Peripherally inserted central catheter line-induced fevers: a case report

Abstract

Background

Peripherally inserted central catheter lines are increasingly common as medical innervation advances. Peripherally inserted central catheter lines are generally well tolerated with few complications, the most common being pain, bleeding, line dislodgement or blockage. However, there are more serious complications such as line sepsis.

Case presentation

We present a case of a 32-year-old Indian woman with recurrent fever in the context of sterile peripherally inserted central catheter lines.

Conclusion

Noninfectious fevers can occur in patients with peripherally inserted central catheter lines with the underlying mechanism not being certain.

Introduction

Peripherally inserted central catheter (PICC) lines provide reliable, easy central vascular access for patients in a variety of clinical settings such as prolonged courses of intravenous antibiotics, chemotherapy, blood sampling, or total parenteral nutrition (TPN) administration [1]. PICC line-associated reactions are rare and generally relate to allergy to product materials, extravasation, or blockages of the line. Furthermore, atypical infections and their complications secondary to PICC lines are often cited in case reports. Here, we report a rare case not previously described in literature of persistent fever related to recurrent sterile/culture-negative PICC line in an immune-competent patient with a postoperative infection requiring prolonged antibiotics.

Case presentation

A 32-year-old Indian woman presented to hospital with evidence of a chronic neurosurgical wound infection, with pus being discharged from the scalp wound, following an arteriovenous malformation repair several months previously. She was systemically well with suppressed inflammatory markers.

Aside from the previous arteriovenous malformation requiring a previous craniotomy and polycystic ovarian syndrome, she had no other past medical history and took no regular medications apart from occasional paracetamol or codeine. She was allergic to ibuprofen. She lived with her husband and young son. She did not smoke or drink alcohol, and there was no history of illicit drug use or over the counter supplements. She had no travel history.

Magnetic resonance imaging (MRI) of the head on admission showed postsurgical changes with fluid collection and minimal associated mass effect. She was managed surgically with an exploratory wash-out under the neurosurgical team. Extradural fluid showed white cells but no organisms; bacterial and fungal RNA was negative as was acid-fast bacilli (AFB). Skin swab culture was negative, and bone culture was positive for Cutibacterium acnes (which was thought to be a contaminant).

Antibiotics were started after surgery and sample collection and guided by a microbiologist. The patient was initially treated with meropenem and teicoplanin. A PICC line was inserted in the right arm on day 4; however, she developed pain in the arm and shoulder girdle immediately post-insertion. Subsequently, 2 days later, a chest x-ray showed a satisfactory position. A Doppler 2 days following this showed subcutaneous edema around the right cephalic vein, possibly felt to be secondary to extravasation, and so the PICC was removed and a new line inserted on the left side on day 8. However, within 4 days, she had ongoing discomfort; a repeat chest x-ray (CXR) and ultrasound Doppler of the new left-sided PICC were performed, and the results were satisfactory for both.

She developed her first temperature on day 10 of admission, and antibiotics were switched to ceftriaxone and vancomycin. Temperatures were high (consistently over 38 °C) and associated with tachycardia, although not related temporally to PICC line access or usage.

Computed tomography (CT) of the neck, thorax, abdomen, and pelvis was performed given her temperature spikes and evidence of swollen bilateral cervical lymph nodes on clinical examination. No other significant clinical examination findings were noted, in particular, there was no focal neurology. The CT showed no evidence of collections, but it did show reactive lymph nodes in the neck. Her left-sided PICC line was removed on day 19 and sent for culture to rule it out as a possible source of infection. However, the culture was negative.

On day 21, a new PICC line was reinserted on the left side owing to difficulties with vascular access. In the preceding days she had continued to receive antibiotics via a peripheral cannula and had been apyrexial during this time. She developed another temperature later that afternoon. She completed a week of ceftriaxone before she was switched back to meropenem to continue with vancomycin, and a STAT dose of gentamicin was also given at this time. A week later, repeat ultrasound Doppler showed segmental thrombus around the line in the basilic vein, and the line was removed and antibiotics were stopped (day 27). She was apyrexial immediately after this and remained apyrexial for the rest of her hospital admission. She remained antibiotic-free for 4 days before starting oral antibiotics, with the aim to discharge on oral antibiotics (doxycycline and levofloxacin) to continue treatment in the community. A summary of the timeline is provided below (Fig. 1) with a graph showing her temperatures over this period (Fig. 2). Her inflammatory markers were low on admission. Figure 3 shows a summary of relevant laboratory results that remained relatively suppressed throughout this time. Peripheral blood films were unremarkable, and white cell count differential was also unremarkable.

Fig. 1.

Clinical timeline. Summary of the patient’s clinical course, with key events and management decisions

Fig. 2.

Temperature trend during the admission. Temperature recordings during the admission period. The green circle depicts the 24-hour apyrexial period between removal and reinsertion of the peripherally inserted central catheter line

Fig. 3.

Laboratory results. Summary of white cell count and C-reactive protein during periods of the clinical course

The patient was extensively cultured during this time. Both blood cultures (peripherally and from PICC lines) and urine cultures were negative. Her CT of the neck/pelvis did not show any alternative cause for her fevers, and she had a whole-body CT–positron emission tomography (PET) that showed reactive cervical lymph nodes bilaterally only. These were biopsied and confirmed to be reactive. In addition, AFB was negative. The patient never had any focal neurological symptoms or headache, and her wound remained clean. She had two follow-up MRI scans during this admission that showed improving appearance of the collection with nonreactive adjacent parenchyma. She was also tested for an array of other causes for her fever, all of which were negative. These included: respiratory viral panels, throat swab, human immunodeficiency virus (HIV), Epstein–Barr virus (EBV), cytomegalovirus (CMV), and malaria, including parasites, toxoplasmosis, typhoid, spotted fever, Brucella, Borrelia, and tuberculosis (TB). The brand of PICC line used was consistent and both latex- and Di(2-ethylhexyl) phthalate (DEHP)-free.

As this was a diagnosis of exclusion, the main diagnostic challenge was the time it took to rule out other infectious and noninfectious causes of fevers. This understandably led to a prolonged hospital admission, which was challenging for the patient as she had a young child at home. However, she recovered well and was discharged home with a course of oral antibiotics. She has since returned for completion of a bifrontal cranioplasty.

Discussion

Peripherally inserted central catheters (PICCs) are an essential component of modern medical practice, particularly for the delivery of medium- to long-term intravenous therapies. Their use has become commonplace across inpatient and outpatient settings owing to their relative ease of insertion and perceived safety compared with centrally inserted central venous catheters (CVCs). However, despite their advantages, PICCs are not without complications. One large study reported that 17% of patients developed complications, corresponding to an incidence of 1.59 per 1000 catheter days [2]. While infection rates are often considered similar to those of centrally inserted catheters, PICCs are frequently retained for longer periods, potentially increasing cumulative exposure to complications [2].

The complication rate associated with PICCs varies widely in literature, with estimates ranging between 7.5% and 17.5%, likely reflecting differences in patient populations, catheter types, insertion techniques, and maintenance protocols [3]. Among the most commonly reported complications are pain at the insertion site (39.9%), bleeding (20%), dislodgement (20%), superficial thrombophlebitis (7%), infection (6–10%), and leakage (6%). In specific populations, such as patients with cancer, additional complications, including skin allergy (4.6%) and upper extremity deep vein thrombosis (1.9%) have also been observed. Furthermore, the risk of thrombosis may be higher in hospitalized patients and is influenced by factors such as catheter-to-vein ratio, catheter size, and patient comorbidities.

Although rare, systemic hypersensitivity reactions associated with PICC lines have been documented and may present dramatically. A study of over 8000 PICC insertions in Canadian tertiary centers reported 37 cases of acute anaphylactoid reactions, all of which occurred within minutes of catheter insertion [2]. Notably, these reactions were strongly associated with PICCs containing magnetized stylets and were significantly more frequent in patients with cystic fibrosis (CF), who exhibited a 10–20-fold increased risk. The underlying mechanism remains speculative, though the authors hypothesized a possible IgE-mediated response, possibly potentiated by chronic antibiotic exposure in CF populations. The presence of heavy metals such as nickel or silver in catheter components may also contribute to mast cell activation and hypersensitivity responses. These findings led to the discontinuation of magnetized stylet PICCs in the study centers.

Chlorhexidine, a widely used antiseptic in PICC line insertion and maintenance, has also been implicated in severe hypersensitivity reactions, including urticaria, anaphylaxis, and even death [4]. These reactions can be difficult to distinguish from catheter material sensitivities, and it is important that clinicians consider all potential allergenic exposures in cases of unexplained systemic responses during or after PICC placement.

Historically, Mermel et al. (1995) reported adverse hypersensitivity reactions linked to a specific brand of PICC line, manifesting as acute onset urticaria, abdominal pain, dyspnea, and erythroderma shortly after line insertion [5]. In several cases, symptoms resolved promptly upon catheter removal. These reports were submitted to the Food and Drug Administration and led to changes in procurement practices across several institutions.

Extravasation is a recognized complication of central venous access, particularly with subclavian or internal jugular lines, but is rarely reported with PICCs. It is more commonly described in pediatric literature or in cases of catheter migration. Johnson et al. (2010) reported two cases of elderly patients developing chylothorax following line manipulation under fluoroscopic guidance [6]. Both patients had received total parenteral nutrition, and the authors hypothesized that line erosion or vessel wall compromise may have played a role. While risk factors such as advanced age and hyperosmolar infusates are associated with erosion-related complications, these were not applicable in our case.

Infectious complications may also present atypically. A case report by Douedi, Fadhel, and Patel (2020) described a middle-aged patient with diabetes who developed an axillary abscess caused by Nocardia otitidiscaviarum following PICC insertion [7]. Nocardia species are known for biofilm formation, which can facilitate catheter colonization and seeding of deep-seated infections, particularly in immunocompromised hosts or those with underlying colonization. This case highlights the potential for opportunistic infections in patients with PICC lines and the diagnostic challenge posed by unusual pathogens.

Postoperative fever is common and typically multifactorial. It may arise from a physiological inflammatory response, infection, or noninfectious causes such as hematoma, drug reaction, or venous thromboembolism. Labbus et al. (2018) report that up to 95% of postoperative fevers may remain without an identifiable cause [8]. Drug-induced fever, although a diagnosis of exclusion, must always be considered. It typically occurs several days into antibiotic therapy and resolves promptly on cessation of the offending agent. Beta-lactam antibiotics, particularly piperacillin/tazobactam, are among the most frequently implicated. Although rash and eosinophilia are variably present, raised inflammatory markers, leukopenia, and deranged liver function tests are common findings.

In this case, the patient developed her first fever 7 days after initiation of antibiotics. However, the lack of a clear temporal link with drug administration and the resolution of fever despite continuation of the same antibiotic via a peripheral line, strongly argued against a drug-induced etiology for her fevers. Instead, the resolution of fever following PICC removal suggested a catheter-related cause. Importantly, this occurred in the absence of clear line sepsis, positive cultures, alternative atypical infection, or overt clinical, radiological, or biochemical signs of infection.

It is possible that subclinical line colonization or a low-grade hypersensitivity reaction to the catheter material was responsible. Of note, serum IgE was raised at the time of significant pyrexia. PICC-related blood stream infections have a relatively low incidence in patients without cancer, 2.6 per 1000 catheter days [9]. However, it is worth noting that in a cohort of patients with cancer with suspected line infections, only 13% had positive line cultures, raising the possibility that this patient (who was established on antibiotics) had a culture-negative infection [10]. This is less likely given the repeated negative cultures of catheter tips that were removed.

Despite some diagnostic uncertainty, this case presents the most likely differential on the basis of a lack of significant clinical findings and radiographic evidence (an unremarkable CT–PET). It serves as a consideration to the wider clinical community to consider a reaction to the line itself in the absence of other convincing signs of infection. Although PICC lines are frequently used and usually very well tolerated, atypical reactions are noted in literature. This case underscores the importance of considering PICC-related complications in the differential diagnosis of unexplained fever, even in the absence of classic features of infection or thrombosis.

This case contributes to a growing body of literature suggesting that PICC lines, while generally safe, can be associated with a broader range of complications than commonly appreciated. Clinicians should maintain a high index of suspicion for line-related phenomena in patients with indwelling devices who present with unexplained systemic symptoms. In selected cases, a trial of removal of the PICC line may be both diagnostic and therapeutic.

Conclusion

This is a rare and unusual case, not previously cited in literature. The most likely diagnosis was initially felt to be a line infection or possibly drug-induced fever; however, persistence of symptoms despite different lines, cultures being negative, and cessation of fever with removal of the PICC line makes these differentials less likely. The authors therefore present the first case cited in literature of persistent fever secondary to PICC lines themselves. In cases such as this, patients require a thorough work-up with input from multiple specialties before such a diagnosis can be made.

Author contributions

The authors state equal contribution in the elaboration of this manuscript

Funding

CvH and BHLH would like to thank the Orthogeriatric Research Fund.

Data availability

Not applicable.

Declarations

Ethics approval and consent to participate

Ethics approval was not required.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

Not applicable.