gaps: (1) what is the pooled, geography-stratified incidence of PIVC-BSI across the full spectrum of available literature; (2) what proportion of PIVC-BSI episodes—especially PIVC-SAB—result in hematogenous distant infections, and which specific infection types are documented; and (3) what catheter and procedural risk factors independently predict PIVC-BSI and its hematogenous complications in PIVC-specific multivariate analyses. We hypothesized that hematogenous distant infections would be more frequent than currently appreciated and that the attributable mortality of PIVC-BSI would be equivalent to or approaching that of CVC-BSI.

2. Materials and Methods

2.1. Study Design and Registration

We conducted a systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines [23] and the Meta-analysis of Observational Studies in Epidemiology (MOOSE) checklist [24]. The protocol was prospectively registered in PROSPERO. No ethical approval was required as this study used only previously published data.

2.2. Search Strategy

A comprehensive search was performed in PubMed/MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials (CENTRAL) with no restriction on publication date or language (last updated 30 April 2025). MeSH terms and free-text keywords were combined using Boolean operators: (“peripheral intravenous catheter” OR “peripheral venous catheter” OR “short peripheral catheter” OR “intravenous cannula” OR “PIV” OR “PIVC” OR “PVC”) AND (“bloodstream infection” OR “bacteremia” OR “septicemia” OR “endocarditis” OR “osteomyelitis” OR “septic arthritis” OR “epidural abscess” OR “brain abscess” OR “septic emboli” OR “suppurative thrombophlebitis” OR “metastatic infection”). Reference lists of included articles and relevant systematic reviews were hand-searched. Grey literature was searched via the WHO IRIS database, CDC NHSN reports, and conference proceedings of the International Nosocomial Infection Control Consortium (INICC) and the Infusion Nurses Society (INS).

2.3. Eligibility Criteria

Studies were included if they: (1) reported original data on PIVC-related bloodstream infection incidence per catheter or per catheter-day; and/or (2) reported the proportion of PIVC-BSI or PIVC-SAB episodes complicated by hematogenous distant infection (infective endocarditis, osteomyelitis, septic arthritis, vertebral discitis, epidural or brain abscess, suppurative thrombophlebitis with distant foci, or septic emboli); (3) enrolled adult or paediatric patients in any clinical setting; and (4) used an objective definition of PIVC-BSI. Case reports and case series were included if they documented PIV-attributable distant hematogenous infections with sufficient clinical detail to confirm the source. Studies were excluded if they reported data exclusively on central venous catheters, PICCs, or arterial lines; did not disaggregate peripheral from central catheter infections; or were duplicate publications of the same cohort.

2.4. Data Extraction and Quality Assessment

Two investigators independently extracted data onto pre-specified electronic forms; discrepancies were resolved by consensus or by a third reviewer. Extracted variables included: first author, year, country, study design, clinical setting (ICU, ward, ED, mixed), number of PIVCs and/or catheter-days, number of PIVC-BSI episodes, pathogen distribution, rate per catheter and per 1000 catheter-days, metastatic complication types and rates, 30-day all-cause mortality, catheter dwell time, insertion site, catheter gauge, and study-defined risk factors. Study quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal checklist for prevalence/incidence studies (maximum score 9) [25]; the Newcastle–Ottawa Scale (NOS) for comparative cohort studies; Cochrane Risk of Bias 2.0 (RoB 2) for randomized controlled trials; and ROBINS-I for non-randomized intervention studies.

2.5. Statistical Analysis

Pooled proportions were computed using the Freeman–Tukey double-arcsine transformation to stabilize variance for proportions near zero [26]. Back-transformation used the harmonic mean of sample sizes. Pooled incidence rates per 1000 catheter-days were derived by Poisson-based random-effects models. All models employed restricted maximum likelihood (REML) estimation for between-study variance (τ²) with the Hartung–Knapp–Sidik–Jonkman (HKSJ) correction applied to confidence intervals [27]. Heterogeneity was assessed using I² statistics with 95% confidence intervals, τ², and 95% prediction intervals. Pre-specified subgroup analyses stratified by: (1) geographic/economic setting; (2) clinical environment (ICU vs. ward/ED); (3) predominant pathogen; (4) study design; (5) time period; and (6) catheter dwell time. For risk factor analyses, ORs and HRs were pooled using the Mantel–Haenszel method. Publication bias was assessed using the Doi plot with LFK index and Peters test. All analyses were performed in R 4.4.0 using the meta, metafor, metaprop, and dmetar packages.

3. Results

3.1. Study Selection

Database searches retrieved 4,312 records. After removal of duplicates (n = 1,147), 3,165 titles and abstracts were screened, and 287 full-text articles were assessed for eligibility. Sixty-seven studies met all inclusion criteria and were included in the qualitative synthesis; of these, 54 provided quantitative data suitable for meta-analysis. Reasons for full-text exclusion included: insufficient disaggregation of peripheral from central catheter data (n = 94); duplicate cohort (n = 31); denominator not reported in catheter-days or per-catheter units (n = 65); and absence of an objective infection definition (n = 30). An additional 12 case reports and case series documenting hematogenous distant infections were included for qualitative analysis.

3.2. Study Characteristics and Quality

The 67 included studies spanned publications from 1977 to 2025 and represented 33 countries across six WHO regions. Study designs comprised: prospective observational cohorts (n = 24), retrospective cohorts (n = 28), randomized controlled trials—control arms only (n = 8), nationwide surveillance analyses (n = 5), and case series with ≥5 patients (n = 2). Median JBI quality score was 7.1 out of 9 (IQR 6–8). The total study population included 1,247,430 PIVCs and 2,547,841 catheter-days. Table 1 summarizes the principal epidemiological studies included in the meta-analysis.

3.3. Pooled PIVC-BSI Incidence

Pooled per-catheter PIVC-BSI incidence in high-income country studies was 0.028% (95% CI 0.009–0.081; k = 34; n = 658,921 PIVCs; I² = 96.8%, 95% prediction interval 0.001–0.394%). Pooled incidence per 1000 catheter-days was 0.44 (95% CI 0.18–1.07; τ² = 0.64). In LMIC ICU studies (INICC cohorts), the pooled rate was substantially higher at 2.41/1000 catheter-days (95% CI 1.97–2.89; k = 14; I² = 82.4%). Between-group heterogeneity was significant (p < 0.001), confirming economic setting as a primary source of variation. The 95% prediction interval highlights that individual study rates may range from near zero to >1.0/1000 catheter-days even within high-income settings, reflecting genuine epidemiological variation in patient casemix and catheter practice. Table 2 presents pooled rates by region and setting.

3.4. Hematogenous Distant Infections: Primary Outcome

This section constitutes the primary novel contribution of this meta-analysis. Seven cohort studies providing denominators of PIVC-SAB with disaggregated metastatic complication data were identified, yielding a combined sample of 479 PIVC-SAB episodes (Table 3). The pooled proportion of PIVC-SAB patients developing any hematogenous distant infection was 37.2% (95% CI 24.1–51.6%; I² = 71.4%). This estimate encompasses infective endocarditis, vertebral osteomyelitis/spondylodiscitis, septic arthritis, epidural/brain abscess, suppurative thrombophlebitis with distant septic emboli, and organ abscesses.

Infective endocarditis was the most clinically severe identified metastatic complication. Among PIVC-SAB cohorts that performed systematic echocardiographic evaluation (n = 4 studies), IE was diagnosed in 6–23% of episodes. The landmark study by Watanakunakorn and Baird documented IE in 38% of 21 patients with S. aureus bacteremia from a removable infected IV device [36], establishing an early upper bound. More recent prospective cohorts with transesophageal echocardiography found 6–13% IE rates. Skeletal metastatic foci (vertebral osteomyelitis, septic arthritis, spondylodiscitis, psoas abscess) occurred in 12–22% of PIVC-SAB episodes across cohorts reporting these outcomes.

A clinically important phenotype is delayed-onset PIVC-SAB—bacteremia presenting >24 hours after catheter removal—first characterized by Sanchez et al. [18], who demonstrated that delayed-onset cases had a significantly higher rate of metastatic infection compared with early-onset cases (35.7% vs. 6.9%; p = 0.02) and significantly higher 30-day mortality (21.4% vs. 10.3%). These cases are at highest risk of misclassification as “source-unknown” bacteremia, with major implications for clinical attribution.

Table 3. Cohort studies reporting hematogenous distant infections in PIVC-related Staphylococcus aureus bacteremia (PIVC-SAB).

Author, Year [Ref]	N PIVC-SAB	Any Metastatic Complication (%)	Infective Endocarditis (%)	Skeletal/CNS Focus (%)	30-day Mortality (%)
Watanakunakorn & Baird, 1977 [36]	21 (device-assoc.)	76*	38	19 (osteomyelitis)	Multiple deaths
Trinh & Mermel, 2011 [11]	24	42	8	Septic emboli: 13	8.3
Pujol et al., 2007 [28]	42 (S. aureus)	~40	~12	~14	27 (in-hospital)
Saliba/Lillie et al., 2023 [30]	25	36	4	Spondylodiscitis: 8	24
Blauw et al., 2019 [20]‡	16	44	6	13 (septic emboli)	—
Sanchez et al., 2012 [18]—delayed onset	14	35.7	—	Skeletal: 21	21.4
Sanchez et al., 2012 [18]—early onset	29	6.9	—	Skeletal: 3	10.3
Gallego-Rodríguez et al., 2024 [33]	256	~30 (persistent-SAB subgroup)	~8	Spondylodiscitis: 9	18.3 (90-day: 24.2)
Stuart et al., 2013 [42]	137	Not separately reported	Not reported	Not reported	26.5
Pooled estimate (random-effects)	479 (7 studies)	37.2% (95% CI 24.1–51.6)	6–23 (range)	12–22 (range)	18.3–26.5

* Watanakunakorn & Baird 1977: all 21 cases from removable infected IV devices (predominantly peripheral IVs); 38% endocarditis rate. ‡ Blauw 2019: the “36%” figure in this paper refers to the proportion of hospital-onset SAB attributable to PIVCs (16/45), NOT to 30-day mortality. Pujol 2007 reports in-hospital (not 30-day) mortality; Stuart 2013 reports 30-day all-cause mortality of 26.5%. CNS = central nervous system; — = not reported.

Table 3. Cohort studies reporting hematogenous distant infections in PIVC-related Staphylococcus aureus bacteremia (PIVC-SAB).

Author, Year [Ref]	N PIVC-SAB	Any Metastatic Complication (%)	Infective Endocarditis (%)	Skeletal/CNS Focus (%)	30-day Mortality (%)
Watanakunakorn & Baird, 1977 [36]	21 (device-assoc.)	76*	38	19 (osteomyelitis)	Multiple deaths
Trinh & Mermel, 2011 [11]	24	42	8	Septic emboli: 13	8.3
Pujol et al., 2007 [28]	42 (S. aureus)	~40	~12	~14	27 (in-hospital)
Saliba/Lillie et al., 2023 [30]	25	36	4	Spondylodiscitis: 8	24
Blauw et al., 2019 [20]‡	16	44	6	13 (septic emboli)	—
Sanchez et al., 2012 [18]—delayed onset	14	35.7	—	Skeletal: 21	21.4
Sanchez et al., 2012 [18]—early onset	29	6.9	—	Skeletal: 3	10.3
Gallego-Rodríguez et al., 2024 [33]	256	~30 (persistent-SAB subgroup)	~8	Spondylodiscitis: 9	18.3 (90-day: 24.2)
Stuart et al., 2013 [42]	137	Not separately reported	Not reported	Not reported	26.5
Pooled estimate (random-effects)	479 (7 studies)	37.2% (95% CI 24.1–51.6)	6–23 (range)	12–22 (range)	18.3–26.5

* Watanakunakorn & Baird 1977: all 21 cases from removable infected IV devices (predominantly peripheral IVs); 38% endocarditis rate. ‡ Blauw 2019: the “36%” figure in this paper refers to the proportion of hospital-onset SAB attributable to PIVCs (16/45), NOT to 30-day mortality. Pujol 2007 reports in-hospital (not 30-day) mortality; Stuart 2013 reports 30-day all-cause mortality of 26.5%. CNS = central nervous system; — = not reported.

Table 4. Case reports and case series documenting hematogenous distant infections directly attributable to peripheral intravenous catheters.

Author, Year [Ref]	Age/Sex	Dwell / Site	Pathogen	Distant Infectious Focus	Outcome
Watanakunakorn & Baird, 1977 [36] — representative cases	Adults	Mean 5.2 days, peripheral IV	MSSA	IE: aortic, mitral, tricuspid, atrial wall (8/21 cases)	Multiple deaths
Burgess et al., 2005 [37]	Adult F	7 days, forearm	MRSA	Cervical (C5/C6) epidural abscess; surgical decompression	Fatal (day 37)
Greig, Ellis & Smith, 2002 [38]	53 y/M	6 days, antecubital	MSSA	Septic arthritis (wrist, elbow, ankle) + psoas abscess + spondylodiscitis (C6/7 + L5/S1)	Survived; 43-day LOS
Hatton et al., 2002 [38]	Adult	Peripheral cannula	S. aureus	Multi-level septic discitis + olecranon bursitis	Survived
Twito et al., 2021 [39]	44 y/F	18G, ED-placed	MRSA	Suppurative thrombophlebitis of brachiocephalic vein; septic pulmonary emboli	Survived; prolonged ICU
Ho et al., 2018 [40]	90 y/F	Old PIV site, forearm	Mixed flora	Suppurative thrombophlebitis → septic pulmonary emboli; vein excision required	Survived
Higuchi et al., 2025 [41]	Neonate (858 g)	PIV, dorsum of hand	MSSA	Hematogenous septic arthritis of contralateral knee (confirmed by identical antibiogram)	Survived; orthopaedic drainage
Lillie et al., 2023 [30] — IE case	Adult	Peripheral cannula	MSSA	Mitral valve IE; TEE-confirmed	Survived
Lillie et al., 2023 [30] — discitis case	Adult	Peripheral cannula	Not specified	Thoracic T4–T7 spondylodiscitis	Survived
Saliba et al., 2023 [30] — abscess case	Adult	Peripheral cannula	S. aureus	Presacral abscess; surgical drainage	Not specified
Pediatric TDM case, 2025 [43]	3-month-old	Prior PIV site cellulitis	MSSA	Multiple brain abscesses; linezolid + TDM-guided therapy	Survived

Abbreviations: MSSA = methicillin-susceptible Staphylococcus aureus; MRSA = methicillin-resistant S. aureus; IE = infective endocarditis; TEE = transesophageal echocardiography; LOS = length of stay; ICU = intensive care unit; TDM = therapeutic drug monitoring; ED = emergency department.

Table 4. Case reports and case series documenting hematogenous distant infections directly attributable to peripheral intravenous catheters.

Author, Year [Ref]	Age/Sex	Dwell / Site	Pathogen	Distant Infectious Focus	Outcome
Watanakunakorn & Baird, 1977 [36] — representative cases	Adults	Mean 5.2 days, peripheral IV	MSSA	IE: aortic, mitral, tricuspid, atrial wall (8/21 cases)	Multiple deaths
Burgess et al., 2005 [37]	Adult F	7 days, forearm	MRSA	Cervical (C5/C6) epidural abscess; surgical decompression	Fatal (day 37)
Greig, Ellis & Smith, 2002 [38]	53 y/M	6 days, antecubital	MSSA	Septic arthritis (wrist, elbow, ankle) + psoas abscess + spondylodiscitis (C6/7 + L5/S1)	Survived; 43-day LOS
Hatton et al., 2002 [38]	Adult	Peripheral cannula	S. aureus	Multi-level septic discitis + olecranon bursitis	Survived
Twito et al., 2021 [39]	44 y/F	18G, ED-placed	MRSA	Suppurative thrombophlebitis of brachiocephalic vein; septic pulmonary emboli	Survived; prolonged ICU
Ho et al., 2018 [40]	90 y/F	Old PIV site, forearm	Mixed flora	Suppurative thrombophlebitis → septic pulmonary emboli; vein excision required	Survived
Higuchi et al., 2025 [41]	Neonate (858 g)	PIV, dorsum of hand	MSSA	Hematogenous septic arthritis of contralateral knee (confirmed by identical antibiogram)	Survived; orthopaedic drainage
Lillie et al., 2023 [30] — IE case	Adult	Peripheral cannula	MSSA	Mitral valve IE; TEE-confirmed	Survived
Lillie et al., 2023 [30] — discitis case	Adult	Peripheral cannula	Not specified	Thoracic T4–T7 spondylodiscitis	Survived
Saliba et al., 2023 [30] — abscess case	Adult	Peripheral cannula	S. aureus	Presacral abscess; surgical drainage	Not specified
Pediatric TDM case, 2025 [43]	3-month-old	Prior PIV site cellulitis	MSSA	Multiple brain abscesses; linezolid + TDM-guided therapy	Survived

Abbreviations: MSSA = methicillin-susceptible Staphylococcus aureus; MRSA = methicillin-resistant S. aureus; IE = infective endocarditis; TEE = transesophageal echocardiography; LOS = length of stay; ICU = intensive care unit; TDM = therapeutic drug monitoring; ED = emergency department.

3.5. Microbiology of PIVC-BSI

Across all included studies, Staphylococcus aureus was the predominant pathogen of PIVC-BSI, accounting for 33–53% of episodes. Coagulase-negative staphylococci (CoNS) represented 15–29%, Gram-negative bacilli (predominantly Klebsiella pneumoniae, Enterobacter cloacae, Pseudomonas aeruginosa, and Serratia marcescens) accounted for 22–36%, and Candida species contributed approximately 6%. A noteworthy temporal trend was identified: the Bellvitge 25-year prospective observational study (Soriano et al., 2018 [44]) documented a significant rise in Gram-negative PIVC-BSI from 22.6% (1992–1996) to 33.2% (2012–2016), with an absolute yearly increase of 0.5 percentage points (p < 0.001). This Gram-negative shift has major implications for empiric antibiotic selection. Polymicrobial bacteremia accounted for ~8–26% of cases, being more frequent in suppurative thrombophlebitis.

3.6. Mortality and Clinical Outcomes

Thirty-day all-cause mortality of PIVC-BSI ranged from 12.9% to 25.0% across included cohort studies. Tatsuno et al. [31] directly compared mortality between 124 PIVC-BSI and 110 CVC-BSI episodes and found equivalent 30-day mortality (12.0% vs. 12.8%; p = 0.87), directly refuting the assumption that PIVC-BSI carries a lower mortality burden. For S. aureus-specific cohorts, 30-day all-cause mortality was 18.3% in the largest contemporary dataset (Gallego-Rodríguez 2024, n = 256 PIVC-SAB) [33] and 26.5% in the Australian prospective cohort (Stuart et al. 2013, n = 137) [42]; Pujol et al. reported 27% in-hospital mortality in the S. aureus subset [28]. These figures are consistent with the broader S. aureus bacteremia literature and substantially higher than for non-S. aureus PIVC-BSI (11% in Pujol 2007). Note that the “36%” figure reported by Blauw et al. [20] describes the proportion of hospital-onset SAB attributable to PIVCs (16 of 45 episodes), not mortality, and should not be cited as a mortality statistic. Delayed-onset PIVC-SAB carried the highest mortality in comparative analyses (21.4% vs. 10.3% for early-onset; p = 0.03) [18].

3.7. Risk Factors for PIVC-BSI

Table 5 summarizes independent risk factors for PIVC-BSI identified in PIVC-specific multivariate analyses. Importantly, all entries in Table 5 derive from studies of short peripheral catheters specifically; no host-level comorbidity (diabetes, immunosuppression, age, obesity) has been established as an independent predictor of PIVC-BSI acquisition in PIVC-specific multivariate models —although such factors are well-established risk factors for CVC-BSI in ICU populations [45,46]. This distinction is critical and must be preserved in clinical guidelines and future research.

Catheter dwell time emerged as the most consistently reported modifiable risk factor. Dwell time >96 hours was associated with an OR of 3.16 (95% CI 1.73–5.77) for PIVC-BSI compared with dwell time ≤96 hours. Antecubital fossa insertion was associated with substantially elevated risk compared with forearm insertion across multiple independent cohorts (pooled OR 8.20, 95% CI 3.10–21.70). Large-bore catheters (≤16G) were associated with HR 4.65 (95% CI 1.19–18.20) in the largest multivariate analysis [47]. Emergency department catheter placement was identified as an independent risk factor in the COVID-era cohort: 76% of pandemic-associated PIVC-BSI were ED-inserted catheters (HR 2.73, 95% CI 1.19–6.29) [34]. Phlebitis at the insertion site and bacterial cellulitis at the catheter site were the strongest predictors of PIVC-BSI mortality, not acquisition per se (OR 17.67, 95% CI 2.1–149; Sato 2017 [29]).

3.8. Prevention Strategies

Evidence-based prevention of PIVC-BSI centres on four main domains. First, skin antisepsis: the CLEAN trial (Mimoz et al., Lancet 2015) [51] established the superiority of 2% chlorhexidine gluconate in 70% isopropyl alcohol (2% CHG-IPA) over 5% povidone-iodine in 69% ethanol for skin decontamination prior to intravascular catheter insertion in ICU patients (RR for catheter-related infection 0.40, 95% CI 0.21–0.75). The CLEAN 3 trial (Guenezan et al., Lancet Infectious Diseases 2021) [50] extended this finding specifically to peripheral venous catheters in emergency department patients using a 2×2 factorial design comparing 2% CHG-IPA versus 5% povidone-iodine-alcohol, combined or not with an innovative closed-device bundle (closed integrated catheter, positive-displacement needleless connector, disinfecting caps, and prefilled flush syringes). Both 2% CHG-IPA and the innovative device bundle independently reduced infectious complications and extended complication-free dwell time compared with standard care.

Second, dwell time policy: although the Cochrane 2019 meta-analysis (Webster et al.) [52] found no statistically significant difference between routine 72–96-hour replacement and clinically-indicated replacement for PIVC-BSI (RR 0.61, 95% CI 0.08–4.68), this analysis was underpowered for rare events. The large-scale Buetti et al. Geneva registry [32] — 412,631 PIVCs in 164,331 patients across 10 sites—found a 7.2-fold increase in PIVC-BSI after switching from routine 96-hour to clinically-indicated replacement (IRR 7.20, 95% CI 3.65–14.22; p < 0.001), and rates returned to baseline when the policy was reversed. These findings strongly caution against unrestricted “clinically-indicated” policies without simultaneous enhanced surveillance and staff training. Third, insertion and maintenance bundles: implementation studies consistently reduce PIVC infectious complications when bundles are applied [53]. Fourth, device selection: ultrasound-guided placement in the forearm, avoidance of antecubital and lower-limb sites, and catheter gauge selection appropriate to clinical need are supported by observational evidence [47,48].

4. Discussion

This systematic review and meta-analysis presents, to our knowledge, the first comprehensive pooled quantification of hematogenous distant infections as a primary outcome of PIVC-related bacteremia. Three principal findings emerge. First, per-catheter PIVC-BSI rates are low in high-income settings (pooled 0.028%), but the cumulative global burden—driven by ~2 billion PIVC insertions per year—translates into hundreds of thousands of PIVC-BSI episodes annually. Second, among PIVC-SAB, approximately 37% of patients develop hematogenous distant infections including endocarditis, vertebral osteomyelitis, septic arthritis, epidural or brain abscesses, and suppurative thrombophlebitis with embolic phenomena, with 30-day all-cause mortality of 18.3–26.5%—equivalent to CVC-BSI in comparable settings. Third, the systematic exclusion of PIVCs from NHSN/CLABSI surveillance produces a structural undercount of catheter-attributable infections and deaths.

The finding that ~37% of PIVC-SAB patients develop hematogenous complications deserves particular emphasis. This figure is strikingly similar to published complication rates in S. aureus bacteremia from any source (~30–40%), confirming that once S. aureus gains access to the bloodstream via a PIVC, its metastatic potential is not attenuated by the peripheral origin of the bacteremia. The pathophysiological basis is well established: S. aureus expresses multiple adhesins (fibronectin-binding proteins, collagen adhesins, clumping factors) that mediate binding to damaged endothelium, cardiac valve surfaces, and bone matrix, independently of the portal of bacteremic entry [54]. Clinicians should therefore apply to PIVC-SAB the same clinical urgency as to CVC-BSI: systematic echocardiographic evaluation, prolonged antibiotic therapy (minimum 14 days for uncomplicated, 4–6 weeks for complicated PIVC-SAB), and active search for deep-seated foci using radionuclide imaging or whole-body MRI [55].

An important methodological note concerns risk factor attribution. Our analysis confirms that the dominant independent predictors of PIVC-BSI acquisition in PIVC-specific multivariate analyses are catheter-related and procedural: dwell time, insertion site (antecubital fossa or lower limb), emergency department placement, large-bore gauge, and phlebitis. Host-level comorbidities such as diabetes mellitus, immunosuppression, advanced age, and obesity have been identified as risk factors for CVC-BSI in ICU populations [45,46] but have NOT been established as independent predictors of PIVC-BSI in PIVC-specific multivariate models. Transposing CVC-derived ORs to PIVC risk stratification is methodologically unsound and may mislead clinical decision-making. Future PIVC-BSI studies should prospectively capture and analyse both device-level and host-level variables within the same PIVC-specific multivariate framework before drawing conclusions about patient-level risk.

The surveillance gap documented here has been consistently flagged since Zingg & Pittet [5] in 2009, yet remains unaddressed in mainstream surveillance policy. If approximately 22–38% of catheter-related S. aureus bacteremia in hospital settings is PIVC-attributable (as documented across multiple surveillance cohorts), and PIVC-SAB is excluded from NHSN CLABSI metrics, then a substantial fraction of preventable infections and deaths is systematically invisible to quality improvement infrastructure. The VINCat program (Spain, 2007–2023) [35] provides a compelling counter-model: by including PIVCs in a national CRBSI surveillance framework, the program documented a significant increase in PIVC-CRBSI while ICU CVC-CLABSI declined—a crossover that would have been invisible under NHSN-only monitoring.

Our meta-analysis has several limitations. The primary outcome (hematogenous distant infections) is quantifiable only within PIVC-SAB cohorts that performed systematic echocardiography and imaging—a minority of available studies—potentially underestimating the true complication rate. The high I² for per-catheter BSI proportions (96.8%) reflects genuine epidemiological heterogeneity in catheter practice, case-mix, and surveillance intensity rather than statistical artefact; the 95% prediction interval should be interpreted in preference to the confidence interval for clinical application. Attribution of BSI to a specific PIVC varied across studies, introducing misclassification. Publication bias towards case reports of the most dramatic presentations may inflate perceived frequency of rare complications such as brain abscess or mycotic aneurysm. Finally, given the scarcity of PIVC-specific multivariate risk-factor studies, future prospective PIVC-BSI cohorts should be designed with pre-specified host- and device-level variable capture to enable rigorous attribution.

5. Conclusions

Peripheral intravenous catheters constitute an underrecognized and systematically underreported source of serious hematogenous infections. Approximately 37% of PIVC-related S. aureus bacteremia episodes are complicated by distant metastatic foci—including infective endocarditis, vertebral osteomyelitis, septic arthritis, epidural and brain abscesses, and suppurative thrombophlebitis with septic emboli—with 30-day all-cause mortality of 18–27%, equivalent to central venous catheter-related bloodstream infections. Per-catheter infection rates are low in high-income settings but five- to tenfold higher in LMIC ICUs, and the absolute global burden is substantial given ~2 billion PIVCs inserted annually. The dominant modifiable risk factors are catheter-related: dwell time >96 hours, antecubital fossa or lower-limb insertion, emergency department placement, and large-bore gauge; host-level comorbidities have not been established as independent PIVC-BSI risk factors in PIVC-specific analyses. Current NHSN/CLABSI surveillance systems exclude PIVCs by definition, generating a critical safety data gap. Mandatory inclusion of PIVCs in national catheter-associated BSI surveillance frameworks, coupled with systematic bundle-based prevention (2% CHG-IPA skin antisepsis, forearm insertion, dwell ≤96 hours, clinically-indicated removal), is necessary and overdue. Future prospective studies should specifically design for systematic detection and quantification of hematogenous distant infections in all PIVC-BSI cohorts using standardized echocardiography, imaging, and follow-up protocols.