From November 2018 - September 2022 353 patients were assigned to the OPAT program. Multiple assignments to the OPAT program were possible; this is why we report “episodes” in this publication and not “patients”. Of these 353 assignments, the patients of 303 episodes gave written informed consent and were included in the current analysis (Figure 1).
3.1 Baseline characteristics
Table 1 summarizes patient characteristics. Most patients were male (n=173; 67%) and the median age was 57 years (range 18-92). The majority had a single OPAT episode, but 22 patients had multiple episodes. OPAT indications included 71 individual diagnoses, whereby urogenital, endovascular and osteoarticular infections constituted the main part of infections. Accordingly, Gram-negative bacteria (Enterobacterales n=103; P. aeruginosa n=38), Staphylococcus aureus (n=35), Coagulase-negative Staphylococci (n=21) and Streptococcus spp (n=17) predominated. About one-fifth of infections were polymicrobial (21%). Another important reason for OPAT was neurosyphilis (n=15). The patients were referred to the program from over 26 hospital specialties. The most common antimicrobial agents included β-Lactam antibiotics (n=197), followed by glycopeptides (n=24).
Table 1. Characteristics of the patients and their treatment
Characteristics
|
OPAT episodes
n=260
|
Female sex, n (%)
|
87 (34)
|
Age, median years (range)
|
57 (18-92)
|
BMI, median kg/m2 (range)
|
25 (16-53)
|
Charlson comorbidity index, median (range)
|
3 (0-13)
|
Indication for OPAT (stratified by ICD-10 codes) n (%)
|
|
Urinary tract infections
|
78 (30)
|
Foreign body associated infections (osteoarticular or vascular
devices); including:
|
39 (15)
|
Prosthetic joint infections (n=16)
Others (n= 9)
Vascular graft infections (n=12)
Mamma prosthesis (n=2)
|
|
Osteoarticular infections
|
22 (8.5)
|
Central nervous system infections; including:
|
23 (8.8)
|
Neurosyphilis (n=15)
|
|
Intraabdominal infections
|
3 (1.2)
|
Metabolic organs (bile, liver, etc.)
|
17 (6.5)
|
Infective endocarditis
|
14 (5.4)
|
Respiratory tract infections
|
9 (3.5)
|
Ear, nose and throat infections
|
5 (1.9)
|
Other and unspecific infections and parasitic diseases; including:
|
50 (19.2)
|
Bloodstream infections (n=31)
|
|
Antimicrobial substance used (mode of administration) n (%)
|
|
Aminoglycosides
|
6 (2.2)
|
Antivirals
|
2 (0.77)
|
Antifungals
β-lactams
|
1 (0.38)
|
Cefepim (continuous)
|
27 (10)
|
Cefiderocol (intermittent)
|
1 (0.38)
|
Ceftazidim (intermittent)
|
2 (0.76)
|
Ceftazidim/Avibactam (intermittent or continuous)
|
3 (1.1)
|
Ceftriaxon (intermittent)
|
48 (18)
|
Ertapenem (intermittent)
|
57 (22)
|
Flucloxacillin (continuous)
|
26 (10)
|
Meropenem (intermittent)
|
8 (3)
|
Penicillin G (continuous)
|
22 (8)
|
Piperacillin/Tazobactam (continuous)
|
66 (12)
|
Glycopeptides (intermittent)
|
24 (9.2)
|
Vascular access, n (%)
|
|
PICC-line or Port
|
195 (73)
|
PVC
|
70 (27)
|
Notes: An OPAT episode may have consisted of the administration of multiple antimicrobials simultaneously. Patients were allowed to be included several times in this study, by this, the data is presented as number of episodes.
Abbreviations: Outpatient parenteral antimicrobial therapy, OPAT; Peripherally inserted central catheter, PICC; Peripheral venous catheter, PVC; body mass index, BMI
Most of the antimicrobials used were administered intermittently, for which no special device was needed (n=158), the other 102 OPAT episodes consisted of at least one antibiotic that was infused continuously (Table 2).
Table 2. Mode of administration of OPAT antibiotic and duration.
OPAT device
|
OPAT episodes
n (%)
|
OPAT duration
median days (IQR)
|
Total days of OPAT
|
Intermittent infusion (no device)
|
158 (61)
|
8 (5-15)
|
2077
|
Continuous infusion (elastomeric pump)
|
87 (33)
|
13 (8-26)
|
1483
|
Continuous infusion (battery-operated pump)
|
15 (5.8)
|
21 (9-32)
|
374
|
Overall
|
260 (100)
|
10 (6-21)
|
3934
|
Abbreviations: Outpatient parenteral antimicrobial therapy, OPAT
The median OPAT duration consisting of continuous infusion was longer than the duration of OPAT consisting of intermittent infusion.
3.2 ABS
In 20 cases, OPAT was declined due to a possible switch from the parenteral to the oral treatment form. In additional 23 cases, the OPAT team decided together with the patient and his care team that OPAT was not suitable for the patient or the patient decided against OPAT.
In 18 of the remaining 260 OPAT episodes, the choice of the antimicrobial treatment was adjusted and in another 6 episodes, the length of therapy was optimized (shortened n=2, lengthened n=4). Moreover, OPAT led to a significant alteration of patient assessment including recognition of additional testing (n=141), source control (n=94), allergy testing (n=16), update of vaccine status (n=16), recognition of a non-urgent medical problem (n=33), transition of care (n=247; including identification of psychosocial problems influencing treatment among 33 patients) and follow-up (intravenous (IV) to oral switch after OPAT, n=50; management of line-related events or ADE in follow up visits n=46). Hence, led by ABS strategies, patient care was optimized in 247 out of 260 OPAT episodes (95%) (Figure 2).
3.3 Safety and efficacy
Catheter-related and ADE were recorded. In 10 of 260 OPAT episodes (4%) a line-related adverse event occurred whereby ADE occurred in 36 cases (14%) (Table 3). ADE occurred in connection with β-Lactam antibiotics (ertapenem, n=11; piperacillin/tazobactam, n=6; penicillin, n=2; flucloxacillin, n=1; ceftriaxon, n=4; cefepime, n=3; ceftazidim, n=3; cefiderocol, n=1), lipopeptides (daptomycin, n=3), aminoglycosides (gentamicin, n=1) and antifungals (amphotericin B, n=1). There was no association of ADE with length of IV- treatment (p=0.81).
Table 3. Adverse drug-related (ADE) and line-related events. Note: Several ADEs may have occurred in one OPAT episode.
Characteristics
|
OPAT episodes, n=260
|
Drug related AEs (ADEs) n (%)
|
36 (14)
|
Diarrhea
|
10
|
GIT complaints
|
9
|
Allergy
|
5
|
Fatigue
|
2
|
Vertigo
|
2
|
Hepatitis
|
2
|
Thrombocytopenia
|
2
|
Eosinophilia
|
2
|
Leukocytosis
|
1
|
Clostridia difficile infection
|
1
|
Drug fever
|
1
|
Taste change
|
1
|
Vaginal candidiasis
|
1
|
Hepatitis
|
1
|
Line-related events n (%)
|
10 (4)
|
Occlusion
|
5
|
Phlebitis
|
3
|
Dislocation
|
2
|
No drug-related AE or line-related event n (%)
|
214 (82)
|
Abbreviations: Outpatient parenteral antibiotic therapy, OPAT; Gastrointestinal, GIT; adverse event, AE
Readmission of the patient during or up to 30 days after OPAT was necessary for 71 episodes (27%). Thereof, two events were directly related to OPAT (1 ADE and 1 line-related complication). The majority of the readmissions were the result of clinical deterioration because of uncontrolled infection (n=31; 44%), elective rehospitalizations (n=21; 30%) or non-infection-related new events (n=17; 25%). After removal of OPAT episodes with elective rehospitalizations or non-infection related new events there was no association of readmissions with age (p=0.38) or duration of IV treatment (p=0.72). There was a trend of an association with readmission and with CCI (p=0.08) and OPAT setting (p=0.06), suggesting that more readmissions happened in the case of homecare-OPAT and with increasing CCI, respectively.
Clinical cure was achieved in 77% of all recorded OPAT episodes (n=199). In 61 OPAT episodes, no clinical cure was achieved: (1) In 6% (n=15) of OPAT episodes antimicrobial treatment was not completed as anticipated, and/or (2) re-start of antimicrobial treatment was needed in 48 cases and/or (3) a positive culture with the primary pathogen occurred in 30 OPAT episodes, respectively. The OR for clinical cure was negatively associated with CCI per 1 unit higher (OR 0.85 (95% CI 0.78-0.93) and there was a trend of a negative association for age per 10 years older (OR 0.84 (95% CI 0.70-1.0) (Table 5).
Table 4: Cure analyses of 260 OPAT episodes. OR calculations are based on age per 1 years older and CCI per 1 unit higher.
|
Total
n=260 (100%)
|
Clinical cure
n=199 (77%)
|
No clinical cure
n=61 (23%)
|
OR
(95% CI)
|
P
|
Age,
median years IQR
|
57
(45-68)
|
56
(44-68)
|
60
(48-71)
|
0.84
(0.70-1.0)
|
0.103
|
Charlson Comorbidity Index CCI,
median IQR
|
3
(1-5.5)
|
3
(1-5)
|
4
(2-7)
|
0.85
(0.78-0.93)
|
0.001
|
Abbreviations: Confidence Interval, CI; Odds ratio, OR; Outpatient parenteral antibiotic therapy, OPAT; interquartile range (IQR); intravenous, IV
There were no associations with female sex (OR 1.4 (95% CI 0.75-2.6), body mass index (BMI < 19 kg/m2: OR 2.4 (95% CI 0.27-21), BMI 18-25 kg/m2; reference; BMI 25-35 kg/m2: OR 1.2 (95% CI 0.64-2.3); BMI > 35 kg/m2: OR 0.62 (95% CI 0.18-2.1)), OPAT setting (homecare OPAT: OR 0.96 (95% CI 0.49-1.9); self-administered OPAT: OR 1.4 (95% CI 0.75-2.6); reference hospital OPAT)), venous access (peripheral catheter OR 0.76 (95% CI 0.39-1.5; reference PICC line)), and urinary tract infections (OR 0.69 (95% CI 0.36-1.3; reference all other infection types)).
3.4 Bed days saved
The OPAT service was constantly increasing over the years delivering overall 3934 days of treatment (Figure 3).
Assuming hypothetically that a free bed saves 2500 CHF per day, the saving costs of OPAT would have amounted to 9’835’000 CHF over 47 months. The single longest patient episode was a patient receiving meropenem followed by ceftriaxone for cerebral actinomycosis (120 days; saving costs of 300’000 CHF).