Outpatient parenteral antimicrobial therapy (OPAT) from an emergency model applied during the COVID-19 pandemic to standard of care: Preliminary lessons from our experience

Abstract

Objectives

We wish to report on our experience of OPAT during the first two years of the COVID19 outbreak.

Patients and methods

We recorded data on all patients treated in the OPAT regimen in 2020 and 2021 and compared overall trends, use of carbapenems and saved days of hospitalization.

Results

The OPAT model enabled us to ensure the administration of first choice antibiotic therapy to 239 patients with an increase of 21.3% from 2020 to 2021 (108 vs 131). Applying this model, we also recorded a reduction in the use of carbapenems from 33% in 2020 to 26% in 2021 and a total of 3041 recovery days saved in 2021.The clinical cure rate reached 94%. Few adverse events occurred (35/239; 14.6%), and they did not require hospitalization.

Conclusion

OPAT is a safe, efficacious, and cost-effective model that functioned effectively during the COVID-19 crisis and could become the standard of care for the treatment of selected patients.

The COVID19 pandemic has had a huge clinical, social, psychological, and economic impact on the entire world population. Since the first case was diagnosed in our country in 2020 and during subsequent pandemic waves, the Italian health system experienced phases during which 30 % to 100 % of the beds in ordinary and intensive care units were occupied by patients with SARS-CoV-2 infection [1], [2]. As a result, many other pathologies went onto the “back burner” (low priority), occasioning an accumulation of more or less serious diagnostic and therapeutic delays. This experience has brought to light a key drawback of our healthcare systems, which are excessively hospital-based, with poor territorial medical coverage. Given the occupation of practically all beds by COVID19 patients, many outpatient facilities found it exceptionally difficult to care patients with complex diseases usually treated in hospital wards. They were suffering from infectious diseases other than COVID19 such as bacterial infections of the heart, bone, skin and soft tissues, the sensory organs, and the central nervous system. In order to treat patients with mild and severe infections in an emergency context of unavailability of hospital beds, our outpatient infectious disease center imported a health care model already applied in countries such as the UK, the USA, Belgium, Portugal, Netherlands, and Switzerland known as OPAT (Outpatient Parenteral Antimicrobial Therapy) [3], [4], [5], [6]. There exist three main models of OPAT according to whether antibiotic therapy is administered directly at the patient’s home (either by the patient himself or by a caregiver), at a dedicated infusion center, or in nursing facilities [7].

Under the supervision of the infectious disease department of our third-level university hospital, during 2020–2021 and in accordance with the OPAT model we treated 239 patients, with an increase of 21.3 % from 2020 to 2021 (108 vs 131). Demographic and clinical patient characteristics, types of infection treated and antibiotics used are shown in Table 1 . Patients entered the unit from our polyclinic (or referred by their general practitioners) following an initial period of hospitalization and an initial evaluation by an infectious disease specialist at our clinic. Patients were admitted to the OPAT protocol after assessment of their adherence to the proposed program, caregiver or social support, the characteristics of their infectious disease (clinical stability, antibiotic sensitivity of the pathogen) and the characteristics of the antibiotic drug (chemical stability, practical administration scheme, compatibility with the patient’s venous access and with the infusion device chosen). Follow-up was conducted to monitor response to treatment, any adverse effects related to the drug, venous access, or complications of the infectious disease, and to establish the exact timing of therapy or make any changes to treatment. Treatment of the patients required different specialists (physician, infectious disease specialist, vascular access teams, specialized nurses, pharmacists) who together constituted the OPAT team [7], [8]. Patients having received antimicrobial therapy through elastomeric pumps were 19/108 in 2020 and 28/131 in 2021 (18 % vs 21 %, +3%). Patients having received treatments with ertapenem, considered as an indicator of carbapenem use, were 36/108 in 2020 and 34/131 in 2021 (33 % vs 26 %; −7%) as shown in Fig. 1 . These data, in line with the shared intention to implement carbapenem-sparing policies, illustrate the introduction in care settings of therapeutic administration models such as infusion pumps, which enable the use of active antibiotics against extended-spectrum beta-lactamase-producing species (e.g., piperacillin/tazobactam or cefepime according to antibiogram). Taken together with other forms of antibiotic stewardship including once-daily administration of ertapenem, they helped to reduce the use of other carbapenems, which are often chosen as the only possibility for outpatient treatment of infections sustained by multi-drug resistant organisms (MDROs). Preliminary statistical analysis of our data shows that in 2021, the cumulative duration of treatments for all patients averaged 3041 days. This figure has major economic significance when considered as an indicator of saved recovery days; more precisely, given that (according to a report by the Italian ministry of economy) a day of hospital stay in Italy has an average per capita cost of $650, the healthcare expenditures avoided amount to about 2 million dollars [9]. Moreover, none of the patients required new hospitalization for the same pathology within thirty days from the end of the antibiotic therapy, and the clinical cure rate was 94 %. Among 239 patients, 11 (4.6 %) experienced recurrence of infection within 30 days. In line with other studies, most of the registered adverse events were defined as minor since none of them required hospitalization and could be dealt with in the same OPAT setting [10]. These events were venous access-related (thrombosis [12/239] 5 %) and antibiotic-related (rash and itch [5/239] 2 %, elevation in liver function test [5/239] 2 %, impaired renal function [10/239] 4 %, C. difficile infection [3/239] 1.3 %).

Table 1.

Demographic, clinical and therapeutic characteristics of 239 patients.

Characteristics	Value (n = )
Age in years, median (IQR) Male, n (%)	63 (20–91) 125 (52.3)
Underlying diseases, n (%) Solid malignancy Cardiovascular disease Diabetes mellitus Urological disease Immunosuppression Chronic lung disease Hematological malignancy	77 (32.0) 27 (11.5) 23 (9.9) 18 (7.6) 14 (6.1) 11 (4.6) 3 (1.5)
Infection types, n (%) Urinary tract infection Bloodstream infection Acute bacterial skin and skin structure infection Osteomyelitis Endocarditis Intra-abdominal infection Head and neck infection Pneumonia Leishmaniasis	57 (23.8 %) 43 (18.0 %) 32 (13.4 %) 29 (12.1 %) 22 (9.2 %) 21 (8.8 %) 14 (5.9 %) 14 (5.9 %) 7 (2.9 %)
Antimicrobial agents used, n (%) Ertapenem Daptomycin Ceftriaxone Piperacillin/Tazobactam Dalbavancin Teicoplanin Cefepime Liposomal Amphotericin B Amikacin Oxacillin Caspofungin Meropenem Colistin Ceftazidime Ceftazidime/Avibactam Acyclovir Fluconazole Gentamicin	68 (28.5) 35 (14.6) 33 (13.8) 20 (8.4) 19 (7.9) 13 (5.4) 8 (3.3) 7 (2.9) 7 (2.9) 7 (2.9) 5 (2.1) 5 (2.1) 3 (1.3) 3 (1.3) 2 (0.8) 2 (0.8) 1 (0.4) 1 (0.4)
Length of antimicrobial therapy (day), media Elastomeric pump therapy, n (%)	14 47 (19.7)

Fig. 1.

Patients treated in OPAT and percentage of those who received therapy with ertapenem per year.

As far as we know, ours is the largest Italian patient cohort to have received treatment according to the OPAT protocol. In conclusion, the OPAT model seems to be a valuable and promising public health tool in terms of cost optimization and treatment of many infectious diseases, as has been shown in studies having compared the costs of the OPAT model with those of hospital stay [11]. During 2020–2021, it proved to be a rescue strategy that prevented dozens of patients with infectious disease from being denied treatment because of the scarcity of available beds in hospital facilities. Many studies are still needed not only to better define target patient categories, implementation care settings and additional usable antibiotic molecules, but also to quantify and stratify adverse events related to the therapy administered in OPAT (often due to drug reactions or complications of venous access). However, OPAT may already be considered as a therapeutic option with a good cost-effective profile that could bring down the costs of hospital management of some infections, ensure greater adherence to antimicrobial stewardship campaigns through the savings of carbapenem therapies, and reduce multidrug-resistant organism infections by shortening patients’ residence time in healthcare environments where these pathogens are particularly widespread.

Ethical approval

All procedures performed in this study were in accordance with the 1964 Helsinki declaration and its later amendment. Moreover the protocol of this study has been approved on 11/11/2021 by the ethics committee of Fondazione Policlinico Gemelli with protocol number 4582.

CRediT authorship contribution statement

G. Giuliano: Data curation, Formal analysis, Investigation, Writing – original draft. F. Raffaelli: Data curation. D. Faliero: Investigation. E. Tamburrini: Conceptualization, Methodology, Data curation, Formal analysis, Investigation, Validation, Writing – review & editing. D. Tarantino: Resources. M.C. Nurchis: Conceptualization, Methodology. G. Scoppettuolo: Conceptualization, Methodology, Validation, Supervision.