Subcutaneously Administered Antibiotics: a Introduction National Survey of Current Practice from The

View metadata, citation and similar papers at core.ac.uk brought to you by CORE

provided by Elsevier - Publisher Connector

RESEARCH NOTE INFECTIOUS DISEASES

Subcutaneously administered antibiotics: a Introduction national survey of current practice from the

French Infectious Diseases (SPILF) and Sparse data have been published on the pharmacokinetics, ef- Geriatric Medicine (SFGG) society networks ﬁcacy and tolerance of antibiotics administered subcutaneously (sc) [1]. However, current practice among French physicians seems to defy currently available evidence and guidelines. We E. Forestier1, M. Paccalin2, C. Roubaud-Baudron3, T. Fraisse4, performed a survey among infectious diseases (ID) and geriatric G. Gavazzi5 and J. Gaillat6 practitioners in France to estimate the frequency of sc antibi- 1) Service de Maladies Infectieuses, Centre Hospitalier, Chambéry, 2) Service otic use as well as to explore which antibiotics are administered de Gériatrie, Centre Hospitalier Universitaire, Poitiers, 3) Pole de Gérontologie sc, the clinical circumstances and the adverse effects of sc clinique, Centre Hospitalier Universitaire, Bordeaux, 4) Service de Gériatrie, administration. Centre Hospitalier, Alès, 5) Service de Gériatrie, Centre Hospitalier Universitaire, Grenoble and 6) Service de Maladies Infectieuses, Centre Materials and methods Hospitalier, Annecy, France

An online declaratory survey was conducted by the French ID (SPILF) and geriatric (SFGG) society networks in April 2013. An Abstract electronic questionnaire was mailed to the members of both societies (approximately 600 (50% of clinicians) for the SPILF, and 1200 (80% of clinicians) for the SFGG) regarding their sc A national survey was performed to explore antibiotic prescription antibiotic prescription patterns. Participation was on a volun- by the subcutaneous (sc) route among French infectious diseases tary basis. and geriatric practitioners. Among the participating physicians, 367 (96.1%) declared administering sc antibiotics at some point. Results Ceftriaxone was prescribed sc by all but one, and ertapenem, teicoplanin, aminoglycosides and amoxicillin by 33.2%, 39.2%, 35.1% and 15.3%, respectively. The sc route was resorted to Three hundred eighty-two practitioners ﬁlled in the survey (93 mainly in case of unavailable oral, intravenous or intramuscular ID specialists, practicing in 51 acute medical wards, and 289 routes, especially during palliative care. Pain, skin necrosis and geriatricians working in 112 different institutions). Of these, lack of efﬁcacy were the main adverse effects, reported by 140 (48%) operated in short-stay geriatric units, and the others 70.8%, 12.8% and 19.9% of practitioners, respectively. Further worked in rehabilitation care centers, nursing homes and/or studies are needed to precise the indications, modalities and long-term care facilities. tolerance of sc antibiotic use. Three hundred sixty-seven practitioners (96.1%) declared Clinical Microbiology and Infection © 2014 European Society of administering antibiotics sc at some point (Table 1). This Clinical Microbiology and Infectious Diseases. Published by practice was more common in geriatricians (97.2%) compared Elsevier Ltd. All rights reserved. to ID specialists (92.5%). Geriatricians were more likely to treat at least six patients per month by sc antibiotics (37% vs. 13.9% Keywords: Antibiotics, ceftriaxone, ertapenem, subcutaneous, of ID physicians). Forty geriatricians (14%) declared treating teicoplanin more than ten patients per month by sc antibiotics. The Original Submission: 30 July 2014; Revised Submission: 6 duration of sc antibiotics treatment was usually 4 to 14 days for November 2014; Accepted: 15 November 2014 285 participants (77.5%), and sometimes more than 2 weeks for Editor: M. Paul 45.3% of ID practitioners. Article published online: 23 November 2014 Ceftriaxone was the most prescribed antibiotic by the sc route. A majority of ID physicians reported administering ertapenem and teicoplanin by the sc route (70.9% and 80.2% respectively). Sc aminoglycosides were mostly prescribed by Corresponding author: E. Forestier, Service de Maladies Infec- tieuses, Centre Hospitalier, BP 1125, 73011 Chambery cedex, France geriatricians (40.9%). Sc amoxicillin was used by 56 participants E-mail: [email protected] (15.3%). Finally, some practitioners reported using sc cefepime

Clin Microbiol Infect 2015; 21: 370.e1–370.e3 Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rightsreserved http://dx.doi.org/10.1016/j.cmi.2014.11.017 CMI Forestier et al. Subcutaneously administered antibiotics 370.e2

TABLE 1. Subcutaneous antibiotics prescription patterns of Pain was the main adverse effect reported with sc injection French ID practitioners and geriatricians of antibiotics. Two hundred twenty-five practitioners (61.3%) “ ” “ ” ID practitioners Geriatricians Total reported that it occurred sometimes and 35 (9.5%) often. Skin necrosis and lack of efficacy were “sometimes” recorded, Pattern (n [ 86) (n [ 281) (n [ 367) respectively, by 47 (12.8%) and 73 (19.9%) prescribers of sc No. of patients treated by sc antibiotics (per month) antibiotics. <1 32 (37.2%) 30 (11%) 62 (16.9%) 1 to 5 41 (47.7%) 141 (50%) 182 (49.6%) 6 to 10 10 (11.6%) 65 (23%) 75 (20.4%) >10 2 (2.3%) 40 (14%) 42 (11.4%) DNP 1 (1.2%) 5 (2%) 6 (1.6%) Discussion Duration of sc antibiotic treatment (days) <4 3 (3.5%) 8 (3%) 1 (3%) 4 to 14 43 (50%) 242 (86%) 285 (77.5%) >14 39 (45.3%) 30 (11%) 69 18.8%) DNP 1 (1.2%) 1 (0%) 2 (0.5%) ID physicians and geriatricians seem to routinely prescribe Antibiotics used by sc route Amoxicillin 8 (9.3%) 48 (17.1%) 56 (15.3%) antibiotics by the sc route in France. These results must be Aminoglycosides 14 (16.3%) 115 (40.9%) 129 (35.1%) carefully interpreted given the declaratory and voluntary nature Ceftriaxone 85 (98.9%) 281 (100%) 366 (100%) Ertapenem 61 (70.9%) 61 (21.7%) 122 (33.2%) of our survey and the one quarter answer rate among the cli- Teicoplanin 69 (80.2%) 75 (26.7%) 144 (39.2%) Reason for resorting to sc route nicians from both societies. However, the participants worked Iv/im route contraindicated 85 (98.8%) 272 (96.8%) 357 (97.3%) Oral route contraindicated 79 (91.9%) 273 (97.2%) 352 (95.9%) in more than 160 different hospitals throughout the French Avoiding multiple 19 (22.1%) 141 (50.2%) 160 (43.6%) oral treatment territory, thus likely reflecting the current practice of a signif- Palliative care 68 (79.1%) 267 (95%) 335 (91.3%) Facilitating hospital discharge 85 (94.2%) 170 (60.5%) 255 (69.5%) icant proportion of ID and geriatric physicians. Reason for not resorting to sc route No pharmacokinetic 48 (55.8%) 171 (60.9%) 219 (59.7%) The sc route is frequently used to administer treatments data published (hydration, midazolam, morphine succinate) in geriatric settings No marketing authorization 10 (11.6%) 97 (34.5%) 107 (29.2%) Serum monitoring 2 (2.3%) 9 (3.2%) 11 (3%) because it is technically less time-consuming for nurses, painless not available No previous iv treatment 28 (32.6%) 25 (8.9%) 53 (14.4%) and safer to perform compared to iv and im injection, while Other 6 (7%) 6 (2.1%) 12 (3.3%) DNP 17 (19.8%) 53 (18.9%) 70 (19.1%) keeping the advantages of parenteral infusion [2,3]. Thus, sc ID, infectious disease; DNP, did not pronounce; sc, subcutaneous; iv, intravenous; antibiotics are widely prescribed by French geriatricians im, intramuscular. because the elderly often have poor venous access, contrain- dications to the im route (notably anticoagulants) and unpre- dictable oral intake and intestinal absorption, especially in (n = 9), imipenem (n = 6), piperacillin–tazobactam (n = 2), circumstances like palliative care. For ID physicians who deal amoxicillin-clavulanic acid (n = 2), ceftazidime (n = 1) and with infections requiring long-term parenteral treatment (such doripenem (n = 1). as bone and joint infections or endocarditis) and multidrug- The main reason for resorting to the sc route was in the case resistant bacteria, the sc route allows extended parenteral of unavailable oral, intravenous (iv) or intramuscular (im) antibiotic treatment and early hospital discharge while avoiding routes, especially during palliative care. Geriatricians were the infectious and thrombotic risks of a central venous access. more prone than ID physicians (50.2% vs. 22.1%) to prescribe In addition, sc administration may well suit the pharmacody- antibiotics sc to avoid oral polypharmacy. Conversely, 94.2% of namics of time-dependent antibiotics (such as ertapenem and ID specialists vs. 60.2% of geriatricians reported using the sc teicoplanin), leading to more stable serum concentration over route to facilitate hospital discharge. Two hundred nineteen 24 hours. practitioners (59.7%) declared that they do not prescribe an- However, sc antibiotics present numerous limitations which tibiotics sc in the absence of available pharmacokinetic and/or may be insufficiently considered by physicians. Ceftriaxone has a clinical data. Unlike geriatricians (8.9%), ID specialists (32.6%) marketing authorization for that route, but published evidence were more prone to use the sc route only after an iv loading on its efficacy and safety is limited [4–7]. Administering amino- dose. Conversely, 34.5% of geriatricians vs. 11.6% of ID phy- glycosides sc is formally contraindicated by recently published sicians said they did not use the sc route in the absence of a French guidelines because of uncertain efficacy and risk of skin marketing authorization available for this route for a given necrosis (http://ansm.sante.fr/Dossiers/Antibiotiques/Autres- antibiotic. However, 43% of these practitioners used amoxi- recommandations-impliquant-des-antibiotiques/(offset)/8). Data cillin, ertapenem and/or teicoplanin sc. The lack of serum on sc ertapenem and teicoplanin are promising but sparse monitoring available for a molecule was an obstacle to use the [8–12]. Several antibiotics, especially amoxicillin, are adminis- sc route for only 11 practitioners (3%). Other reasons reported tered by the sc route despite the absence of any published data. against sc route were treatment with a vitamin K antagonist, Finally, adverse effects like skin necrosis and lack of efficacy re- edema, severe skin disease and severe sepsis. ported in our survey could be serious.

Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved, CMI, 21, 370.e1–370.e3 370.e3 Clinical Microbiology and Infection, Volume 21 Number 4, April 2015 CMI

Conclusion [3] Fonzo-Christe C, Vukasovic C, Wasilewski-Rasca AF, Bonnabry P. Subcutaneous administration of drugs in the elderly: survey of practice and systematic literature review. Palliat Med 2005;19:208–19. [4] Borner K, Lode H, Hampel B, Pfeuffer M, Koeppe P. Comparative Administering antibiotics via the sc route appears to be com- pharmacokinetics of ceftriaxone after subcutaneous and intravenous mon among ID and geriatrics specialists in France, and it seems administration. Chemotherapy 1985;31:237–45. to answer a real need in their daily practice. Given the absence [5] Bricaire F, Castaing JL, Pocidalo JJ, Vilde JL. Pharmacokinetics and of any evidence on efficacy and safety, this practice cannot be tolerance of ceftriaxone after subcutaneous administration. Pathol Biol (Paris) 1988;36:702–5. fi recommended to date, and it should be de nitively banned for [6] Gauthier D, Schambach S, Crouzet J, Sirvain S, Fraisse T. Subcutaneous aminoglycosides. However, it may deserve further research for and intravenous ceftriaxone administration in patients more than 75 – time-dependent antibiotics because it could offer several ad- years of age. Med Mal Infect 2014;44:275 80. [7] Harb G, Lebel F, Battikha J, Thackara JW. Safety and pharmacoki- vantages compared to other parenteral routes. An expert netics of subcutaneous ceftriaxone administered with or without group should be urgently created to review the evidence, make recombinant human hyaluronidase (rHuPH20) versus intravenous clear national recommendations and plan further pharmacoki- ceftriaxone administration in adult volunteers. Curr Med Res Opin 2010;26:279–88. netic and clinical studies to validate (or not) this practice. [8] Frasca D, Marchand S, Petitpas F, Dahyot-Fizelier C, Couet W, Mimoz O. Pharmacokinetics of ertapenem following intravenous and subcutaneous infusions in patients. Antimicrob Agents Chemother Transparency declaration 2010;54:924–6. [9] Ferry T, Sénéchal A, Gagnieu MC, Boibieux A, Laurent F, Perpoint T, et al. Prolonged subcutaneous high dose (1 g bid) of ertapenem as All authors report no conflicts of interest relevant to this salvage therapy in patients with difficult-to-treat bone and joint infec- – article. tion. J Infect 2012;65:579 82. [10] Forestier E, Gros S, Peynaud D, Levast M, Boisseau D, Ferry-Blanco C, et al. Ertapenem administered intravenously or subcutaneously for urinary tract infections caused by ESBL producing enterobacteriacea. References Med Mal Infect 2012;42:440–3. [11] Barbot A, Venisse N, Rayeh F, Bouquet S, Debaene B, Mimoz O. Pharmacokinetics and pharmacodynamics of sequential intravenous [1] Robelet A, Caruba T, Corvol A, Bégué D, Gisselbrecht M, Saint- and subcutaneous teicoplanin in critically ill patients without vaso- Jean O, et al. Antibiotics given subcutaneously to elderly. Presse Med pressors. Intensive Care Med 2003;29:1528–34. 2009;38:366–76. [12] Carpentier E, Romeo B, El Samad Y, Geslin-Lichtenberger L, [2] Remington R, Hultman T. Hypodermoclysis to treat dehydration: a Maingourd Y, Tourneux P. Subcutaneous teicoplanin for children with review of the evidence. J Am Geriatr Soc 2007;55:2051–5. infectious endocarditis. Arch Pediatr 2013;20:775–8.