Continuous Intravenous Acyclovir as Outpatient Parenteral Antimicrobial Therapy for HSV and VZV Neurological Infections: A Case Series With Pharmacokinetic and Cost Evaluation, and Review of Literature

ABSTRACT

Varicella zoster virus (VZV) and herpes simplex virus (HSV) are major causes of viral meningitis and encephalitis. Standard intermittent intravenous acyclovir requires hospitalisation, reducing patient comfort and prolonging admissions. Continuous infusion may maintain therapeutic plasma and cerebrospinal fluid (CSF) concentrations while enabling treatment through Outpatient Parenteral Antimicrobial Therapy (OPAT). Objectives to evaluate the feasibility, pharmacokinetic target attainment, and cost reduction of continuous intravenous acyclovir for HSV and VZV neurological infections in an OPAT setting. We conducted a case series of eight patients with HSV or VZV neurological infections who received continuous intravenous acyclovir through our OPAT programme after initial hospital‐based therapy. Steady‐state plasma concentrations were measured to assess pharmacokinetic target attainment. Costs were calculated based on daily costs of discontinued inpatient care and OPAT. Existing literature on continuous intravenous acyclovir and acyclovir in OPAT was reviewed. No persistent complications associated with continuous intravenous acyclovir administration were observed. All patients completed treatment with good clinical responses; one had persistent ptosis, and another developed postherpetic neuralgia. Acyclovir plasma concentrations remained above the therapeutic threshold in all seven measured cases, suggesting adequate CSF exposure. Hospital admissions were shortened, with no readmissions. The acyclovir OPAT programme led to cost savings of 3486 EUR per patient. Despite this small case series, continuous intravenous acyclovir appears to be feasible for treating HSV and VZV neurological infections in an OPAT setting, with potential benefits in patient comfort, healthcare costs, and hospital resource utilization. Larger studies are warranted to assess safety and efficacy.

Abbreviations

AIDS

acquired immunodeficiency syndrome

CRRT

continuous renal replacement therapy

CSF

cerebrospinal fluid

ECLS

extracorporeal life support

eGFR

estimated glomerular filtration rate

GvHD

graft versus host disease

HSCT

hematopoietic stem cell transplantation

HSV

Herpes Simplex Virus

HZO

Herpes Zoster Ophthalmicus

iv

intravenous

long COVID

post‐acute sequelae of SARS‐CoV‐2 infection

NA

not available

OPAT

outpatient parenteral antimicrobial therapy

PCR

Polymerase Chain Reaction

PICC

peripherally inserted central catheter

TDM

therapeutic drug monitoring

VZV

Varicella Zoster Virus

WAS

Wiskott‐Aldrich syndrome

1. Introduction

Varicella zoster virus (VZV) and herpes simplex virus (HSV) are globally among the most frequent viral causes of severe infections, such as encephalitis and meningitis [1, 2]. VZV may also manifest as herpes zoster ophthalmicus (HZO). Standard therapy consists of intravenous (iv) acyclovir 10 mg/kg three times daily for 7–10 days in HZO and 10–21 days in meningitis or encephalitis [3, 4]. This frequent dosing schedule typically requires hospitalisation, even when patients are clinically stable, affecting patient comfort [5, 6], hospital capacity, and increased healthcare costs [7]. Several studies have demonstrated the safety, efficacy and benefits of Outpatient Parenteral Antimicrobial Therapy (OPAT) [6, 7, 8, 9]. OPAT contributes to antimicrobial stewardship through optimising antimicrobial selection, dosing and duration [8], while potentially reducing the risk of nosocomial and peripherally inserted central catheter (PICC) infections, compared to inpatient care [6, 7]. However, most OPAT studies have focused on antibiotic therapy, data on antiviral treatment, such as acyclovir, remain scarce.

Important considerations for making acyclovir suitable for OPAT include feasibility of continuous infusion and drug stability. Acyclovir diluted in 0.9% saline is stable for at least 7 days at room temperature at concentrations ≤ 10 mg/mL, making it well‐suited for OPAT [10, 11].

Acyclovir efficacy is time‐dependent and requires plasma concentrations above the IC₅₀ (approximately 0.56 mg/L for HSV, and 1.125 mg/L for VZV) [12, 13, 14] for more than 50% of the dosing interval. Continuous iv acyclovir administration is expected to maintain concentrations consistently above the inhibitory threshold, thereby likely optimising antiviral efficacy [12]. A pharmacokinetic diagram of continuous versus intermittent acyclovir administration is shown in Supporting Information S1: Figure S1. For neurological infections, cerebrospinal fluid (CSF)/plasma ratio of approximately 50% should be considered [15], therefore, plasma concentrations > 2.25 mg/L are expected to achieve therapeutic CSF levels.

Several case reports suggested benefits of continuous iv acyclovir over intermittent dosing in severe or resistant HSV or VZV infections, particularly in hospitalised immunocompromised patients [16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28]. However, only three reports describe home‐based continuous iv acyclovir therapy in two neonates with HSV‐2 encephalitis [29], and two adults with HSV proctitis [16], and one adult with cutaneous VZV [27]. To the best of our knowledge, this is the first report of neurological viral infections in adults treated with continuous iv acyclovir in OPAT setting. We describe eight HSV or VZV cases managed via OPAT, including steady‐state pharmacokinetic assessment of continuous acyclovir, hospital cost analysis, alongside a review of existing literature.

2. Methods

This case series was approved by the Institutional Review Board of Spaarne Gasthuis Hospital (ACLU 2025.0116). Between July 2024 and July 2026, OPAT‐eligible patients receiving acyclovir provided written consent. Clinical data were extracted from electronic health (EPIC) and laboratory (GLIMS) records. A good response was defined as clearance of complaints. Recurrences and readmissions were evaluated during 1‐month follow‐up period after cessation of antiviral therapy. Plasma acyclovir concentrations were measured by validated LC‐MS/MS, and HSV/VZV PCR assays were performed using the Panther Fusion system. Both analyses were conducted in ISO15189‐accredited laboratories. A pharmacokinetic diagram was made using MWPharm++ (Figure S1). A systematic literature search on continuous acyclovir use and acyclovir in OPAT was conducted on August 5th, 2026, followed by a narrative synthesis of the available evidence. Databases PubMed, TRIP, and the Cochrane Library were searched using the terms ‘OPAT’, ‘Outpatient Parenteral Antimicrobial Therapy’, ‘outpatient’, ‘continuous’, ‘ambulatory’, AND ‘acyclovir’ or ‘aciclovir’. Studies published in English or Dutch were eligible for inclusion. One relevant article was found in Japanese, which was not available in full text. Reference lists of relevant articles were screened. The PRISMA flow diagram of the literature search is presented in Supporting Information S1: Figure S2. Cost data were obtained from hospital administrative sources. Inpatient costs were estimated using the average daily admission price and subtracted from OPAT costs to account for reduced hospital days. OPAT‐related costs included iv acyclovir preparation, PICC placement, therapeutic drug monitoring (TDM), and OPAT team expenses. Costs were inflation‐adjusted to 2025 and 2026 values [30, 31]. Costs were calculated as means per patient and total costs. Only direct hospital and pharmacy costs were included (Supporting Information S1: Table S1).

OPAT protocol (Supporting Information S1: Figure S3): The OPAT team assesses the indication for OPAT, and the patient's suitability for treatment at home, and provides recommendations on continuous acyclovir therapy, including the appropriate dosage, and laboratory monitoring. Following PICC placement by the interventional radiologist, and organization of home care, and preparation of acyclovir pumps by the compounding pharmacy, patients are discharged to complete treatment at home. In the OPAT programme, a home healthcare nurse visits the patient once daily to connect the 24‐h acyclovir infusion. In the self‐administered OPAT (S‐OPAT) programme [32], patients receive structured training to independently manage the infusion. In both OPAT and S‐OPAT, the home healthcare team remains available to provide support and assistance in the event of technical, medical, or treatment‐related problems, for weekly PICC line care, and removal of the PICC upon completion of antimicrobial therapy. Medical follow‐up, including clinical assessment and laboratory monitoring, is performed by the treating physician during scheduled outpatient visits.

2.1. Patients

This case series includes eight patients (seven women, one man; 16–80 years) with HSV or VZV neurological infections. None of these patients received prior VZV vaccination. All patients initially received iv acyclovir 10 mg/kg three times daily. During hospitalisation or at discharge, treatment was switched to continuous infusion of 30 mg/kg/day (≤ 10 mg/mL in 0.9% saline). Therapy was continued via OPAT in six patients, administered by outpatient care nurses through a PICC using an infusion pump. For two patients, the outpatient care nurses taught the patient how to administer the acyclovir themselves. In these S‐OPAT patients, a PICC with extension line was used, and acyclovir was prepared in an elastomeric pump. Individual acyclovir treatment timelines are shown in Figure 1.

FIGURE 1.

Individual acyclovir treatment timeline.

All patients presented with severe headaches to neurology, internal medicine, or paediatric emergency departments. Additional clinical features varied (Table 1).

TABLE 1.

(Baseline) characteristics.

	Case A	Case B	Case C	Case D	Case E	Case F	Case G	Case H
Sex	Female	Female	Female	Male	Female	Female	Female	Female
Age (years)	16	35	77	78	78	48	21	80
Weight (kg)	54.4	75	60	89	81.5	91	69	72.5
Prior history	Previously healthy	Migraine, endometriosis	Transient ischaemic attack	Previously healthy	Hypertension, retinal venous occlusion	Rheumatoid arthritis without medication, long COVID	Migraine	Hypertension, gout, asthma, OSAS
Diagnosis	VZV encephalitis	VZV meningitis	VZV meningitis	HZO	VZV encephalitis	HSV‐1 meningitis	HSV‐2 meningitis	VZV encephalitis
Cerebrospinal fluid
— Leucocytes (< 5 cells/ul)	156	35	169	NA	5	386	1402	409
— Polymorphonuclear (%)	1	100	2	NA	NA	3	95	99
— Monomorphonuclear (%)	99	0	98	NA	NA	97	5	1
— Protein (262–790 mg/L)	220	510	1800	NA	540	1820	1190	1380
— Glucose (2.5–3.7 mmol/L)	2.5	3.0	1.8	NA	3.4	2.5	3.3	3.3
Serum glucose (mmol/L)	7.2	5.2	5.0	NA	5.5	5.9	7.5	6.2
Cerebrospinal fluid HSV/VZV PCR (cycle time)	VZV positive (39.6)	VZV and HSV negative	VZV positive (29.9)	NA	VZV positive (35.1)	HSV positive (type 1: 33.1)	HSV positive (type 2: 20.0)	VZV positive (34.7)
Duration in‐hospital intermittent acyclovir (days)	6	4	3	2	0	14	6	4
Duration in‐hospital continuous iv acyclovir (days)	1	2	4	5	8	5	0	0
Duration of continuous iv acyclovir in OPAT (days)	7	5	7	11	2	2	8	10
Total therapy duration (days)	14	11	14	18	10	21	14	14
Waiting for discharge (days)	4	1	4	5	5	4	2	2
Steady‐state plasma acyclovir level (mg/L)	2.9	2.9	5.1	6.4	8.1	c Plasma: 43.4 CSF: 2.5	6.1	NA
eGFR (mL/min/1.73 m2)
— Before start	b > 90	> 90	78	79	58	76	> 90	66
— During acyclovir	b > 90	> 90	79	81	80	a 25	> 90	65
— After acyclovir	NA	NA	82	82	73	76	NA	NA
Complications/adverse events/readmissions/recurrences	None	None	None	None	None	None	None	None
Clinical response	Good	Good	Good	Persistent ptosis	Postherpetic neuralgia	Good	Good	Good

Abbreviations: CSF = cerebrospinal fluid; eGFR = estimated glomerular filtration rate (normal level adults: > 60 mL/min/1.73 m²); HSV = Herpes Simplex Virus; HZO = Herpes Zoster Ophthalmicus; long COVID = post‐acute sequelae of SARS‐CoV‐2 infection; NA = not available; OPAT = Outpatient parenteral antimicrobial therapy; OSAS = obstructive sleep apnoea syndrome; PCR = Polymerase Chain Reaction; VZV = Varicella Zoster Virus.

^a Interpreted as prerenal acute kidney injury, fully normalised after saline therapy.

^b Calculated using Schwartz formula [33].

^c Outlier due to sampling directly from PICC

Cases A, E, F, and H additionally reported confusion, bradyphrenia, and nausea. Case A, F, and G also had photophobia/phonophobia, whereas CSF pressure was elevated in A. Case E presented with fever and vesicular lesions around her right eye. Cases A, E, and H were diagnosed with VZV encephalitis, and cases F and G with HSV‐1, respectively HSV‐2 meningitis.

Cases B, C and G presented with headache, nausea, and vesicular skin lesions on the face, left chest, and genital region respectively. Cases B and G had fever, neck stiffness, and case B also had altered consciousness, while C reported visual disturbances. Both cases B and C were diagnosed with VZV meningitis, although CSF PCR was negative in case B.

Case D presented with HZO including vesicular lesions, impaired ocular motility, and ptosis. The diagnosis of HZO due to VZV infection was made on clinical grounds. Diagnoses in other cases were confirmed by PCR (Table 1).

Patients A, B, C, D, E, and G demonstrated adequate plasma acyclovir levels of 2.9–8.1 mg/L during continuous infusion. Case F showed an abnormally high level of 43.4 mg/L in plasma, likely resulting from sampling directly from the PICC, causing contamination from residual acyclovir in the catheter lumen. In CSF of patient F, the acyclovir level was 2.5 mg/L, which is in line with our hypothesis that the high plasma level was due to sampling from the PICC.

In patient H, acyclovir steady state plasma concentration was not available.

Case F developed transient prerenal acute kidney injury due to vomiting and reduced intake. Acyclovir was temporarily reduced to 20 mg/kg/day without interruption, and renal function normalised rapidly after iv fluids, with no leukocyturia or haematuria.

Cases A, B, C, F, G, and H recovered fully, while D and E experienced ptosis and postherpetic pain, respectively. No adverse events, persistent acyclovir‐related complications, recurrences, or readmissions occurred.

2.2. Costs

Table 2 summarises costs and savings of the acyclovir OPAT programme. Outpatient care reduced costs, while TDM, PICC placement, and OPAT team expenses increased them. Overall, OPAT saved 3486 EUR per patient, mainly from a 6.5‐day shorter mean hospital stay. Mean in‐hospital waiting time before discharge was 3.4 days. Reducing this to one day could save an additional 1775 EUR per patient.

TABLE 2.

Overview of costs and savings.

	Mean costs per patient	Mean savings per patient	Total costs all patients (n = 8)	Total savings all patients (n = 8)
Outpatient iv preparations of acyclovir	1148.80		9190.37
OPAT team	24.29		194.33
TDM	7.25		57.97
PICC placements	233.30		1866.43
Outpatient days a		4899.75		39,197.96
Total savings		3486.11		27,888,86

Note: All amounts are reported in euros (EUR). Bold values are total savings.

Abbreviations: OPAT = outpatient parenteral antimicrobial therapy; PICC = peripherally inserted central catheter; TDM = therapeutic drug monitoring.

^a Based on the average daily costs of admission to the internal medicine department, which were avoided through OPAT.

3. Discussion

This case series suggests that continuous iv acyclovir in an OPAT setting is feasible, and well tolerated in patients with HSV and VZV neurological infections. From an antimicrobial stewardship perspective, continuous iv acyclovir through OPAT may support optimization of antiviral therapy by enabling appropriate dosing and treatment duration while avoiding unnecessary hospitalisation. This approach may reduce healthcare resource utilization without compromising treatment continuity. No major safety concerns were observed in this small cohort. Although considerable variability was observed among the eight patients, no virological relapses or persistent acyclovir‐related complications were observed. All patients with available measurements achieved therapeutic steady‐state plasma concentrations > 2.25 mg/L, the level considered adequate for antiviral activity in the central nervous system [12, 13, 14, 15].

Furthermore, home‐based treatment reduced length of hospital stay. All patients completed therapy at home with favourable outcomes. However, one patient had persistent ptosis and another developed postherpetic neuralgia, a common complication of VZV, particularly in patients with ophthalmic involvement [34], as exemplified by case E.

Besides patients with HSV and VZV meningoencephalitis and HZO described in this case series, continuous acyclovir administration may also be considered in other patient groups requiring iv acyclovir, such as patients with varicella vaccine‐associated meningoencephalitis following live‐attenuated VZV vaccination. Although live‐attenuated VZV vaccination is not yet routine in the Netherlands, its increasing global use may lead to more cases [35, 36].

Continuous administration of antimicrobial therapy in outpatient setting offers several advantages, including improved patient comfort and quality of life by allowing recovery at home [5, 6], and reduced hospital burden and healthcare costs [7, 8, 37]. Rolston et al. reported on 38 immunocompromised patients receiving three times daily ambulatory acyclovir [38], which is often logistically unfeasible. Continuous infusion overcomes this, requiring only a once‐daily home‐care visit.

Moreover, continuous administration maintains drug concentrations above the IC₅₀ throughout the dosing interval, in contrast to intermittent dosing, and may therefore optimise antiviral efficacy [18, 22]. If acyclovir plasma concentrations were readily available, they could potentially facilitate therapeutic drug monitoring, allowing for individualised dose optimization and antimicrobial stewardship.

These pharmacokinetic considerations are also relevant when considering oral valacyclovir as an alternative for CNS HSV or VZV infections. Although high‐dose oral valacyclovir can achieve systemic acyclovir exposure approaching that of intravenous acyclovir [39], antiviral efficacy depends on maintaining acyclovir concentrations above the IC₅₀ for a sufficient proportion of the dosing interval [12]. Based on the reported pharmacokinetic properties of valacyclovir (e.g., C _max, t _max, t _1/2) [39], acyclovir concentrations may fall below the IC₅₀ approximately 5.8 hours following oral valaciclovir administration in a 70‐kg patient with normal renal function. Given the limited clinical evidence for oral valacyclovir, and the uncertainty regarding adequate CNS exposure and time above the IC₅₀, particularly in VZV CNS infections, intravenous acyclovir remains the preferred treatment [4].

Table 3 summarises the published literature on continuous acyclovir administration and the use of acyclovir in an OPAT setting.

TABLE 3.

Previous reports on continuous acyclovir and/or acyclovir in OPAT.

Article	Studie design	n	Age (years)	Immuno deficient	OPAT	Dosage acyclovir (mg/kg/day)	Acyclovir steady state plasma concentration (mg/L)	Duration continuous acyclovir (weeks)	Type of infection	Underlying disease	Outcome	Adverse events/residual symptoms
O'Leary et al. (2020) [29]	Case series and review	2	0	No	Yes	60	2.1–8	2–2.5	HSV‐2 encephalitis	None	Cured	Nil
Ikawa et al. (2019) [18]	Case report	1	10	Yes	No	30	NA	6	HSV‐1 oral mucositis	Leukaemia, HSCT	Cured	Nil
Cies et al. (2015) [25]	Case report	1	0	No	No	5.5 mg/L dialysate	5.3–8.8	0.5	Disseminated neonatal HSV‐1	ECLS, CRRT	Unrelated death	NA
Rolston et al. (2014) [38]	Prospective cohort	38	17–71	Yes	Yes	q8h 500 mg/m2	NA	0.5–2	Cutaneous VZV	38 malignancy, 9 HSCT	87% response	2 AKI; 2 progression; 7 iv access problem
Kim et al. (2011) [20]	Case series	6	37–55	Yes	No	30–45	NA	2–16	4 HSV‐1 oro‐pharyngitis, 2 genital HSV‐2	HSCT, GvHD	5 resolved, 1 partially resolved	Nil
Kakisaka et al. (2009) [19]	Case report	1	0	No	No	48	NA	1	HSV‐2 encephalitis	None	HSV‐2 PCR negative in CSF	Nil
Kakinuma et al. (1997) [21]	Case report	1	40	Yes	No	48	NA	2	Generalised VZV	Leukaemia	Resolution lesions	Nil
Inoue et al. (1996) b [28],	Case report	1	NA	Yes	NA	NA	NA	NA	HSV‐1	WAS	Improved	NA
Modiano et al. (1995) [26]	Case report	1	28	Yes	No	45	NA	NA	Facial HSV‐1	WAS, B‐cell lymphoma	Cured	NA
Mock et al. (1994) [17]	Case report	1	32	Yes	No	50	NA	NA	Genital HSV	Hodgkin lymphoma	5 cured, 1 unrelated death	NA
Baxter et al. (1994) [27]	Case report	1	19	Yes	Yes	15–30	NA	9	Disseminated cutaneous VZV	Lymphoma	Death due to underlying disease	Several relapses
Engel et al. (1990) [16]	Case series	2	26–57	Yes	Yes	36–48	4.5–6.75	6	HSV‐2 proctitis	AIDS	Cured	Nil
Fletcher et al. (1989) [22]	Case series	13	2–57	Yes	No	29–150	4.5–22	1–7	3 HSV; 6 CMV; 4 EBV	a 2 AIDS, 1 WAS, HSCT	a Cured	3 neutropaenia
Bean et al. (1987) [24]	Case report	1	8	Yes	No	125 mg/h (weight NA)	9.0–10.3	2	HSV‐1 mucocutaneous, keratitis	WAS, HSCT	Resolution lesions, recurrence in 1 week	Nil
Alexander et al. (1987) [40]	RCT	30	21–58	No, except for 1	No	45	NA	28	Hepatitis B	12 liver disease, 1 AIDS	4 serocon‐ version	30 phlebitis, 2 haematuria
Spector et al. (1982) [23]	Prospective cohort	16	16–77	Yes	No	7–43	0.9–8.2	3–5 days	14 VZV; 2 HSV skin lesions	14 haematological malignancy, 2 solid malignancy	Resolution lesions	3 postherpetic pain

Abbreviations: AIDS = acquired immunodeficiency syndrome; CRRT = continuous renal replacement therapy; ECLS = extracorporeal life support; GvHD = graft versus host disease; HSCT = hematopoietic stem cell transplantation; HSV = herpes simplex virus; NA = Not available; OPAT = outpatient parenteral antimicrobial therapy; VZV = varicella zoster virus; WAS = Wiskott‐Aldrich syndrome.

^a In HSV or VZV patients.

^b Full report not available, written in Japanese.

Although mostly not in an OPAT setting, several case reports have demonstrated the potential benefits of continuous iv acyclovir for severe or refractory HSV and VZV infections, particularly in immunocompromised patients [16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29]. Among these 48 patients (age range 0–77 years) who received continuous iv acyclovir, the majority (44/48) were immunocompromised [16, 17, 18, 20, 21, 22, 23, 24, 26, 27, 28], reflecting the underlying risk profile. VZV infection was observed in 16 patients [21, 23, 27], HSV‐1 in 9 [18, 20, 24, 25, 26, 28], HSV‐2 in 8 [16, 17, 19, 20, 29], while HSV infection was not further specified in 5 patients [22, 23]. The remaining 10 patients had cytomegalovirus or Epstein‐Barr virus infection [22]. One clinical trial investigated continuous acyclovir administration in 30 patients with hepatitis B, but no therapeutic benefit was observed in this population [40]. Considering only patients with HSV and VZV infections in these reports, all presented with mucocutaneous lesions [16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 29], four were neonates who also had disseminated HSV disease [19, 25, 29]. Resolution of infection occurred in 33 patients (87%). One patient had a partial response [20], another had a recurrence within a week of stopping acyclovir therapy [24]. Three patients died during therapy of unrelated causes or underlying disease [17, 25, 27].

In our case series, continuous acyclovir was administered at 30 mg/kg/day, which falls within the range reported in previous reports (30–60 mg/kg/day) [16, 17, 18, 19, 20, 21, 23, 26, 27, 29, 40]. However, as none of these reports describe adult patients with viral neurological infections similar to the eight immunocompetent cases in our series, compatibility remains limited.

Case F developed transient prerenal acute kidney injury, likely due to vomiting and reduced oral intake, known risk factors for acyclovir‐induced nephrotoxicity [41, 42]. No leukocyturia or haematuria was observed, indicating absence of crystalluria [42]. This highlights the importance of managing dehydration, and renal function‐adjusted dosing to prevent acyclovir‐related renal complications [42, 43]. Continuous iv acyclovir may further reduce nephrotoxicity and other peak‐related adverse effects, such as neurotoxicity and neutropenia, by maintaining stable plasma concentrations and minimising tubular crystal formation [41, 42, 43].

The acyclovir OPAT programme saved 3486 EUR per patient, potentially rising to approximately 5261 EUR with optimised outpatient services. Previous studies have reported reduced healthcare costs with OPAT [7, 8, 37], consistent with our findings. While not directly quantified in our study, OPAT also provides additional economic benefits by shifting care from hospital to home [7]. This emphasises the importance of coordinated collaboration among all healthcare providers.

Nevertheless, limitations must be acknowledged. This small case series lacked a control group, preventing conclusions on comparative efficacy versus intermittent dosing. CSF acyclovir concentrations are rarely measured in clinical practice because serial lumbar punctures during treatment are not routinely performed in the Netherlands. Consequently, direct assessment of CSF exposure is challenging, therefore exposure was estimated based on plasma concentrations and published plasma‐to‐CSF ratios [15], as direct CSF measurements were unavailable for most patients. The applicability of these ratios to all individuals remains uncertain due to potential interpatient variability in CNS penetration. No small children were included. In addition, robust clinical evidence for acyclovir in HZO is limited [44], and the HZO patient in this case series had persistent residual symptoms, consistent with long‐term sequelae reported in around 4% of cases [45]. Also, long‐term outcomes are unknown in two patients. Furthermore, only hospital‐related costs were included in our analyses, as home‐care costs, patient productivity, and broader societal costs were not included. Given the real‐world setting and retrospective study design, neurological functional scores, neuroimaging, CSF analyses, and quality‐of‐life assessments could not be systematically collected during follow‐up. Future prospective studies in larger cohorts are needed to confirm these observations.

4. Conclusions

In conclusion, continuous iv acyclovir appears to be a promising strategy for treating HSV and VZV neurological infections in an OPAT setting. Although limited to a small case series, this study provides valuable insight, as outpatient continuous acyclovir administration has not previously been reported in this patient population. If confirmed in larger studies, continuous infusion could provide a feasible and cost‐saving alternative to intermittent in‐hospital treatment.

Author Contributions

I.G.M. an E.L.T. directly accessed, verified, and extracted underlying data reported in the manuscript. I.G.M., E.L.T. and K.H.H. did the literature search. I.G.M. and E.L.T. wrote and revised the manuscript. All authors had full access to all data, interpreted the data, revised the manuscript and approved the final version, and agreed to be accountable for the work. I.G.M. and E.L.T. contributed equally.

Funding

The authors have nothing to report.

Ethics Statement

This case series was approved by the Institutional Review Board of Spaarne Gasthuis Hospital (ACLU 2025.0116).

Consent

All patients provided written consent.

Conflicts of Interest

The authors declare no conflicts of interest.

Permission to Reproduce Material From Other Sources

The authors have nothing to report.

Supporting information

Supporting Information S1

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.