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Recommendations for outpatient parenteral antimicrobial therapy in Brazil.

Introduction

The use of outpatient parenteral antimicrobial therapy (OPAT) as a treatment strategy with the aim of de-hospitalizing patients has been growing since its advent during the 1970s. (1) OPAT has become a safe and standardized practice for patients presenting with various infections who require long-term parenteral antimicrobial therapy. International consensus guidelines have determined that OPAT can be performed in physicians' offices, clinics, specialized infusion centers or in patients' homes. (2,3)

Patients should be selected for this type of treatment by physicians who are familiar with the infectious conditions that will be treated. They should also be evaluated by nurses who have experience in implementing and managing long-term venous access, and by social workers who will decide whether patients present social, economic and cultural conditions that allow them to be safely treated this way. If patient evaluation and selection are performed adequately, OPAT is acknowledged to be safe, effective, practical and cost-effective.

Its impacts from economic and hospital bed-occupancy points of view are high, as are the undeniable benefits to patients' (and their families') quality of life. By decreasing patients' need for and length of hospitalization, OPAT has also shown an impact through reducing healthcare-related infection rates. (4-7)

Organization of OPAT programs

The organization of OPAT programs should be hierarchical, such that patients are evaluated at an OPAT reference center before being sent to a healthcare unit where they will be treated with either a day-hospital regimen or through home-care. Likewise, every service that receives patients for OPAT needs to rely on a reference center to which patients can be promptly referred in the event of adverse events related to the treatment, along with the transportation logistics for such referrals. In addition to this referral and counter-referral organization, the structure of OPAT programs should always envisage the following:

* Multidisciplinary team trained to make evaluations regarding patients' eligibility for OPAT and to conduct follow-up on this type of therapy. These team should be led by a physician, preferably an infectious disease specialist with experience in using long-term parenteral antimicrobials. In addition, each team needs to include a nurse with experience in manipulating central venous access, and a social worker. A clinical pharmacist may also be included in the team, although this is still an uncommon professional in most Brazilian healthcare services. The functions of each of these professionals are described in Table 1. Other professionals can also be included in the team, according to the patient's profile and availability of the OPAT service provider. (1)

* Up-to-date protocols for the rational use of antimicrobials and manipulation of venous access.

* Continuing educational programs to train the professionals involved in patient care within OPAT.

Patient evaluation and eligibility criteria for OPAT

Clinical /actors

The main patient eligibility criterion for OPAT programs is the need for long-term parenteral antimicrobial treatment, preferably based on culture and antibiogram results. Oral treatment should always be given preference in cases whenever possible. In addition, only patients who are clinically stable and whose infection and possible comorbidities are under control can be referred for OPAT.

Sociocultural and family-related factors

Patients referred for OPAT should have the social and/or familial support needed for the particular features of this therapy. They need to assume co-responsibility for the treatment, especially in relation to adherence to the therapy and maintenance of venous access. In cases in which drug infusion can be performed at the patient's home, team members should also certify that the location demonstrates the necessary conditions for safely performing venous infusions.

Patient's and caregiver's inability to comprehend the OPAT program, including catheter care and locomotion difficulties, should be considered an exclusion criterion for OPAT. It is not recommended that patients with histories of active alcoholism or drug addiction be candidates for this therapy practice, especially because of the risk of improper catheter manipulation. Table 2 shows the main characteristics to be evaluated for patient eligibility for OPAT.

Diagnosis of eligibility for OPAT

Patients with diagnoses of the infections described below are considered eligible for treatment under an OPAT regimen:

* Complicated upper respiratory tract infections, including malignant external otitis, necrotizing external otitis and rhinosinusitis (8-11);

* Respiratory infections, including complicated pneumonias, empyemas, lung abscesses, cystic fibrosis, exacerbations of the conditions of chronic obstructive pulmonary disease (COPD), infected bronchiectasis, community-acquired pneumonia, and nosocomial pneumonia (12);

* Microbiologically-proven endocarditis due to Streptococcus viridians (13,14) in patients who do not present signs of possible complications of infectious endocarditis or predictors of poor prognosis. Patients with conditions related to other agents or without microbiological proof are not considered eligible for OPAT in Brazil;

* Complicated infections of the urinary tract (15,16);

* Intra-abdominal infections, including secondary peritonitis, abscess, sepsis, cholecystitis with perforation or abscess, intra-abdominal abscess, appendicitis with perforation or abscess, stomach or intestinal perforation, peritonitis, diverticulitis with perforation, peritonitis or abscess. (17,18) Patients are considered eligible for OPAT when they have stabilized and do not require new surgical interventions;

* Skin and soft-tissue infections, including cellulitis, large abscesses, surgical wound infections, infected burns, infected ulcers, infected bites and pyomyositis. (19,20) Patients are considered eligible for OPAT when they have stabilized and do not require surgical interventions;

* Osteoarticular infections, including pyoarthritis, acute and chronic osteomyelitis, and orthopedic implant-related infections. (5,21)

Venous access and antimicrobial infusion devices

The type of medication, duration of therapy, frequency of antimicrobial administration, and condition of the patient's venous network should be taken into account when determining venous access mechanisms allowed for OPAT, either using peripheral or central devices. Central catheters are indicated in cases of parenteral antimicrobial treatment with an estimated duration longer than 14 days and when the prescribed antibiotics have a pH lower than five or higher than nine.

Valved catheters of the PICC type (peripherally inserted central catheter) should be the device of choice for performing OPAT. Semi-implantable or totally-implantable catheters can be used, especially if the patient is already using one of these devices. Use of short-term central venous catheters (double or mono-lumen) for OPAT is contra-indicated.

Use of peripheral venous access for OPAT is possible, but it requires certainty that the patient has a good-quality peripheral venous network. (22) Table 3 shows the types of central catheters indicated for OPAT in Brazil and their indications, duration, advantages and disadvantages.

Depending on the patient's clinical conditions and comorbidities, larger or smaller dilution volumes may be required. In these cases, participation of a physician, nurse, and clinical pharmacist is important for prescribing and guiding drug dilution. Table 4 shows the general recommendations for reconstitution, dilution and infusion of antimicrobials used in OPAT, along with doses and posology of each drug envisaged. These recommendations can be modified according to the patient's clinical condition. Administration of antimicrobials in bolus form is not recommended. (2) Antimicrobial infusion should preferentially be performed under supervision of a nurse with experience in manipulating central catheters, in accordance with the following recommendations (5):

* Prepare all materials to be used for antimicrobial infusion in advance;

* Sanitize hands before and after manipulating the catheter. Procedure gloves must be used;

* Before antimicrobial infusion, a flush using 0.9% saline solution should always be performed using 10 mL syringes (never use syringes with smaller or larger volumes, because of the pressure difference and risk of catheter rupture). In the case of patients with semi-implanted catheters (Hickman, Broviac or Leonard type) or totally implanted catheters (port-a-cath), 5 mL of blood should be aspirated before flushing, to remove the previously infused heparin solution;

* During preparation for antimicrobial infusion, the recommendations for reconstitution, dilution and duration of administration of the antibiotics should be carefully followed;

* At the end of the infusion, a new flush of 0.9% saline solution should be performed using a 10 mL syringe;

* For patients with semi-implanted catheters (Hickman, Broviac or Leonard type) or totally implanted catheters (port-a-cath), a seal should also be placed using 3-5 mL of heparin solution (100 IU/mL) after the last flush of saline solution. The catheter manufacturer's recommendations should be reviewed;

* The dressing and catheter stabilizer (if present) should be changed every seven days. Use transparent film to observe the insertion site;

* Communication between patients and their referral nurses is important in cases of possible accidents, such as catheter perforation, obstruction and exudation in the insertion area, or signs of bacteremia, phlebitis or thrombosis;

* Do not use the catheter if there are signs of infection during its insertion (hyperemia or exudation in the skin around the catheter) or bacteremia. Immediately send the patient to the team that performed the insertion or that has been designated for dealing with adverse event occurrences;

* In the event of obstruction, do not attempt to clear the catheter; in such cases, a peripheral venous puncture should be performed and the team that performed the insertion or that has been designated for dealing with adverse event occurrences should be contacted in order to schedule a new catheter insertion;

* If the PICC has a caliber smaller than 3.8 Fr, blood must not be collected and blood byproducts must not be transfused.

Protocols for antimicrobial use and monitoring

Antimicrobial use within an OPAT regimen

Referral of patients for OPAT requires use of antimicrobial protocols adapted to this reality, especially regarding drug posology: the drugs need to be administered once or twice a day. The choice of antimicrobials should be based on culture and antibiogram results, if possible, and patient's comorbidities and possible drug interactions should be considered. (5,2,23-26)

In Brazil, the following antimicrobials are considered acceptable for use in OPAT: amikacin, gentamicin, ceftriaxone, cefepime, ceftazidime, ceftaroline, ertapenem, linezolid (when formulation for oral use is not available), tigecycline, daptomycin, teicoplanin, vancomycin, amphotericin B (lipid formulations), caspofungin, anidulafungin, micafungin and voriconazole (when formulation for oral use is not available). Meropenem was also included, considering this drug could safely be administered twice a day in patients with stable clinical condition. (5,27) Table 4 shows the dose and posology recommendations for using antimicrobials in OPAT in Brazil for patients with normal renal function, as well as recommendations for reconstitution, dilution and infusion of these drugs. Table 5 shows dose and posology recommendations for children outside of the neonatal period. In these cases, care regarding reconstitution, dilution and duration of infusion need to be specified in accordance with the instructions from the physician responsible for the case.

Monitoring

Patients undergoing OPAT should be monitored from the clinical and laboratory points of view. Adverse events include catheter-related issues (insertion site infection, bacteremia, blood stream infection and air embolism), drug infusion-related problems, and side effects relating to the antimicrobial used. The entire multidisciplinary team needs to be alert to the occurrences of these events and be trained to take the necessary actions. The team should also be trained to detect possible hypersensitivity reactions (allergies) to antimicrobials, which may appear at any time during the treatment.

Laboratory drug monitoring should be conducted every two weeks for the majority of the drugs used. Because of the higher reported occurrence of renal side effects, patients using amikacin, gentamicin, vancomycin and amphotericin B (lipid formulations) should have weekly doses of urea and creatinine. (5,2) When necessary, monitoring of serum levels of vancomycin can also be performed weekly. (2) Table 6 shows the monitoring recommendations for patients undergoing OPAT according to the antimicrobial used. These recommendations can be adapted according to the presence of comorbidities or particular situations of each patient.

Cost-effectiveness

Implementation of an OPAT system has been shown to impact the number and duration of hospitalizations of patients with infections that require long-tern parenteral treatments. It also ensures favorable clinical outcomes and improves the patient's quality of life. In addition to individual benefits, OPAT enables better allocation of hospital beds and resources if implemented as a healthcare policy because it demonstrates high cost-effectiveness.

Studies conducted in other countries have shown that the cost of a patient treated with an OPAT regimen is between 40 and 75% lower than the cost of a patient who is treated with a hospital regimen. This resource saving can reach 40,000 dollars per patient. (28-32) In Brazil, implementation of an OPAT program in a public orthopedics and trauma hospital was shown to enable reallocation of over 11,000 hospital beds for patients who required hospitalization. (5)

Therefore, it can be concluded that, in addition to the advantages mentioned above, implementation of OPAT strategies in Brazil can lead to better allocation of healthcare resources, both within the public National Health System and in the private (supplementary) system.

Conflicts of interest

- Priscila R. Oliveira: Declares participation in educational activities for MSD, Sanofi-Aventis, Bayer Schering Pharma, Pfizer and Abbott and has developed clinical research activities for MSD and Pfizer.

- Vladimir C. Carvalho: Declares participation in educational activities for MSD and Pfizer and has developed clinical research activities for MSD and Pfizer.

- Sergio Cimmerman: Declares participation in educational activities for Abbvie, BMS, Farmoquimica, Gilead, Janseen, MSD, United Medical.

- Ana Lucia M. Lima: Member of advisory board for Sanofi-Aventis. Declares participation in educational activities for MSD, Sanofi-Aventis, Bayer Schering Pharma, Pfizer and Abbott and has developed clinical research activities for MSD and Pfizer.

Acknowledgments

This document was produced under the responsibility of the Brazilian Society of Infectious Diseases. The organization of the meeting that enabled its preparation was supported by AstraZeneca, Bayer Schering Pharma, MSD, Pfizer and Sanofi. The sponsors did not interfere in the elaboration or content of these recommendations.

Appendix A.

Diretrizes Brasileiras para Terapia Antimicrobiana Parenteral Ambulatorial group: Ana Cristina Gales, Universidade Federal de Sao Paulo; Bil Randerson Bassetti, Escola Superior de Ciencias da Santa Casa de Misericordia de Vitoria; Carla Sakuma de Oliveira, Universidade Estadual do Oeste do Parana; Cassia da Silva Felix, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo; Cesar Leite, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo; Eitan Naaman Berezin, Faculdade de Ciencias Medicas da Santa Casa de Sao Paulo; Eliana Lima Bicudo dos Santos, Secretarla da Saude do Distrito Federal; Guillermo S. Pinheiro de Lemos, Hospital de Urgencias de Goiania; Ivan Silva Marinho, Hospital e Maternidade Sao Camilo; Mariangela Ribeiro Resende, Universidade Estadual de Campinas; Marcos Cyrillo, Secretarla Municipal de Saude de Sao Paulo; Mario Sergio Lei Munhoz, Universidade Federal de Sao Paulo; Sylvia Maria de Lemos Hinrichsen, Universidade Federal de Pernambuco; Tania Mara Varejao Strabelli, Universidade de Sao Paulo.

REFERENCES

(1.) Paladino JA, Poretz D. Outpatient parenteral antimicrobial therapy today. Clin Infect Dis. 2010;51 Suppl. 2:S198-208.

(2.) Tice AD, Rehm SJ, Dalovisio JR, et al. Practice guidelines for outpatient parenteral antimicrobial therapy. IDSA guidelines. Clin Infect Dis. 2004;38:1651-72.

(3.) Chapman AL. Outpatient parenteral antimicrobial therapy. BMJ. 2013;346:fl585.

(4.) MacKenzie M, Rae N, Nathwani D. Outcomes from global adult outpatient parenteral antimicrobial therapy programmes: a review of the last decade. Int J Antimicrob Agents. 2014;43:7-16.

(5.) Oliveira PR, Felix C da S, Carvalho VC, et al. Outpatient parenteral antimicrobial therapy for orthopedic infections--a successful public healthcare experience in Brazil. Braz J Infect Dis. 2016;20:272-5.

(6.) Fisher DA, Kurup A, Lye D, et al. Outpatient parenteral antibiotic therapy in Singapore. Int J Antimicrob Agents. 2006;28:545-50.

(7.) Patel S, Abrahamson E, Goldring S, Green H, Wickens H, Laundy M. Good practice recommendations for paediatric outpatient parenteral antibiotic therapy (p-OPAT) in the UK: a consensus statement. J Antimicrob Chemother. 2015;70:360-73.

(8.) Chen CN, Chen YS, Yeh TH, Hsu CJ, Tseng FY. Outcomes of malignant external otitis: survival vs mortality. Acta Otolaryngol. 2010;130:89-94.

(9.) Soudry E, Hamzany Y, Preis M, Joshua B, Hadar T, Nageris BI. Malignant external otitis: analysis of severe cases. Otolaryngol Head Neck Surg. 2011;144:758-62.

(10.) McCoul ED, Tabaee A. A practical approach to refractory chronic rhinosinusitis. Otolaryngol Clin North Am. 2017;50:183-98.

(11.) Handzel O, Halperin D. Necrotizing (malignant) external otitis. Am Fam Physician. 2003;68:309-12.

(12.) Candel FJ, Julian-Jimenez A, Gonzalez-Del Castillo J. Current status in outpatient parenteral antimicrobial therapy: a practical view. Rev Esp Quimioter. 2016;29:55-68.

(13.) Bashore TM, Cabell C, Fowler V Jr. Update on infective endocarditis. Curr Probi Cardiol. 2006;31:274-352.

(14.) Habib G, Lancellotti P, Antunes MJ, et al. [2015 ESC Guidelines for the management of infective endocarditis. The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC)]. G Ital Cardiol (Rome). 2016;17:277-319.

(15.) Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011;52:el03-20.

(16.) Shakil J, Piracha N, Prasad N, et al. Use of outpatient parenteral antimicrobial therapy for transrectal ultrasound-guided prostate biopsy prophylaxis in the setting of community-associated multidrug-resistant Escherichia coli rectal colonization. Urology. 2014;83:710-3.

(17.) Sartelli M, Viale P, Koike K, et al. WSES consensus conference: guidelines for first-line management of intra-abdominal infections. World J Emerg Surg. 2011;6:2.

(18.) Sawyer RG, Claridge JA, Nathens AB, et al. Trial of short-course antimicrobial therapy for intraabdominal infection. N Engl J Med. 2015;372:1996-2005.

(19.) Seetoh T, Lye DC, Cook AR, et al. An outcomes analysis of outpatient parenteral antibiotic therapy (OPAT) in a large Asian cohort. Int J Antimicrob Agents. 2013;41:569-73.

(20.) Talan DA, Salhi BA, Moran GJ, et al. Factors associated with decision to hospitalize emergency department patients with skin and soft tissue infection. West J Emerg Med. 2015;16:89-97.

(21.) Marculescu CE, Berbari EF, Cantey JR, Osmon DR. Practical considerations in the use of outpatient antimicrobial therapy for musculoskeletal infections. Mayo Clin Proc. 2012;87:98-105.

(22.) Infusion Nurses Society (INS). Infusion therapy standards of practice. Infusion Nurses Society > Home; 2016. Available in: https://www.ins1.org

(23.) Chapman AL, Seaton RA, Cooper MA, et al. Good practice recommendations for outpatient parenteral antimicrobial therapy (OPAT) in adults in the UK: a consensus statement. J Antimicrob Chemother. 2012;67:1053-62.

(24.) Seaton RA, Barr DA. Outpatient parenteral antibiotic therapy: principles and practice. Eur J Intern Med. 2013;24:617-23.

(25.) Gilchrist M, Seaton RA. Outpatient parenteral antimicrobial therapy and antimicrobial stewardship: challenges and checklists. J Antimicrob Chemother. 2015;70:965-70.

(26.) Shah PJ, Bergman SJ, Graham DR, Glenn S. Monitoring of outpatient parenteral antimicrobial therapy and implementation of clinical pharmacy services at a Community Hospital Infusion Unit. J Pharm Pract. 2015;28:462-8.

(27.) Bowker KE, Holt HA, Lewis RJ, Reeves DS, MacGowan AR Comparative pharmacodynamics of meropenem using an in-vitro model to simulate once, twice and three times daily dosing in humans. J Antimicrob Chemother. 1998;42:461-7.

(28.) Chapman AL, 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;64:1316-24.

(29.) Pena A, Zambrano A, Alvarado M, Cerda J, Vergara R. Evaluation of the effectiveness, safety and costs of outpatient intravenous antimicrobial treatment (OPAT) vs hospitalized in urinary infection in pediatrics. Rev Chil Infectol. 2013;30:426-34.

(30.) Lacroix A, Revest M, Patrat-Delon S, et al. Outpatient parenteral antimicrobial therapy for infective endocarditis: a cost-effective strategy. Med Mal Infect. 2014;44:327-30.

(31.) Bernard L, El-Hajj, Pron B, et al. Outpatient parenteral antimicrobial therapy (OPAT) for the treatment of osteomyelitis: evaluation of efficacy, tolerance and cost. J Clin Pharm Ther. 2001;26:445-51.

(32.) Psaltikidis EM, Silva E, Bustorff-Silva JM, Moretti ML, Resende MR. Economic analysis of outpatient parenteral antimicrobial therapy (Opat): a systematic review. Value Health. 2015;18:A582-3.

Priscila R. Oliveira (a,*), Vladimir C. Carvalho (a), Sergio Cimerman (b,c), Ana Lucia Munhoz Lima (a), on behalf of the Diretrizes Brasileiras para Terapia Antimicrobiana Parenteral Ambulatorial group*

(a) Universidade de Sao Paulo, Sao Paulo, SP, Brazil

(b) Universidade de Mogi das Cruzes, Mogi das Cruzes, SP, Brazil

(c) Institute de Infectologia Emilio Ribas, Sao Paulo, SP, Brazil

(*) Corresponding author.

E-mail address: priscila.rosalba@hc.fm.usp.br (P.R. Oliveira).

(*) See Appendix A for members of Diretrizes Brasileiras para Terapia Antimicrobiana Parenteral Ambulatorial group.

http://dx.doi.Org/10.1016/j.bjid.2017.06.006

ARTICLE INFO

Artide history:

Received 22 May 2017

Accepted 20 June 2017

Available online 14 July 2017
Table 1--Professionals required for an OPAT program and their
attributes.

Professional             Main attributes within the team

Physician (preferably    - Team leadership;
an infectious
disease specialist)      - Clinical evaluation of patient's infectious
                         conditions and their comorbidities;
                         - Determination of whether clinical
                         stability allowing OPAT exists;
                         - Prescription of the antimicrobial to
                         be used;
                         - Participation in the decision of what
                         type of catheter should be used by patients;
                         - Participation in assessments on patient's
                         and caregiver's capacity for comprehension;
                         - Initial evaluation on patients who are
                         recommended for OPAT (a);
                         - Clinical and laboratory monitoring of
                         patients undergoing OPAT (a);
                         - Clinical evaluation of possible events
                         presented during treatment and decision
                         on the need for transferring to the reference
                         center for OPAT (a).
Nurse (with experience   - Prescription of drug infusion procedures
in manipulation          for OPAT (a) (reconstitution and dilution of
of central catheters)    antimicrobials and duration of infusion)
                         in accordance with the protocol;
                         - Participation in the decision
                         regarding what type of catheter should
                         be used by patients;
                         - Participation in assessments of patient's
                         and caregiver's capacity for comprehension;
                         - Supervision of antimicrobial infusion;
                         - Daily inspection of the catheter insertion
                         site and communication with the doctor in
                         the event of abnormalities;
                         - Minimum of once-weekly changing of
                         dressings at catheter insertion site;
                         - Patient guidance regarding catheter care;
                         - Patient guidance regarding drug storage
                         precautions;
                         - Evaluation of patient's home sanitary
                         conditions, in the event of referral for
                         homecare OPAT (a).
Social worker            - Participation in assessments of patient's
                         and caregiver's capacity for comprehension;
                         - Documentation of patient's and their
                         caregiver's consent to OPAT;
                         - Evaluation of patient's social conditions
                         for OPAT (especially transportation);
                         - Establishment of contact between
                         patient's hospitalization service or
                         reference center for OPAT and the
                         healthcare service where the therapy
                         will take place.
Clinical pharmacist      - Participation in assessments of
                         patient's and caregiver's capacity for
                         comprehension;
                         - Participation in prescription of drug
                         infusion procedures for OPAT
                         (antimicrobial reconstitution
                         and dilution, and duration of
                         infusion), in accordance with
                         the protocol;
                         - Patient guidance about drug storage
                         precautions;
                         - Participation in clinical and
                         laboratory monitoring of patients
                         undergoing OPAT.

OPAT, outpatient parenteral antimicrobial therapy.

Table 2--Main characteristics for patient eligibility for OPAT.

Clinical factors         * Need for long-term parenteral antimicrobial
                         treatment;
                         * Clinical stability;
                         * No histories of active alcoholism or drug
                         addiction.
Sociocultural and        * Comprehension of OPAT and ability to
                         collaborate;
family-related factors   * Ability to transport the patient to the
                         infusion center, in cases of treatment under
                         a day hospital regimen;
                         * Sanitary conditions of drug infusion at
                         home, in cases of homecare.

OPAT, outpatient parenteral antimicrobial therapy.

Table 3--Types of central lines indicated for OPAT in Brazil.

Type of central line       Indication               Duration

Valved peripherally        Antimicrobial treatment  Up to 6 months
inserted central catheter  with estimated duration
(valved PICC)              longer than 14 days

Tunneled semi-implanted    Antimicrobial treatment  Up to 6 months
central catheter           with estimated duration
                           longer than 14 days

Totally implanted central  Antimicrobial treatment  Up to 5 years
catheter                   with estimated duration
                           longer than 14 days

Type of central line       Characteristics

Valved peripherally        - Cost-effective
inserted central catheter  - Easy insertion
(valved PICC)              - Lower incidence of infection
                           - Lower risk of air embolism and reflux
                           - Higher safety for homecare therapy
Tunneled semi-implanted    - Surgical implantation
central catheter           - Open extremity
                           - Blockage using heparin solution is needed
                           - Low risk of infection
                           - 2nd choice for treatment, when insertion
                           of PICC is not possible
Totally implanted central  - High cost
catheter                   - Surgical implantation
                           - Blockage using heparin solution is needed
                           - Access through Huber needle, replaced
                           every seven days
                           - High risk of infection with daily
                           manipulation (generally indicated for
                           chemotherapy against cancer, which requires
                           less manipulation)
                           - Indication only for OPAT should be avoided

OPAT, outpatient parenteral antimicrobial therapy.

Table 4--Recommendations and instructions for antimicrobial use in OPAT
in Brazil.

Antimicrobial    Dose and posology      Reconstitution
                 for normal renal and
                 hepatic functions

Amikacin         15 mg/kg once a day    Not required

Gentamicin       5 mg/kg once a day     Not required
Cefepime         2 g twice a day        10 mL of sterile distilled
                                        water
Ceftaroline      600 mg twice a day     20 mL of sterile distilled
                                        water
Ceftazidime      2 g twice a day        5-10 mL of sterile distilled
                                        water
Ceftriaxone      2 g once a day         10 mL of sterile distilled
                                        water
Ertapenem        1 g once a day         10 mL of sterile distilled
                                        water
Meropenem        2 g twice a day        20 mL of sterile distilled
                                        water
Vancomycin       15 mg/kg twice a day   10 mL of sterile distilled
                                        water
Teicoplanin      6 mg/kg once a day     10 mL of sterile distilled
                                        water
Daptomycin       4-6 mg/kg once a day   10 mL of 0.9%SS
Linezolid        600 mg twice a day     Not required

Tigecycline      50 mg twice a day      Not required
Anidulafungin    100 mg once a day      30 mL of its own diluent
Caspofungin      50 mg once a day       10 mL of sterile distilled
                                        water
Micafungin       100 mg once a day      5 mL of 0.9% SS
Voriconazole     3-4 mg/kg twice a day  19 mL of sterile distilled
                                        water
Amphotericin B   5 mg/kg once a day     20 mL of sterile distilled
(lipid complex)                         water
Amphotericin B   3-5 mg/kg once a day   10 mL of sterile distilled
(liposomal)                             water

Antimicrobial    Dilution                         Duration of
                                                  infusion

Amikacin         100-200 mL of 0.9% SS, 5% GS or  30-60 min
                 Ringer's lactate solution
Gentamicin       50-200 mL of 5% GS               30-120 min
Cefepime         50-100 mL of 0.9% SS, 5% GS or   30 min
                 Ringer's lactate solution
Ceftaroline      50-250 mL of 0.9% SS, 5% GS or   30 min
                 Ringer's lactate solution
Ceftazidime      50-100 mL of 0.9% SS, 5% GS or   30-60 min
                 Ringer's lactate solution
Ceftriaxone      50-100 mL of 0.9% SS, 5% GS or   15-30 min
                 Ringer's lactate solution
Ertapenem        50 mL of 0.9% SS                 30 min

Meropenem        250 mL of 0.9% SS or 5% GS       60 min

Vancomycin       200 mL of 0.9% SS or 5% GS       60 min
                 50-100 mL of 0.9% SS, 5% GS or
Teicoplanin      Ringer's lactate solution        60 min
                 50 mL of 0.9% SS
Daptomycin       50-100 mL of 0.9% SS, 5% GS or   30 min
Linezolid        Ringer's lactate solution        30-120 min
                 50 mL of 5% GS
Tigecycline      100 mL of 0.9% SS or 5% GS       30-60 min
Anidulafungin    100 mL of 0.9% SS                90 min
Caspofungin                                       60 min
                 50 mL of 0.9% SS or 5% GS
Micafungin       200-250 mL of 0.9% SS, 5% GS or  60 min
Voriconazole     Ringer's lactate solution        60-120V
                 200-500 mL of 5% GS
Amphotericin B                                    120 min
(lipid complex)  200-500 mL of 5% GS
Amphotericin B                                    120 min
(liposomal)

0.9% SS, 0.9% saline solution; 5% GS, 5% glucose solution. OPAT,
outpatient parenteral antimicrobial therapy.

Table 5--Recommendations of antimicrobials for pediatric patients in
OPAT in Brazil. (a)

Antimicrobial      Dose and posology for normal
                   renal and hepatic functions

Amikacin           15 mg/kg once a day
Gentamicin          7 mg/kg once a day
Cefepime           50 mg/kg/dose twice a day
Ceftaroline        35-45 mg/kg in 3 doses
                   Maximum dose 1200 mg/day
Ceftazidime        50 mg/kg/dose twice a day
Ceftriaxone        50 mg/kg once a day
                   For meningitis, 50 mg/kg/dose twice a day
Ertapenem          15 mg/kg/dose twice a day
Meropenem          40 mg/kg/dose twice a day
Vancomycin         15 mg/kg/dose twice a day
Teicoplanin         6 mg/kg once a day
Daptomycin         There is no standardization
Linezolid          10 mg/kg/dose twice a day
Tigecycline        There is no standardization
Anidulafungin      There is no standardization
Caspofungin        50 mg/m (2) once a day
Micafungin         There is no standardization
Voriconazole        4 mg/kg/dose twice a day
Amphotericin B      5 mg/kg once a day
(lipid complex)
Amphotericin B      3-5 mg/kg once a day
(liposomal)

OPAT, outpatient parenteral antimicrobial therapy.
(a) For children over 28 days old.

Table 6--Recommendations for routine monitoring in patients undergoing
OPAT.

Antimicrobial
                  Complete blood cell
                  analysis

Amikacin          Every 14 days

Gentamicin        Every 14 days

Cefepime          Every 14 days
Ceftaroline       Every 14 days
Ceftazidime       Every 14 days
Ceftriaxone       Every 14 days
Ertapenem         Every 14 days

Meropenem         Every 14 days

Vancomycin        Every 7 days

Teicoplanin       Every 14 days
Daptomycin        Every 14 days
Linezolid         Every 7 days

Tigecycline       Every 14 days

Anidulafungin     Every 14 days
Caspofungin       Every 14 days
Micafungin        Every 14 days
Voriconazole      Every 14 days
Amphotericin B    Every 7 days
(lipid complex)

Amphotericin B    Every 7 days
(liposomal)

Antimicrobial     Minimum frequency of examinations to be performed
                  Renal evaluation        Hepatic evaluation
                  (urea and creatinine)   (ALT, AST, alkaline
                                          phosphatase and,
                                          gamma GT)

Amikacin          Every 7 days            Every 14 days

Gentamicin        Every 7 days            Every 14 days

Cefepime          Every 14 days           Every 14 days
Ceftaroline       Every 14 days           Every 14 days
Ceftazidime       Every 14 days           Every 14 days
Ceftriaxone       Every 14 days           Every 7 days
Ertapenem         Every 14 days           Every 14 days

Meropenem         Every 14 days           Every 14 days

Vancomycin        Every 7 days            Every 7 days

Teicoplanin       Every 14 days           Every 14 days
Daptomycin        Every 14 days           Every 14 days
Linezolid         Every 14 days           Every 14 days

Tigecycline       Every 14 days           Every 7 days

Anidulafungin     Every 14 days           Every 14 days
Caspofungin       Every 14 days           Every 14 days
Micafungin        Every 14 days           Every 14 days
Voriconazole      Every 14 days           Every 14 days
Amphotericin B    Every 3 days            Every 7 days
(lipid complex)

Amphotericin B    Every 3 days            Every 7 days
(liposomal)

Antimicrobial     Minimum frequency of examinations to be performed
                  Potassium     CPK

Amikacin          Every 7 days  -

Gentamicin        Every 7 days  -

Cefepime          -             -
Ceftaroline       -             -
Ceftazidime       -             -
Ceftriaxone       -             -
Ertapenem         -             -

Meropenem         -             -

Vancomycin        Every 7 days  -

Teicoplanin       -             -
Daptomycin        -             Every 7 days
Linezolid         -             -

Tigecycline       -             -

Anidulafungin     -             -
Caspofungin       -             -
Micafungin        -             -
Voriconazole      -             -
Amphotericin B    Every 3 days  -
(lipid complex)

Amphotericin B    Every 3 days  -
(liposomal)

Antimicrobial     Observations

Amikacin          Ototoxicity may
                  occur: monitor
                  hearing and
                  vestibular functions
Gentamicin        Ototoxicity may
                  occur: monitor
                  hearing and
                  vestibular functions
Cefepime
Ceftaroline
Ceftazidime
Ceftriaxone
Ertapenem         A decrease in the
                  convulsive thresholi
                  may occur
Meropenem         A decrease in the
                  convulsive threshold
                  may occur
Vancomycin        Serum level control
                  (vancomycin) can be
                  performed every 7
                  days
Teicoplanin
Daptomycin
Linezolid         Optical neuropathy
                  may occur: monitor
                  visual acuity
Tigecycline       Nausea may occur
                  even in the absence
                  of hepatic enzyme
                  alterations; consider
                  concomitant
                  administration of
                  antiemetics
Anidulafungin
Caspofungin
Micafungin
Voriconazole
Amphotericin B    Weekly dose of
(lipid complex)   magnesium may be
                  necessary
Amphotericin B    Weekly dose of
(liposomal)       magnesium may be
                  necessary

OPAT, outpatient parenteral antimicrobial therapy; AST, aspartate
aminotransferase; ALT, alanine aminotransferase; Gamma GT, gamma
glutamyl-transferase; CPK, creatine Phosphokinase.
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Title Annotation:Review article
Author:Oliveira, Priscila R.; Carvalho, Vladimir C.; Cimerman, Sergio; Lima, Ana Lucia Munhoz
Publication:The Brazilian Journal of Infectious Diseases
Article Type:Report
Geographic Code:3BRAZ
Date:Nov 1, 2017
Words:5062
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