The prevalence of drug-resistant microorganisms is growing worldwide1,2. In our hospital, extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli (E. coli) causes 70% of pyelonephritis.

Ertapenem is an exceptional antibiotic because of its once-daily dosing and broad spectrum of activity, suitable for outpatient parenteral antimicrobial therapy (OPAT)3. So far there are no reports on the efficacy of OPAT in Mexico. Our objective is to describe the outcomes, safety and cost of outpatient ertapenem therapy (OET) at our hospital.

Outpatient Ertapenem Therapy

Efficacy, Safety and Cost in a high prevalence ESBL-producing Enterobacteriaceae setting Arturo Ortiz-Álvarez, MD; Mónica A. Delgado-Ramírez, MD; Liudmilla Villegas-Acosta, MD; Montserrat Cuevas-Zúñiga, MD; Teresa Hernández-Carrera, NP; Rafael Valdez-Vázquez, MD; Ana Patricia Rodríguez-Zulueta, MD.

Hospital General Dr. Manuel Gea González , Mexico City, Mexico.

Study Design

We report a case series from the OPAT clinic at our Institution. The primary outcomes were cure, relapse and recurrence of infection. Side effects and complications of IV ertapenem therapy were also registered.

Patient Population

We included adult patients that received OET from January 28th 2014 to 28th December 2014 for a confirmed infections caused by ESBL-producing bacteria or as empiric treatment. Inpatients receiving ertapenem that were later discharged to the OPAT clinic were included.

In order to perform the cost analysis we randomly selected 20 patients with a diagnosis of pyelonephritis that received OET after hospital discharge (OET group) and compared them to patients who received entirely inpatient ertapenem therapy (IET); for this we allocated the first 20 cases of pyelonephritis in hospital discharges during 2013.

Definitions

Cure was defined as resolution of signs and symptoms of infection and improvement of laboratory and imaging studies at the end of OET. Episodes were classified as relapse if symptoms returned <30 days after termination of OET or recurrent if the interval was >30 days. Diagnosis, treatment duration, ertapenem side effects and venous line complications were established by the attending ID specialist.

In our hospital, OET is cost-effective and safe when compared to inpatient therapy.

Introduction

Patients and methods

Table 1. Baseline characteristics of the 99 patients

with OET n (% or SD)

Female 61 (62)

Mean age (years) 48±17

Diabetes mellitus

Arterial hypertension

Liver disease

Human immunodeficiency virus infection

Immunosuppressive therapy

Glomerular filtration rate <60ml/min

Obesity

Surgery in the preceding 3 months

Hospitalization in the 3 preceding months

39 (39)

19 (19)

5 (5)

2 (2)

3 (3)

3 (3)

17 (17)

25 (25)

45 (45)

Received 1 or 2 antibiotics in the preceding 3 months

Received >3 antibiotics in the preceding 3 months

41 (80)

10 (20)

Characteristics of the 88 patients

that required hospitalization

n (% or SD)

Received other IV antimicrobial prior to ertapenem 54 (61)

Days since admission to the beginning of ertapenem

Urinary tract infection (UTI) 1 a 3 days

Abdominal abscess > 4 days

4.4±6

44 (88)

14 (67)

Results

Conclusion Type of

infection

No. of

patients

No. of days

IET + OET

(mean±SD)

No. days

OET

(mean±SD)

Cure

(%)

No. patients

readmitted

after OET

No. patients

with relapse

or recurrence

No. patients

with

phlebitis

UTI 55 14 ± 9 7 ± 6 96 2 2 1

Abdominal

abscess 21 15 ± 10 8 ± 6 100 0 0 0

SSTI 9 13 ± 9 6 ± 5 89 0 1 0

JBI 7 42 ± 10 25 ± 6 100 1 0 1

GTI 4 13 ± 8 10 ± 6 100 0 0 0

Catheter-

related

bacteremia

3 14 ±8

10 ± 5

100 0 0 0

Total 99 15 ±9 9 (±6) 97 3 3 2

Table 4. Comparison of total cost of treatment in

patients with pyelonephritis in USD

Socio economic level OET IET*

1 $ 323 (n=7) $ 1, 221 (n=9)

2 $ 581 (n=13) $ 1, 539 (n=10)

Table 2. Microbiological data

Samples n Microorganism n (%)

Urine

culture *

49 ESBL-producing E. coli

None

29 (59)

20 (41)

Blood

culture ¬

55 ESBL-producing E. coli¶

ESBL-producing Salmonella

None

19 (34)

1 (2)

35 (64)

Abdominal-

abscess

18 ESBL-producing E. coli

C. freundii

None

14 (78)

1 (5)

3 (17)

Table 3. Clinical outcomes of patients with OET

Throughout the study period 137 patients initiated OPAT and 99 of them received OET. Baseline characteristics are described in Table 1 and microbiological data in Table 2.

*Patients with urinary tract infection (pyelonephritis, renal abscess and cystitis), ¬ Total population, ¶ 2 SSTI, 2 catheter-related bacteremias and 15 UTI

SSTI: skin and soft tissue infection, JBI: Joint and bone infection, GTI: genital tract infection, OET: Outpatient ertapenem therapy

Ertapenem therapy

Eighty eight patients required admission and received OET after discharge while 11 received ertapenem entirely as outpatients. Ninety-four percent of the patients received OET through a peripheral catheter. The duration of ertapenem therapy is described in Table 3.

We had one case of non-Clostridium difficile diarrhea, classified as adverse event. Intravascular line complications during OET included phlebitis in two patients.

Cost analysis The introduction of OPAT prevented 863 hospitalization days in the 99 patients with OET. The average cost of pyelonephritis treatment was significantly lower with OET ($928.00 USD cheaper per patient) compared to IET, as seen in Table 4. Costs per patient were significantly greater in patients receiving IET compared to OET.

1. Seaton RA, Barr DA. European Journal of Internal Medicine Outpatient parenteral antibiotic therapy : Principles and practice. Eur J Intern Med. 2013;24(7):617–623. doi:10.1016/j.ejim.2013.03.014.

2. Gales AC, Castanheira M, Jones RN, Sader HS. Antimicrobial resistance among Gram-negative bacilli isolated from Latin America: results from SENTRY Antimicrobial Surveillance Program (Latin America, 2008-2010). Diagn Microbiol Infect Dis 2012;73:354-60.

3. Chapman ALN, Dixon S, Andrews D, Lillie PJ, Bazaz R, Patchett JD. Clinical efficacy and cost-effectiveness of outpatient parenteral antibiotic therapy (OPAT): A UK perspective. J Antimicrob Chemother. 2009;64(September):1316–1324. doi:10.1093/jac/dkp343.

References

Urinary tract infection

Abdominal abscess

Skin and soft tissue infection

Bone and joint infection

Genital tract infection

Catheter related bacteremia

Figure 1. Type of infection

Outcomes

Overall cure rate was 97% (see Table 3). We detected one relapse (renal abscess 12 days after the end of OET) and two cases of recurrent infection (one skin and soft tissue infection and one episode of pyelonephritis at days 35 and 34 respectively). Three patients were readmitted after OET (one episode of phlebitis, one recurrence and one relapse).

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OET: outpatient ertapanem therapy; IET: inpatient ertapenem therapy * One patient in the control group belonged to socioeconomic level 3

Contact +52 4000- 3000 ext. 3288 ortizalvarez_arturo@hotmail.com