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Background Despite their spread in daily practice, few data is available on clinical factors associated with peripher‑ ally inserted central catheter (PICC)‑related bloodstream infections (PR‑BSI). We aimed to assess the PR‑BSI incidence, microbiology, and factors associated with PR‑BSI with a focus on clinical symptoms. Methods We conducted a retrospective cohort study in a French university hospital. We screened all PICC insertions performed from April 1st, 2018, to April 1st, 2019, and included PICC insertions in adult patients. We assessed the PR‑ BSI incidence, the factors associated with PR‑BSI using a Cox model, and negative and positive predictive values (NPVs and PPVs) of each clinical sign for PR‑BSI. Results Of the 901 PICCs inserted in 783 patients (38,320 catheters days), 214 PICCs (24%) presented with a compli‑ cation. The most prevalent complication was PR‑BSI (1.9 per 1000 catheter days; 8.1% of inserted PICCs ). Enterobac‑ terales (N = 27, 37%) and coagulase negative Staphylococci (N = 24, 33%), were the main microorganisms responsible for PR‑BSI. Factors independently associated with occurrence of PR‑BSI were fever (hazard ratio 13.21, 95% confidence interval 6.00–29.11, p < 0.001) and chills (HR 3.66, 95%CI 1.92–6.99, p < 0.001). All clinical signs and a duration of PICC maintenance ≥ 28 days, had a low PPVs (≤ 67.1%) but high NPVs (≥ 92.5%) for PR‑BSI. Conclusions Monitoring of clinical signs, especially fever and chills, with caution and limitation of device mainte‑ nance duration, could improve PICC management. Keywords PICC, CR‑BSI, Fever, Chills, PICC maintenance duration *Correspondence: Romaric Larcher romaric.larcher@chu‑nimes.fr Department of Microbiology and Infection Control, CHU Nimes, Nimes, France Bacterial Virulence and Chronic Infections, INSERM U1047, University of Montpellier, Montpellier, France Department of Pharmacy, CHU Nimes, Nimes, France Department of Infectious and Tropical Diseases, CHU de Nimes, 1 Place Robert Debré, 30000 Nimes, France Department of Medical Imaging, CHU Nimes, Nimes, France PhyMedExp, INSERM, CNRS, University of Montpellier, Montpellier, France © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Barrigah‑Benissan et al. Antimicrobial Resistance & Infection Control (2023) 12:5 Page 2 of 11 Each PICC insertion request is forwarded to, registered, Background and validated or not by the Pharmacy Department. PICC Since their introduction in late 1970s , peripherally insertion is performed in aseptic conditions according inserted central catheters (PICC, also known as PICC- to the French Society of Infection Control (SF2H) guide- line) widely spread in daily practice. They are indicated lines . After insertion, PICC position is verified with for intermediate-term venous access (7 days to 6 months) a chest X-ray and adjusted if required. Normal saline is for some concrete indications as irritant or vesicant infu- used for preventing lumen occlusion and maintaining sions (total parenteral nutrition or chemotherapy), diffi - PICC patency, as recommended by national and interna- cult venous access and prolonged antimicrobial therapies tional guidelines [2, 20]. . PICC insertion occurs through a peripheral upper arm vein, avoiding iatrogenic complications and ensuring a safe and easy removal compared to other central venous catheters (CVCs) which they partially replaced . Patients Despite some advantages, mechanical complications as We screened all consecutive patients with at least one occlusion, accidental withdrawal , deep venous throm- PICC placement between April 1st, 2018, and April 1st, bosis , and catheter-related bloodstream infections 2019, using the pharmacy registry of PICC insertion (CR-BSIs) [6, 7] were reported during PICC use. Rates requests. All adult patients were included in the study. of PICC-related bloodstream infections (PR-BSIs) com- When a patient had more than one PICC placement, pared to other CVCs infections has been a controversial all PICC placements were considered. Patients under and disputed subject. Now PR-BSI rates are recognized 18-year-old and those lost to follow-up between PICC similar to those of conventional CVCs [8, 9]. Nonethe- insertion and PICC removal were excluded. less, in a recent national public health survey in France, one quarter of the 30 million of catheters implanted every year presented with a CR-BSI. Among these infec- Data collection tions, 16.8% were related to a PICC, making PR-BSI the Patient’s demographic, clinical and biological data were most important and preventable PICC-related complica- collected from the hospital electronic medical record. tion [10–12]. Age, sex, weight, height, body mass index (BMI), medi- Whilst abundant literature is available on PICC cal history, reason for PICC placement, insertion date, related complications, PR-BSI risk factors are still poorly removal date, type of PICC, site of insertion, reason assessed . Published data remains scarce [9, 13–18], for PICC removal, ongoing treatment (especially cor- particularly for medical ward inpatients and outpatients, ticostoreids or other immunosuppressive treatments) since most of the data focuses on intensive care unit and vital status at PICC removal were collected. When (ICU) . a bloodstream sample was diagnosed positive by the A study aiming to assess PICC-related complica- microbiology laboratory, more information was collected tion incidence, with a highlight on PR-BSI, to describe on the laboratory software (number of samples collected, the microorganisms involved and to assess risk factors number of positive samples, central and peripheral blood associated with PR-BSI with a focus on clinical signs, is culture results, insertion site culture and catheter culture lacking. results, lag time between central and peripheral positive blood cultures, microorganism identification and antimi - crobial resistance). Patients’ Charlson comorbidity index Methods was calculated . Microorganisms resistance diagnosis Study aim, design and settings were based on the European Committee on Antimicro- This study aims to assess PICC-related complication inci - bial Susceptibility Testing (EUCAST) guidelines . An dence, particularly the PR-BSI incidence and to describe adjudication committee, made up of an infection control the microorganisms involved and risk factors associated specialist (J.O.), an infectious disease physician (A.S) with PR-BSI with a focus on clinical signs in patients and an intensivist (R.L.), analysed the medical records from a tertiary hospital. to ensure the diagnosis met definition criteria of PICC- We conducted a retrospective, single centre, observa- related infections (PRI) . For each case of BSI, alter- tional cohort study in Nimes University Hospital, from native sources of infection were carefully checked by the April 1st, 2018, to April 1st, 2019. In the medical imaging adjudication committee by reviewing the patient chart department of this 2094-beds University Hospital, single and all microbiological culture results. In case of discrep- or double lumen PICC (Bard Access Systems, Salt Lake ancy, diagnosis was discussed between the committee City, UT, USA) ultrasonography guided insertions are members until a consensus was reached. performed on inpatients and outpatients 5 days a week. Bar rigah‑Benissan et al. Antimicrobial Resistance & Infection Control (2023) 12:5 Page 3 of 11 Definitions Results We defined PRI according to the French Intensive Care From April 1st,2018 to April 1st,2019; amongst 1091 Society (SRLF) guidelines , which are in line with PICCs inserted in 952 patients, 901 PICCs inserted in the Centers for Disease Control and Prevention (CDC) 783 patients met inclusion criteria and were included in and the European Centre for Disease Control and Pre- the analysis (Fig. 1). The median follow-up was 21 days vention (ECDC) guidelines [24–26]. (IQR, 9–43). More than a half of PICCs were removed We defined PICC colonization as a quantitative cath - at the end of intravenous therapy (N = 529; 59%), 38% eter culture ≥ 10 CFU/mL (according to Brun-Buisson) (N = 346) because of a complication and 3% (N = 26) without bacteraemia or clinical signs . after port implantation. The median time for PR-BSI We defined non-bacteraemia PRI (NB-PRI), in the occurrence was 30 (IQR, 16–76). absence of bacteraemia, as a combination of : (i) a quan- Characteristics of the study population are presented in titative catheter culture ≥ 10 CFU/mL and (ii) (a) signs Table 1. The median age for patients with a PICC inser - of local infection (purulent discharge from the PICC tion was 70.9 years (IQR, 59.4–79.8). The median BMI insertion site or tunnel infection); and/or (b) systemic was 24.5 kg/m (IQR, 21.2–28.9). More than a half of signs, with complete or partial resolution of systemic patients had a peripheral vascular disease, a quarter had signs of infection within 48 h after PICC removal . a chronic heart failure and 22% a metastatic cancer. The We defined PR-BSI as an association of: (i) the occur - median Charlson comorbidity index was 6 (IQR, 3–9). rence of either bacteraemia or fungaemia during the Antimicrobial therapy (N = 408; 45%); chemotherapy 48-h period surrounding catheter removal (or a sus- (N = 240; 27%) and difficult venous access (N = 154; pected diagnosis of PRI when the PICC is not removed 17%) were the main reasons for PICC insertion. Inserted immediately); (ii) and either a positive culture with the PICCs had mostly one lumen (N = 712; 79%) and were same microorganism on one of the following samples: inserted in the left basilic or brachial veins (N = 470; insertion site culture, or catheter culture ≥ 10 CFU/ 52%, or N = 209; 24%). The median PICC maintenance mL or positive central and peripheral blood cultures duration was 21 days (IQR, 9–43) accounting for 38,320 with the same microorganism, with a central/periph- catheter days, and PICCs were essentially removed at eral positive blood culture lag time > 2 h, with central the end of IV therapy (N = 529; 59%). However, an acci- blood cultures being positive earlier than the peripheral dental withdrawal before the end of therapy occurred in ones . 69 cases (7%), and PICCs were also removed immedi- ately in case of CR-BSI suspicion (N = 124; 14%) or death (N = 117; 13%). Characteristics of PICCs are summarized Statistical analysis in Table 1. PICC insertion was the unit for statistical analyses. Around one quarter of PICCs (N = 214, 24%) presented Data are described as median and interquartile range with a complication (Table 2). The first complication (IQR) or number and percentage as appropriate. We encountered was PR-BSI (N = 73, 8.1%, 1.9 per 1000 cath- assessed factors associated with PR-BSI using a Cox eter days). Accidental withdrawal (N = 61, 6.8%, 1.6 per model. Factors with a p-value ≤ 0.1 in the univari- 1000 catheter days), vein thrombosis (N = 14, 1.6% and ate analysis were included in the multivariable analy- 0.4 per 1000 catheter days), catheter occlusion (N = 12, sis. Results of the Cox model were reported as hazard 1.3%, 0.3 per 1000 catheter days), local signs of inflam - ratio (HR) with 95% confidence interval (95% CI). We mation (N = 4, 0.4%, 0.1 per 1000 catheter days) and NB- plotted receiver operating characteristic (ROC) curves PRI (N = 3, 0.4%, < 0.1 per 1000 catheter days) were less for clinical signs associated with PR-BSI and for PICC frequent. maintenance duration. We calculated the negative and Among the microorganisms involved in PR-BSI, Enter- positive predictive values (NPVs, PPVs) for each clini- obacterales were the main species (N = 27, 37%), followed cal sign, and identified the optimal cut-off value of by Coagulase Negative Staphylococci (CoNS) (N = 24; catheter duration for PR-BSI occurrence by maximiz- 33%), Staphylococcus aureus (N = 7; 10%), Candida spe- ing the Youden index. All tests were two-sided and cies (N = 7; 10%) and non-fermenting Gram-Negative p-values less than 0.05 were considered statistically sig- Bacilli (N = 5; 7%). Polymicrobial CR-BSI with two spe- nificant. We performed all analyses using R software, cies accounted for 19 cases (26%) and 5 cases (7%) were version 4.2.0 (The R Foundation for Statistical Comput- documented with more than 2 species. Moreover, 47 ing, Vienna, Austria). PICCs presented with a colonization (6.8%, 1.2 per 1000 catheter days), predominantly due to CoNS (N = 33, 70%) and Enterobacterales (N = 6, 13%). Barrigah‑Benissan et al. Antimicrobial Resistance & Infection Control (2023) 12:5 Page 4 of 11 Fig. 1 Flow chart of peripherally inserted central catheters (PICC) placement Characteristics of the species involved in infectious duration ≥ 28 days was very low at 11.2% whereas the complications are listed in Table 3. NPV was at 93.9%. Fever and chills were the most common clinical signs in In the univariate analysis the variables associated with 84% and 64% of patients with PR-BSI, respectively. These occurrence of PR-BSI were: an history of immunosup- two clinical signs showed the best prediction capacity for pressive treatments (either corticosteroids or immu- PR-BSI: area under the ROC curve (AUC) 0.8828, 95%CI nosuppressors, or both; HR 1.79, 95%CI 1.38–2.32, 0.8391–0.9265 for fever and 0.808, 95%CI 0.7524–0.8636 p < 0.001), an history of malignancy (solid tumour or for chills (Fig. 2). Importantly, all clinical signs, namely haematological malignancy; HR 1.68, 95%CI 1.2–2.36, pain or rash at PICC insertion site, fever, chills, or dysp- p = 0.003), dementia (HR 8.25, 95%CI 1.12–61, p = 0.04), noea had high specificity but low sensitivity for PR-BSI insertion of a double-lumen PICC (HR 2.24, 95%CI 1.41– detection (Table 4). Accordingly, the NPVs of clinical 3.58, p < 0.001) and occurrence of clinical signs: pain at signs were satisfactory, especially for fever (98.5%) and insertion site (HR 6.65, 95%CI 3.01–14.7, p < 0.001), rash chills (96.9%), whereas the PPV were low. The higher PPV at insertion site (HR 10.2, 95%CI 4.36–23.8, p < 0.001), were 66.7% for the occurrence of a rash at PICC insertion fever (HR 30.9, 95%CI 16.5–57.7, p < 0.001), chills (HR site and 67.1% for the occurrence of chills (Table 4). 25.6, 95%CI 15.2–43, p < 0.001). As illustrated in the Fig. 3, the risk of PR-BSI increased In the multivariable analysis only fever (HR 13.21, with the duration of PICC maintenance. The risk 95%CI 6.00–29.11, p < 0.001) and chills (HR 3.66, 95%CI increased mainly during the first 6 months with a prob - 1.92–6.99, p < 0.001) were independently associated with ability of PR-BSI at 32.2% (95%CI 22.5–40.7) at day-180. the occurrence of PR-BSI (Table 4). The AUC of PICC maintenance duration for PR-BSI development was 0.6349, 95%CI 0.5715–0.6984 and the Discussion optimal cut-off value of catheter day associated with PR- This retrospective cohort study reports the results of BSI development was 28 days. Similar to clinical signs, 901 PICC insertions in 783 patients accounting for the PPV for PR-BSI development of a PICC maintenance 38,320 catheters days. 214 PICCs (24%) presented with Bar rigah‑Benissan et al. Antimicrobial Resistance & Infection Control (2023) 12:5 Page 5 of 11 Table 1 Characteristics of the study population and peripherally inserted central catheters (PICC) Total (N = 901) N (%) or median No PR-BSI (N = 828) N (%) or median PR-BSI (N = 73) (IQR) (IQR) N (%) or median (IQR) Patients, N 783 713 70 Sex ratio M/F 500/401 461/367 37/33 Age (year) 70.9 (IQR, 59.4–79.8) 71.0 (IQR, 59.8–80.5) 69.8 (IQR, 58.8–74.1) Body Mass Index (kg/m ) 24.5 (IQR, 21.2–28.9) 23.8 (IQR, 20.7–28.1) 24.4 (IQR, 21.1–28.7) Charlson comorbidity index 6 [3–9] 6 [3–8] 7 [4–10] Main comorbidities Corticosteroids 141 (18%) 112 (16%) 29 (41%) Immunosuppressors 101 (13%) 78 (11%) 23 (33%) Solid tumour 142 (18%) 129 (18%) 13 (19%) Metastatic solid tumour 178 (23%) 151 (21%) 27 (38%) Haematological malignancy 69 (9%) 51 (7%) 18 (26%) Leukaemia 46 (6%) 36 (5%) 10 (14%) Lymphoma 23 (3%) 15 (2%) 8 (11%) PICC lumen 1 lumen 712 (79%) 669 (81%) 43 (59%) 2 lumens 189 (21%) 159 (19%) 30 (41%) Reason for PICC insertion Antimicrobial therapy 408 (45%) 397 (48%) 11 (15%) Chemotherapy 240 (27%) 201 (24%) 39 (53%) Difficult venous access 154 (17%) 143 (17%) 11 (15%) Total parenteral nutrition 52 (6%) 44 (5%) 8 (11%) Iterative venous access 47 (5%) 43 (5%) 4 (5%) Insertion site Left basilic vein 470 (52%) 436 (53%) 34 (47%) Right basilic vein 135 (15%) 124 (15%) 11 (15%) Left brachial vein 209 (24%) 189 (22%) 21 (29%) Right brachial vein 72 (8%) 67 (8%) 5 (7%) Left cephalic vein 12 (1%) 10 (1%) 2 (3%) Right cephalic 1 (< 1%) 1 (< 1%) 0 (0%) Femoral 1 (< 1%) 1 (< 1%) 0 (0%) PICC maintenance (days) 21 (IQR, 9–43] 20 (IQR, 9–41] 30 (IQR, 16–76) Reason for PICC removal End of IV therapy 529 (59%) 529 (64%) 0 (0%) Accidental withdrawal 61 (7%) 60 (7%) 1 (1%) PR‑BSI suspicion 124 (14%) 62 (7%) 62 (85%) Positive blood culture 5 (1%) 2 (<1%) 3 (4%) Vein thrombosis 18 (2%) 17 (2%) 1 (<1%) PICC occlusion 12 (1%) 11 (1%) 1 (<1%) Local inflammation 9 (1%) 8 (1%) 1 (<1%) Port implantation 26 (3%) 25 (3%) 1 (<1%) Death 117 (13%) 114 (14%) 3 (4%) BSI Bloodstream infection, COPD Chronic obstructive pulmonary disease, IQR Interquartile range, PR-BSI PICC related bloodstream infection, IV Intravenous highlighted the importance of clinical signs fo PR-BSI a complication, mainly a PR-BSI (N = 73, 8.1%) with a monitoring, reporting fever and chills as factors indepen- 1.9 per 1000 catheter days incidence rate. Enterobac- dently associated with PR-BSI occurrence. terales (N = 27, 37%) and CoNS (N = 24, 33%) were the Over the last decade, PICC use increased in hospitals main microorganisms involved in PR-BSI. Moreover, we , particularly in university hospitals . PR-BSIs Barrigah‑Benissan et al. Antimicrobial Resistance & Infection Control (2023) 12:5 Page 6 of 11 Table 2 Type, rate and incidence of peripherally inserted central studies were reported unsuitable for research . None- catheters (PICC) complications theless, we must acknowledge the PR-BSI incidence rate found in this study was above the 1 per 1000 catheter Complications Number Rates (%) Incidence (per of PICC 1000 catheter days threshold target for CR-BSI prevention intervention days) suggested by infection control experts . In this global context, CVCs and particularly PICC were pointed as PR‑BSI 73 8.1 1.9 priorities for infection prevention measures . Multi- Accidental withdrawal 61 6.8 1.6 modal process for better CR-BSI prevention and control PICC colonization 47 5.2 1.2 including practice change based on knowledge, educa- Vein thrombosis 14 1.6 0.4 tion, and behavioural interventions in our hospital are Catheter occlusion 12 1.3 0.3 encouraged . Recent guidelines  suggested, prac- Local inflammation 4 0.4 0.1 tical healthcare workers team education and training, NB‑PRI 3 0.3 < 0.1 promoted by a multidisciplinary team with checklists, PR-BSI PICC related bloodstream infection, NB-PRI Non bacteraemia PICC related continuous improvement programs and bundles imple- infection mentation . Another significant finding of this work was the impor - also increased at the same time [10, 28, 29]. One impor- tance of clinical monitoring of PR-BSI. Indeed, this study tant finding of this study was the 1.9 per 1000 catheter identified a strong correlation between clinical signs such days incidence rate of PR-BSI, which was in line with as fever and chills, and PR-BSI. Most importantly, clini- the median 2.1 per 1000 catheter days incidence rate cal signs showed high specificity and NPV but unsatisfac - reported in meta-analyses of international studies [9, tory sensibility and PPV. The absence of clinicals signs is 30, 31]. Previous studies found various incidence rates therefore significantly indicative of the absence of PR-BSI ranging from 0.6 to 3.3 per 1000 catheter days [4, 16–18, as suggested by others in ICU settings . Amongst 32]. Importantly, differences in PR-BSI incidence may be clinical signs, fever and chills have the best NPVs. Fever related to the time period of the studies and differences in was previously reported as indicative of CR-BSI along catheter-related infection definitions across these stud - with other infection signs [37, 38]. In line with previous ies . Moreover, several definitions used in numerous studies [39–41], we reported that prolonged duration of Table 3 Species involved in infectious complications of peripherally inserted central catheter (PICC) Species PR-BSI (N, %) PICC colonization (N, %) Total (N, %) Gram positive cocci Coagulase Negative Staphylococci 24 (33%) 33 (70%) 57 (48%) Linezolid resistant 2 (3%) 0 (0%) 2 (2%) Staphylococcus aureus 7 (10%) 1 (2%) 8 (7%) MRSA 5 (7%) 0 (0%) 5 (4%) Enterococcus spp 2 (3%) 1 (2%) 3 (2.5%) Streptococcus spp 1 (1%) 0 (0%) 1 (1%) Gram negative bacilli Enterobacterales 27 (37%) 6 (13%) 33 (28%) 3GCR 28 (38%) 0 (0%) 28 (23%) ESBL 10 (14%) 0 (0%) 10 (8%) AMPC 16 (23%) 0 (0%) 16 (13%) CRE 7 (10%) 0 (0%) 7 (6%) Non‑fermenters 5 (7%) 3 (6%) 8 (7%) Pip‑ Taz resistant P. aeruginosa 2 (3%) 0 (0%) 2 (2%) Ceftazidime resistant P. aeruginosa 1 (1%) 0 (0%) 1 (1%) CR P. aeruginosa 1 (1%) 0 (0%) 1 (1%) Candida spp. 7 (10%) 3 (6%) 11 (9%) Total 73 47 120 CR Carbapenem resistant, CRE Carbapenem resistant Enterobacterales, ESBL Extended spectrum beta‑lactamase, MRSA Methicillin resistant Staphylococcus aureus, rd Pip-Taz Piperacillin‑tazobactam, PR-BSI PICC related bloodstream infection, 3GCR 3 generation cephalosporin resistance Bar rigah‑Benissan et al. Antimicrobial Resistance & Infection Control (2023) 12:5 Page 7 of 11 was associated with very low PPV but satisfactory NPV for PR-BSI, as previously reported . These results sug - gest a close clinical signs monitoring could rapidly help diagnose and treat PR-BSI particularly in patient with a prolonged PICC dwelling time. These results also sup - ports the recent recommendation of catheter duration limitation to the shortest requested to limit PR-BSI . Available data also suggests that clinicians should limit the number of catheter lumen [9, 14, 43] and concurrent catheter . Immunocompromised patients, particularly those treated with immunosuppressive treatments and/or with metastatic cancer have been identified at risk for PR-BSI. Immunosuppression, particularly neutropenia, was pre- viously reported as risk factor for PR-BSI [40, 44–47], prompting clinicians to monitor PICC in immunocom- promised patients with caution. Surprisingly, those patients did not seem at higher risk for PR-BSI in our study. During the study, a high nurse-to-patient ratio in Fig. 2 Receiver operating characteristics (ROC) curves for haematology and oncology wards, local guidelines, and peripherally inserted central catheter (PICC)‑associated bloodstream specific courses on PICC use for nurses were available infection on the basis of the number of catheter days (red line) and clinical signs such as pain (blue dashed line), rash at the PICC in our institution. This may have impacted the quality of insertion site (green pointed line), fever (orange dashed line), chills PICC care which has been widely reported to decrease (purple dashed line), dyspnea (black dashed line). Area under the ROC PR-BSI incidence rate . curves (AUCs) are given with the 95% confidence interval (95% CI) Previous studies on PR-BSI microbiology reported CoNS as the predominant microorganisms [11, 13, 39, 48]. Nonetheless, recent evidences [48–51] suggested a change in this trend with the rising of Gram negative catheterization increased the risk for PR-BSI (see sup- bacilli as main microorganisms associated with PR-BSI. plementary materials). However, our work underlined With a majority of PR-BSI related to Enterobacterales the poor ability of PICC maintenance duration to predict (37%), the results of our study tend to support the later. PR-BSI. Indeed, the threshold value of 28 catheter days Table 4 Factors independently associated with peripherally inserted central catheters (PICC) related bloodstream infection (PR‑BSI), and predictive values of clinical signs for PR‑BSI Multivariate analysis Diagnostic ability of clinical signs Variables Hazard ratio 95% CI p-value Sensitivity Specificity PPV NPV Patient conditions Immunosuppr. therapy 1.07 0.80–1.43 0.63 – – – – Malignancy 1.08 0.67–1.75 0.75 – – – – Dementia 1.62 0.18–14.58 0.67 – – – – Clinical signs Local signs Pain 0.55 0.17–1.81 0.33 9.6% 98.7% 38.8% 92.5% Rash 2.82 0.82–9.69 0.10 8.2% 99.6% 66.7% 92.5% Systemic signs Fever 13.21 6.00–29.11 < 0.001 83.6% 93.0% 51.3% 98.5% Chills 3.66 1.92–6.99 < 0.001 64.4% 97.2% 67.1% 96.9% Dyspnoea 1.24 0.53–2.94 0.62 12.0% 99.4% 64.3% 93.0% PICC duration ≥ 28 days – – – 53.4% 62.8% 11.2% 93.9% 1 2 at least one of the following: corticosteroids, azathioprine, mycophenolate mophetil, tacrolimus, ciclosporin. solid tumour or haematological malignancy. PPV Positive predictive Value, NPV Negative Predictive Value, 95% CI 95%confidence interval Barrigah‑Benissan et al. Antimicrobial Resistance & Infection Control (2023) 12:5 Page 8 of 11 an anticoagulant therapy. This may have limited the inci - dence rate of thrombosis in our cohort. This study has several limitations. First, the single cen - tre design of the study could limit extrapolation of the results. Second, the relatively small size of our cohort limited the weight of some factors such as BMI > 40 kg/ m , number of lumen or total parenteral nutrition which are recognized at risk factors for CR-BSI [40, 57]. How- ever, to the best of our knowledge, this study is the first to analyse the association between clinical signs and PR- BSI. Third, the retrospective design of the study limits our analyses to available data in medical records and may induce bias in data collection and results interpretation. Some risk factors such as the microbial colonization at Fig. 3 Incidence of peripherally inserted central catheters (PICC) the catheter hub and at insertion site, or the outpatient/ related bloodstream infection during PICC maintenance (in days) with 95% confidence interval inpatient status, could not be assessed. However, com- bining medical, microbiological, and administrative data, added to the adjudication committee for PR-BSI diag- nosis in accordance with international expert consensus Yet, CoNS are still significantly associated with PR-BSI tends to limit this bias. (33%) and responsible for most of PICC colonisations. The large proportion of immunocompromised patients Conclusions in our cohort (almost a half of patients had a haemato- Complications occurred in 24% of PICC, and PR-BSI was logical malignancy or a cancer, and more than two thirds the most prevalent one with a 1.9 per 1000 catheter days of patients with a PR-BSI), may explain the high preva- incidence rate. PR-BSIs were mainly caused by Entero- lence of Enterobacterales associated PR-BSIs since these bacterales and CoNS. Clinical signs and PICC mainte- patients are most at risk to be infected with their own nance duration ≥ 28 catheter days, had better NPVs than Enterobacterales . Another possible explanation for PPVs for PR-BSI diagnosis. Fever and chills had the best these results was the inclusion of patients in home-hos- NPV and were independently associated with PR-BSI pitalization. This finding has important implications for occurrence. the implementation of infection control bundle in PR-BSI These results suggest that health workers should cau - prevention, especially regarding hand disinfection and tiously monitor PICC insertion site, and especially fever skin antisepsis during PICC care and dressing manage- and chills, and limit the duration of PICC maintenance ment [12, 35]. to the minimum required. They also prompt patients to This study also reported low rates of PICC related self-monitoring. Further studies are mandatory to assess complications other than PR-BSI. We found an acci- whether improving patients and healthcare workers edu- dental withdrawal incidence rate of 1.6 per 1000 cath- cation on PICC management through the development eter days (N = 61, 6.8%), lower than those reported by of an infection prevention bundle and continuous evalua- Valbousquet et al. (2.8 per 1000 catheter days)  and tion could reduce PR-BSI under 1 per 1000 catheter days. Grau et al. 8.0% . However, others found lower rates at 2.4%  and 5% , respectively, but reported rates instead of incidence which limited comparison with our Abbreviations AUC Ar ea under the ROC curve results. Importantly, accidental withdrawal was identi- BMI Body mass index fied as a common complication in PICC use especially CDC Centers for disease control and prevention in patients older than 70 year-old, which is the median CoNS Coagulase negative staphylococci CR Carbapenem resistant age in our study population [16, 53]. We reported a vein CRE Carbapenem resistant enterobacterales thrombosis incidence rate at 0.4 per 1000 catheter days, CR‑BSI Catheter‑related bloodstream infections also lower than those previously reported [19, 53, 54]. CVC Central venous catheters ECDC E uropean centre for disease control and prevention PICCs are described as more thrombogenic than CVCs ESBL Extended spectrum beta‑lactamase [19, 55], particularly in cephalic vein position . Con- EUCAST European committee on antimicrobial susceptibility testing sequently, PICC were mainly inserted in basilic, or bra- HR Hazard ratio IQR Interquartile range chial vein as recommended in our local protocol. In MRSA Methicillin resistant Staphylococcus aureus addition, more than a third (27%) of the patients received NB‑PRI Non‑bacteraemia PRI Bar rigah‑Benissan et al. Antimicrobial Resistance & Infection Control (2023) 12:5 Page 9 of 11 NPV Negative predictive value Centre cohort study. Thromb J. 2019;17:2. https:// doi. org/ 10. 1186/ PICC Peripherally inserted central catheters12959‑ 019‑ 0191‑y. Pip‑Taz Piperacillin‑tazobactam 6. Chopra V, O’Malley M, Horowitz J, Zhang Q, McLaughlin E, Saint S, et al. PPV Positive predictive value Improving peripherally inserted central catheter appropriateness and PR‑BSI PICC‑related bloodstream infection reducing device‑related complications: a quasiexperimental study in 52 ROC Receiver operating characteristic Michigan hospitals. BMJ Qual Saf. 2022;31:23–30. https:// doi. org/ 10. 1136/ SF2H French society of infection controlbmjqs‑ 2021‑ 013015. SRLF French intensive care society 7. Ajenjo MC, Morley JC, Russo AJ, McMullen KM, Robinson C, Williams RC, 3GCR 3rd generation cephalosporin resistance et al. Peripherally inserted central venous catheter‑associated blood‑ 95%CI 95% confidence interval stream infections in hospitalized adult patients. Infect Control Hosp Epidemiol. 2011;32:125–30. https:// doi. org/ 10. 1086/ 657942. Acknowledgements 8. Chopra V, O’Horo JC, Rogers MAM, Maki DG, Safdar N. The risk of blood‑ None. stream infection associated with peripherally inserted central catheters compared with central venous catheters in adults: a systematic review Author contributions and meta‑analysis. Infect Control Hosp Epidemiol. 2013;34:908–18. Conceptualization, A.S. and R.L.; methodology, A.S. and R.L.; software, K.B.‑B. https:// doi. org/ 10. 1086/ 671737. and R.L; validation, J.O., A.S., R.L, and J.‑P.L.; formal analysis, K.B.‑B., J.O., A.S. and 9. Chopra V, Ratz D, Kuhn L, Lopus T, Chenoweth C, Krein S. PICC‑associated R.L.; investigation K.B.‑B.; writing—original draft preparation, K.B.‑B.; writing— bloodstream infections: prevalence, patterns, and predictors. Am J Med. review and editing, J.O., R.L., and A.S.; supervision, R.L.; project administration, 2014;127:319–28. https:// doi. org/ 10. 1016/j. amjmed. 2014. 01. 001. C.S., A.M., J.‑P.B., A.S. and R.L. All authors reviewed the final version of the 10. Van Der Mee‑Marquet N, Marie D, Rémi G, Florent G. Surveillance des manuscript. infections associées aux dispositifs invasifs. Mission nationale SPIADI. Résultats de la surveillance menée en 2019; 2019. https:// www. sante Fundingpubli quefr ance. fr/ malad ies‑ et‑ traum atism es/ infec tions‑ assoc iees‑ aux‑ This research received no external funding.soins‑ et‑ resis tance‑ aux‑ antib iotiq ues/ infec tions‑ assoc iees‑ aux‑ soins/ docum ents/ rappo rt‑ synth ese/ surve illan ce‑ des‑ infec tions‑ assoc iees‑ aux‑ Availability of data and materialsdispo sitifs‑ invas ifs.‑ missi on‑ natio nale‑ spiad i.‑ resul tats‑ de‑ la‑ surve illan The authors consent to share the collected data with others. The raw data sup‑ce‑ menee‑ en‑ 2019. Accessed 14 Oct 2022. porting the conclusions of this article will be made available by the authors, 11. Lee JH, Kim ET, Shim DJ, Kim IJ, Byeon JH, Lee IJ, et al. Prevalence without undue reservation. Data will be available immediately after the main and predictors of peripherally inserted central catheter‑associated publication and indefinitely. bloodstream infections in adults: a multicenter cohort study. PLoS ONE. 2019;14:e0213555. https:// doi. org/ 10. 1371/ journ al. pone. 02135 55. 12. Buetti N, Timsit J‑F. Management and prevention of central venous Declarations catheter‑related infections in the ICU. Semin Respir Crit Care Med. 2019;40:508–23. https:// doi. org/ 10. 1055/s‑ 0039‑ 16937 05. Ethics approval and consent to participate 13. Bessis S, Cassir N, Meddeb L, Remacle AB, Soussan J, Vidal V, et al. Early The Institutional Review Board of Nimes University Hospital approved the mortality attributable to PICC‑lines in 4 public hospitals of Marseille from study protocol (No. 22.03.06) and waived the need for signed patient consent. 2010 to 2016 (Revised V3). Medicine (Baltimore). 2020;99:e18494. https:// doi. org/ 10. 1097/ MD. 00000 00000 018494. Consent for publication 14. Pongruangporn M, Ajenjo MC, Russo AJ, McMullen KM, Robinson C, Not applicable. Williams RC, et al. Patient‑ and device ‑specific risk factors for peripherally inserted central venous catheter‑related bloodstream infections. Infect Competing interests Control Hosp Epidemiol. 2013;34:184–9. https:// doi. org/ 10. 1086/ 669083. The authors declare that they have no competing interests. 15. Milstone AM, Reich NG, Advani S, Yuan G, Bryant K, Coffin SE, et al. Cath‑ eter dwell time and CLABSIs in neonates With PICCs: a multicenter cohort study. Pediatrics. 2013;132:e1609–15. https:// doi. org/ 10. 1542/ peds. Received: 10 November 2022 Accepted: 21 January 2023 2013‑ 1645. 16. Grau D, Clarivet B, Lotthé A, Bommart S, Parer S. Complications with peripherally inserted central catheters (PICCs) used in hospitalized patients and outpatients: a prospective cohort study. Antimicrob Resist Infect Control. 2017;6:18. https:// doi. org/ 10. 1186/ s13756‑ 016‑ 0161‑0. 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Antimicrobial Resistance and Infection Control – Springer Journals
Published: Jan 30, 2023
Keywords: PICC; CR-BSI; Fever; Chills; PICC maintenance duration
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