Practice of switch from intravenous to oral antibiotics

The appropriate use of antibiotics depends on the selection of an agent capable of achieving a desired serum concentration to target the presumed organism at the site of infection with an acceptable safety profile (Burke 2003; Davey et al. 2006). Inappropriate and unnecessary antimicrobial usage leads to an increase in healthcare costs and pathogen resistance (Spellberg et al. 2008).

Antimicrobial Stewardship Programs (ASPs) have been developed to limit unnecessary antimicrobial use through reassessment of diagnosis and therapy within 48 to 72 hours, streamlining/de-escalation of antibiotics based on culture/sensitivity data, and the use of antibiotics for the shortest duration needed (Petrak et al. 2003; Dellit et al. 2007). Clinical pharmacists, with the help of infectious disease (ID) team, have an integral role in a day-to-day practice for the judicious use of antibiotics within a short period of time thus promoting further patient safety (Septimus and Owens 2011; ASHP 2010).

Most of inpatients are prescribed intravenous (IV) antibiotics for an extended duration of therapy while an oral (PO) route is possible. Approximately one third of all inpatients initiated on IV antibiotics are eligible for switch to an oral equivalent (McLaughlin et al. 2005). Short intravenous course of therapy for 2–3 days followed by oral medications to complete the course of therapy is beneficial to many patients except in conditions of serious/life-threatening infections, in critically ill patients, or in the presence of contraindications to oral administration as in case of nothing per os (NPO) or comatose patients (Septimus and Owens 2011; ASHP 2010; Bond and Raehl 2005; Bailey et al. 1997; Fischer et al. 2003). Selected oral medication produces serum levels comparable to those achieved through IV form with equivalent clinical outcomes as reduction in the length of hospital stay (LOS) and the duration of IV therapy, along with fewer complications, less patient inconvenience, less healthcare costs and earlier hospital discharge (Septimus and Owens 2011; Lee et al. 2012; Sevinç et al. 1999).

IV to PO conversion guidelines, a component of ASPs, are implemented in hospitals of developed countries and constitute a strategy in daily practice, whereas few hospitals in Lebanon adopt these programs (Septimus and Owens 2011; Kuper 2008). Patients fulfilling the predefined criteria for switch are evaluated. These criteria are based on both drug and host factors (ASHP 2010). Drug factors include high degree of activity against presumed/ known pathogens, high oral bioavailability, low resistance potential, and tolerance with a good safety profile (McLaughlin et al. 2005). Host factors require sufficient absorption of an oral antibiotic with no impairment of gastrointestinal tract and stable clinical condition (Septimus and Owens 2011; Kuper 2008). Improvement of clinical status is evaluated according to temperature, white blood cell count, absence of signs of sepsis, as well as specific criteria for particular infections (Septimus and Owens 2011; Bond and Raehl 2005; Kuper 2008; Gross et al. 2001; Kuti et al. 2002).

There exist three types of IV to PO conversion therapy: sequential, switch and step-down therapies (Kuper 2008). A sequential therapy consists of converting from IV to PO agents with the same compound; a switch therapy is converting with an identical potency; and a step-down therapy is converting with a reduced potency (Kuper 2008). The choice of the type depends on the antimicrobials class and the availability of an oral equivalent (Septimus and Owens 2011).

Most of the studies conducted for the evaluation of IV to PO antimicrobial conversion were interventional studies (Bailey et al. 1997; Kuti et al. 2002; Davis et al. 2005; Ho et al. 2005; Yen et al. 2012; Halley 2000), but have been restricted to certain antibiotic classes (Fischer et al. 2003; Kuti et al. 2002; Davis et al. 2005; Ho et al. 2005; Yen et al. 2012; Pablos et al. 2005; Buyle et al. 2010; Marra et al. 2000) and certain medical conditions (Davis et al. 2005; Cunha 2001; Ramirez and Bordon 2001; Fine et al. 2003). All of which were mostly allocated in the USA (Davis et al. 2005; Galanter et al. 2010; Lau et al. 2011; Glemaud 2000; Fox et al. 2003), others were done in Canada (Ho et al. 2005; Marra et al. 2000; Frighetto et al. 1995; Malfair et al. 1996; Zamin et al. 1997), Ireland (Dunn et al. 2011, Al-Eidan et al. 1999, Chan et al. 1995), Spain (Castro-Guardiola et al. 2001; Martínez et al. 2000), Netherlands (Oosterheert et al. 2006) and Switzerland (Mertz et al. 2009; Senn et al. 2004). These studies demonstrated comparable clinical efficacy rates without serious adverse events and improvements in therapeutic and financial outcomes (Fischer et al. 2003; Ho et al. 2005; Galanter et al. 2010).

The aim of the study was to evaluate the practice of switching from IV to PO antibiotics based on predefined eligibility criteria and its impact on clinical outcomes as the duration of IV antibiotic therapy and LOS, and to assess the correlation between the type of conversion and antibiotic classes.

This study was done on the Lebanese population where there is a need for unified local guidelines to the physicians and clinical pharmacists to aid in the conversion from IV to PO route when the condition of the patient has improved after few days of hospital admission. Various studies covered IV to PO conversion and their implications in clinical practice as the reduction of the prolonged use of IV antimicrobials and shortening of the LOS. The present study was not designed to prove that an early switch to PO therapy has the same efficacy as a full IV course.

Most of the admitted patients, who are initially prescribed IV antibiotics, can be switched to an appropriate PO formulation once the clinical stability markers are met, provided that the total course of therapy duration is completed. Using the defined criteria for IV to PO switch, two-third of the included patients in the study were not switched to PO therapy, despite improvements in clinical signs of infection. The number of patients that were switched to PO therapy could have been underestimated since the study design did not follow up discharged patients. In the Lebanese practice, patients are converted to PO antibiotic therapy once discharged home, although a 24 hour-period after switch is required for patient’s monitoring before discharge. Other possible barriers to a timely switch strategy perceived by the study results include unfamiliarity with guideline recommendations, misconceptions or lack of outcome expectancy. These barriers were also reflected by the study results of Schouten et al. (Schouten et al. 2007) and Halm et al. (Halm et al. 2001). Physicians were not aware of the existence of clear guidelines on the adequate timing of the switch. Indeed, participating hospitals did not provide these guidelines through booklets or educational sessions and did not adopt ASPs that may be applied in few centers in Lebanon.

Modifications in IV antibiotics were done in one-third of the antibiotic courses; interventions for switch were either through discontinuation of therapy or conversion to the alternative oral drug depending on the antibiotic class that was prescribed. Administered antibiotic courses of therapy that were switched to a suitable PO formulation were few and involved mostly fluoroquinolnes, macrolides and metronidazole classes probably because these antibiotics are available in both PO and IV formulations where sequential conversion type is used. Whereas the number of antibiotic courses on β-lactams (specifically third-generation cephalosporins) switched to a PO alternative was rare, and modification was done through discontinuation of the drug on the day of clinical stability rather than switching to PO therapy, similarly to the observation done by Hunter and Dormaier (Hunter and Dormaier 1995). As a further illustration about the switch, drugs as ceftriaxone with no definitive oral equivalent; its conversion to a PO agent is done through step-down conversion therapy, which was minimally done in this study.

The mean number of days to clinical stability and therefore the time for switch in this study was 3.81 days, correlated with the results of previous studies (Mertz et al. 2009; Senn et al. 2004; Athanassa et al. 2008) that also reported the appropriate time for IV therapy to be reassessed between 2.0 - 4.0 days. In this study, the mean length of IV therapy was around 7 days for non-converted patients compared to around 4 days for the converted ones. However, a reduction in the LOS was not observed, similarly to Laing et al. (Laing et al. 1998) even though the duration of IV therapy shortened in patients who were converted which correlates with the results of previous studies (Mertz et al. 2009; Laing et al. 1998).

Antibiotic resistance is directly related to the excessive use of antibiotics. Previous studies evaluating antibiotic use in hospitals have shown that up to 50% of prescriptions can be inappropriate (Goldmann et al. 1996; McGowan 1994; Kollef et al. 1997; Thuong et al. 2000). Hence limiting the misuse of antibiotics may be an important intervention for reducing levels of resistance. Results of the study confirm the tendency of physicians to prescribe broad-spectrum antibiotic therapy empirically with β-lactams mainly third-generation cephalosporins followed by fluoroquinolones the most widely used antibiotic classes among assessed patients. Therefore, improving appropriateness of therapy at the time of initial empirical prescribing is a difficult challenge associated with many organizational requirements and governed by the hospital policy.

The results of this evaluation highlighted the need of a structured approach and clear guidelines to appropriately prescribe antibiotics and review the therapeutic decisions including assessment for improvement in patient’s clinical status for antibiotic conversion from IV to PO therapy in daily practice. Further studies are needed to assess physician’s knowledge, beliefs, and acceptance of the switch over from IV to PO therapy in order to establish an effective and unified guideline for IV to PO conversion and consequently its implementation through team approach. This study did not measure the reduction in complications from the IV to PO switch since it was a retrospective observational study. Hence, this raises the need for a future prospective research with a pharmacist-involved intervention.