akinohanayuki ブログ

学位を持っても、センスのない、感染制御専門薬剤師のブログ.  I have Ph.D. but less sense ID pharmacist.

Switch Therapy  ざっくり メモ

Switch Therapy または、intravenous to oral switch therapy (IVOST) 

Antimicrobial stewardship programの1つとしても有名で、薬剤師参画が求められています。

Switch Therapy 優先順位は、もっと高くなるはずです。
Switch Therapyはキノロン促販になることです
キノロンSwitch すると抗菌スペクトルはエスカレーションになることが多いです。
安易キノロン以外のSwitch Therapyを模索したいです。
糖尿病が既往にある肝膿瘍のSwitch Therapyは、消化器科の先生と毎回悩みます。
ESBLs 前立腺炎、さらに悩みます。FOMでいいのか....などなど
「ざっくり」 ハンドリサーチ



まずは、review and meta-analysis

Medscape.  Updated: Jan 09, 2015

Intravenous-to-Oral Switch Therapy

Free.  良くまとまっています。

Switch therapy is possible with various oral antibiotics. Antibiotics ideal for intravenous-to-oral (IV-to-PO) switch programs include 
chloramphenicol, clindamycin, metronidazole, trimethoprim-sulfamethoxazole, fluconazole, itraconazole, voriconazole, doxycycline, minocycline, levofloxacin, moxifloxacin, and linezolid
Numerous factors must be weighed before switching hospitalized patients from intravenous to oral antibiotics. In a study by Halm et al (J Gen Intern Med. 2001 Sep. 16(9):599-605. ) the following factors were rated as very important to the antibiotic conversion decision
  • Absence of suppurative infection (93%)
  • Ability to maintain oral intake (79%)
  • Respiratory rate at baseline (64%)
  • No positive blood culture findings (63%)
  • Normal temperature (62%)
  • Oxygenation at baseline (55%)
  • Mental status at baseline (50%)
physicians believed a typical patient could be converted to oral therapy were as follows
  • Temperature of less than or equal to 100°F (37.8°C)
  • Respiratory rate of less than or equal to 20 breaths per minute
  • Heart rate of less than or equal to 100 beats per minute
  • Systolic blood pressure of 100 mm Hg or higher
  • Room air oxygen saturation of 90% or higher
safely 4 criteria
(Pharmacotherapy. 2001 Jul. 21(7 Pt 2):79S-82S.) 
  • cough and respiratory distress improve
  • fever abates for at least 8 hours
  • the WBC count is returning to within the   reference range
  •  the patient can take drugs orally. 

J Pharmacol Pharmacother 2014 Apr; 5(2):83-7.

Switch over from intravenous to oral therapy: A concise overview.


Majority of the patients admitted to a hospital with severe infections are initially started with intravenous medications. Short intravenous course of therapy for 2-3 days followed by oral medications for the remainder of the course is found to be beneficial to many patients. This switch over from intravenous to oral therapy is widely practiced in the case of antibiotics in many developed countries. Even though intravenous to oral therapy conversion is inappropriate for a patient who is critically ill or who has inability to absorb oral medications, every hospital will have a certain number of patients who are eligible for switch over from intravenous to oral therapy. Among the various routes of administration of medications, oral administration is considered to be the most acceptable and economical method of administration. The main obstacle limiting intravenous to oral conversion is the belief that oral medications do not achieve the same bioavailability as that of intravenous medications and that the same agent must be used both intravenously and orally. The advent of newer, more potent or broad spectrum oral agents that achieve higher and more consistent serum and tissue concentration has paved the way for the popularity of intravenous to oral medication conversion. In this review, the advantages of intravenous to oral switch over therapy, the various methods of intravenous to oral conversion, bioavailability of various oral medications for the switch over program, the patient selection criteria for conversion from parenteral to oral route and application of intravenous to oral switch over through case studies are exemplified.

Curr Med Res Opin. 2008 Dec;24(12):3423-34.

Early switch to oral versus intravenous antimicrobial treatment for hospitalized patients with acute pyelonephritis: a systematic review of randomized controlled trials.


 Eight RCTs (6 in children) were eligible for inclusion. In 5 RCTs the intravenous antibiotic treatment arms were not switched to oral treatment until the end of the study while in the remaining 3 RCTs the intravenous arms were switched late to oral treatment (after 5-10 days). Data regarding the incidence of renal scars, microbiological eradication, clinical cure, reinfection, persistence of acute pyelonephritis, and adverse events were provided in 4 (all pediatric trials), 6 (4 pediatric), 4 (2 pediatric), 5 (3 pediatric), 3 (1 pediatric), and 5 RCTs (3 pediatric), respectively. There were no differences regarding the above outcomes between the two compared treatment regimens in either pediatric or adult populations

 Drugs. 2008;68(17):2469-81.

 Early switch to oral treatment in patients with moderate to severe community-acquired pneumonia: a meta-analysis.



Six RCTs including 1219 patients fulfilled the criteria for inclusion in the meta-analysis. Treatment success was not different between early switch to oral treatment and intravenous only treatment groups in both intention to treat (odds ratio [OR] 0.76; 95% CI 0.36, 1.59) and clinically evaluable patients (OR 0.92; 95% CI 0.61, 1.39). Mortality and recurrence of CAP were not different (OR 0.81; 95% CI 0.49, 1.33 and OR 1.81; 95% CI 0.70, 4.72, respectively), while duration of hospitalization was shorter (weight mean difference -3.34; 95% CI -4.42, -2.25) and drug-related adverse events were fewer in the early switch group (OR 0.65; 95% CI 0.48, 0.89). Findings were similar in patients with severe CAP.


Arch. Intern. Med. 2001 Mar 12; 161(5):722-7.

Early switch and early discharge strategies in patients with community-acquired pneumonia: a meta-analysis.
From 1794 titles identified, 121 articles were reviewed. We identified 10 prospective, interventional, community-acquired pneumonia-specific studies that evaluated length of stay (LOS). Nine studies applied an early switch from parenteral to oral antibiotic criteria. Six different criteria for switching were applied in the 9 studies. Five of the studies that applied early switch criteria also applied separate criteria for early discharge. Six studies applied an early switch and early discharge strategy to an intervention and control group, and 5 of these provided SD values for LOS. The mean change in LOS was not significantly (P =.05) reduced in studies of early switch and early discharge (-1.64 days; 95% confidence interval, -3.30 to 0.02 days). However, when the 2 studies in which the recommended LOS was longer than the control LOS were excluded from the analysis, the mean change in LOS was reduced by 3 days (-3.04 days; 95% confidence interval, -4.90 to -1.19 days). Studies did not reveal significant differences in clinical outcomes between the intervention and control groups.





 J Med Assoc Thai 2015 Sep; 98(9):858-63.
Comparison between the Efficacy of Switch Therapy and Conventional Therapy in Pediatric Community-Acquired Pneumonia.
There were no significant differences in age, sex, clinical presentations, and antibiotics provided between the two groups. A statistically significant reduction in length of hospital stay was found in the the switch therapy (SWT) group (P = 0.019), whereas the readmission rate for both groups was not significantly different (p = 0.66). Morbidity and mortality were not found in either groups. The SWT group demonstrated non-inferior efficacy comparing to control group (difference 20%; p<0. 001).
Dig. Dis. Sci. 2014 Jun 5.
Early Oral Antibiotic Switch Compared with Conventional Intravenous Antibiotic Therapy for Acute Cholangitis with Bacteremia.
There were no statistically significant differences between the two groups in baseline characteristics, clinical and laboratory index, severity of acute cholangitis, bacteria isolated from blood cultures, and clinical outcomes. The rate of eradication of bacteria was 93.1 % in group A and 93.3 % in group B, respectively (p = 0.97). Using non-inferiority tests, the rate of eradication of bacteria in group A was not inferior to that in group B (95 % CI -0.13 to 0.14, p = 0.97). There was no statistically significant difference in the recurrence of acute cholangitis and a 30-day mortality rate between the two groups.

Int J Antimicrob Agents. 2014 Jul;44(1):56-64.

Antibiotic treatment patterns across Europe in patients with complicated skin and soft-tissue infections due to meticillin-resistant Staphylococcus aureus: a plea for implementation of early switch and early discharge criteria
 Of 1502 patients, 1468 received MRSA-targeted therapy. Intravenous-to-oral switch rates ranged from 2.0% to 20.2%, i.v. length of therapy from 10.1 to 18.6 days and hospital length of stay (LoS) from 15.2 to 25.0 days across Europe. Of 341 sites, 82.9% had antibiotic steering committees, 23.7% had i.v.-to-oral switch antibiotic protocols and 12.9% had ED protocols for MRSA cSSTI. ES and ED eligibility ranged from 12.0% (Slovakia) to 56.3% (Greece) and from 10% (Slovakia) to 48.2% (Portugal), respectively. Potential cost savings per ED-eligible patient ranged from €414 (Slovakia) to €2703 (France). 
Clin Microbiol Infect. 2014 Oct;20(10):993-1000.

Pan-European early switch/early discharge opportunities exist for hospitalized patients with methicillin-resistant Staphylococcus aureus complicated skin and soft tissue infections.



 This retrospective observational medical chart review study enrolled 342 physicians across 12 European countries who collected data from 1542 patients with documented MRSA cSSTI who were hospitalized (July 2010 to June 2011) and discharged alive (by July 2011). Data included clinical characteristics and outcomes, hospital length of stay (LOS), MRSA-targeted IV and oral antibiotic use, and ES and ED eligibility according to literature-based and expert-validated criteria. The most frequent initial MRSA-active antibiotics were vancomycin (50.2%), linezolid (15.1%), clindamycin (10.8%), and teicoplanin (10.4%). Patients discharged with MRSA-active antibiotics (n = 480) were most frequently prescribed linezolid (42.1%) and clindamycin (19.8%). IV treatment duration (9.3 ± 6.5 vs. 14.6 ± 9.9 days; p <0.001) and hospital LOS (19.1 ± 12.9 vs. 21.0 ± 18.2 days; p 0.162) tended to be shorter for patients switched from IV to oral treatment than for patients who received IV treatment only. Of the patients, 33.6% met ES criteria and could have discontinued IV treatment 6.0 ± 5.5 days earlier, and 37.9% met ED criteria and could have been discharged 6.2 ± 8.2 days earlier.

J. Infect. Chemother. 2013 Dec; 19(6):1035-41.
Early switch therapy from intravenous sulbactam/ampicillin to oral garenoxacin in patients with community-acquired pneumonia: a multicenter, randomized study in Japan.
The switch from intravenous to oral antibiotic therapy is recommended for treating hospitalized patients with community-acquired pneumonia (CAP). We performed a multicenter, randomized study to assess the benefit of switching from intravenous sulbactam/ampicillin (SBT/ABPC) to oral garenoxacin (GRNX) in patients with CAP. Among adult CAP patients who must be hospitalized for intravenous antibiotic treatment, those with Pneumonia Patient Outcomes Research Team (PORT) scores of II-IV (mild to moderate) were initially treated with intravenous SBT/ABPC (6 g/day) for 3 days. A total of 108 patients who fulfilled the inclusion criteria (improved respiratory symptoms, CRP < 15 mg/dl, adequately improved oral intake, fever ≤ 38 °C for ≥ 12 h), were divided into two groups based on the antibiotic administered, the GRNX (switch to GRNX 400 mg/day) and SBT/ABPC groups (continuous administration of SBT/ABPC), for 4 days. Improvement in clinical symptoms, chest radiographic findings, and clinical effectiveness were evaluated by a central review board. Improvement in clinical symptoms was 96.3 and 90.2% in the GRNX and SBT/ABPC groups, respectively. Improvement in chest radiographic findings was 94.4 and 90.2% and clinical effectiveness was 94.4 and 90.2% in the GRNX and SBT/ABPC groups, respectively. Microbiological efficacy was 90.9 and 69.2% in the GRNX and SBT/ABPC groups, respectively. There were no significant differences between the groups. Converting to GRNX was as effective as continuous SBT/ABPC treatment in mild to moderate CAP patients in whom initial intravenous antibiotic treatment was successful.
BMC Infect. Dis. 2012.:159.
Switch therapy in hospitalized patients with community-acquired pneumonia: tigecycline vs. levofloxacin.
In the clinically evaluable (CE) population, 138 patients were treated with IV tigecycline and 156 were treated with IV levofloxacin. The proportion of the population that met switch therapy criteria was 67.4% (93/138) for tigecycline and 66.7% (104/156) for levofloxacin. The proportion that actually switched to oral therapy was 89.9% (124/138) for tigecycline and 87.8% (137/156) for levofloxacin. Median time to actual switch therapy was 5.0 days each for tigecycline and levofloxacin. Clinical cure rates for patients who switched were 96.8% for tigecycline and 95.6% for levofloxacin. Corresponding cure rates for those that met switch criteria were 95.7% for tigecycline and 92.3% for levofloxacin.

J Antimicrob Chemother. 2012 Mar;67(3):756-62. 

 Implementation of intravenous to oral antibiotic switch therapy guidelines in the general medical wards of a tertiary-level hospital in South Africa.



 Implementation of the IVOST guideline was successful in increasing (P<0.0005) the number of patients switched from 16% (19/119) pre-implementation to 43.9% (47/107) immediately after implementation; however, the change was not sustained 3 months after implementation (20.8%; 25/120). The intervention was also successful in decreasing the overall duration of iv therapy (P<0.0005) from 7.2 ± 3.5 days pre-implementation to 5.2 ± 3.0 days immediately post-implementation. The change was not sustained 3 months after implementation (6.5 ± 3.5 days).


J Antimicrob Chemother. 2011 Oct;66(10):2405-8.

Role of early intravenous to oral antibiotic switch therapy in the management of prosthetic hip infection treated with one- or two-stage replacement.



 In 24 months, 19 patients underwent two-stage THR for infection, of which 17 were treated with oral antibiotics after a median of 14 days initial iv antibiotics. None relapsed. Four patients underwent one-stage THR and had 12-20 days iv then 6-26 weeks oral antibiotics with no relapse.


Int J Clin Pharm 2011 Apr; 33(2):208-14.

Implementing a pharmacist-led sequential antimicrobial therapy strategy: a controlled before-and-after study.


The study was conducted in a 753-bed academic hospital in Ireland.

The study was prospective and of controlled before and after design. Patients admitted under the care of a medical consultant were screened for inclusion. The study was divided into pre-intervention and post-intervention phases. Patients admitted and prescribed IV antimicrobials were enrolled into either a study group or control group. Post-intervention, the intervention to the study group consisted of application of stickers and criteria for switch to oral antimicrobial therapy to the drug chart. Pre-intervention in the study group and in both phases in the control group, conventional practice of clinical pharmacists reviewing drug charts and contacting prescribers to discuss a switch to an oral antimicrobial continued. The duration of intravenous treatment, the timeliness of switch to oral therapy, length of stay and cost savings were measured.

The duration of intravenous antimicrobial therapy in the pre-intervention and post-intervention phases in both study and control groups.

Pre-intervention, 85 courses of IV antimicrobials were prescribed to study group patients, compared to 60 in the control group. Post-intervention, there were 92 courses in the study group and 53 in the control group. The duration of IV antimicrobial treatment reduced significantly in the study group post-intervention, compared to the control group (P = 0.02). The timeliness of the switch also improved significantly in the study group post-intervention (P = 0.017). No improvement occurred in the control group. The median length of stay was not reduced post-intervention. Antimicrobial costs reduced by a mean of €6.41 in the study group post-intervention.


Antimicrob. Agents Chemother.2009 Sep; 53(9):3782-92.
Intravenous doripenem at 500 milligrams versus levofloxacin at 250 milligrams, with an option to switch to oral therapy, for treatment of complicated lower urinary tract infection and pyelonephritis.
For the microbiologically evaluable patients (n = 545), the microbiological cure rates were 82.1% and 83.4% for doripenem and levofloxacin, respectively (95% confidence interval [CI] for the difference, -8.0 to 5.5%); in the microbiological modified intent-to-treat cohort (n = 648), the cure rates were 79.2% and 78.2%, respectively. Clinical cure rates at the test of cure  visit were 95.1% in the doripenem arm and 90.2% in the levofloxacin arm (95% CI around the difference in cure rates [doripenem cure rate minus levofloxacin cure rate], 0.2% to 9.6%). 

J Antimicrob Chemother. 2008 Aug;62(2):424-5.

 Successful oral therapy switch to trimethoprim/sulfamethoxazole in the case of an Enterococcus faecium liver abscess.



Ann Thorac Surg. 2007 Jul;84(1):87-91.

Early switch from vancomycin to oral linezolid for treatment of gram-positive heart valve endocarditis.


Fourteen patients were identified; average age was 52 +/- 16 years. There were 10 (85%) and 2 (15%) cases of native and prosthetic valve endocarditis, respectively. Patients were operated on 3 to 10 days after diagnosis. There were no cases of operative mortality. Mean follow-up was 20.8 +/- 7.0 months. Two (14%) patients died of noncardiac causes during follow-up. The mean intensive care unit length of stay was 3.1 +/- 2.3 days, and mean hospital length of stay was 10.5 +/- 3.4 days. No cases of recurrent endocarditis or periprosthetic leakage were observed.

Respirology. 2007 Jan;12(1):111-6.

 Early switch to oral antibiotics and early discharge guidelines in the management of community-acquired pneumonia.



 One hundred and twenty-five patients in the prospective group were compared to 100 patients in the controls. Baseline characteristics were similar between the comparison groups. Both the mean duration of i.v. antibiotics used (3.38 +/- 0.22 vs. 3.99 +/- 0.28 days, P = 0.03) and LOS (7.62 +/- 0.60 vs. 8.36 +/- 0.55 days, P = 0.04) were significantly shorter in the prospective group. Thirty-day readmission rate was 6% and patient self-reported overall satisfaction was 93.9% in those who were followed up.


BMJ 2006 Dec 9; 333(7580):1193.
Effectiveness of early switch from intravenous to oral antibiotics in severe community acquired pneumonia: multicentre randomised trial.
302 patients were randomised (mean age 69.5 (standard deviation 14.0), mean pneumonia severity score 112.7 (26.0)). 37 patients were excluded from analysis because of early dropout before day 3, leaving 265 patients for intention to treat analysis. Mortality at day 28 was 4% in the intervention group and 6% in the control group (mean difference 2%, 95% confidence interval -3% to 8%). Clinical cure was 83% in the intervention group and 85% in the control group (2%, -7% to 10%). Duration of intravenous treatment and length of hospital stay were reduced in the intervention group, with mean differences of 3.4 days (3.6 (1.5) v 7.0 (2.0) days; 2.8 to 3.9) and 1.9 days (9.6 (5.0) v 11.5 (4.9) days; 0.6 to 3.2), respectively.
Aliment. Pharmacol. Ther. 2006 Jan 1; 23(1):75-84.
Switch therapy with ciprofloxacin vs. intravenous ceftazidime in the treatment of spontaneous bacterial peritonitis in patients with cirrhosis: similar efficacy at lower cost.
Resolution of infection was achieved in 46/55 patients treated with ceftazidime (84%) and in 49/61 patients treated with ciprofloxacin (80%, P = N.S.). An intravenous-oral step-down schedule was possible in 50/61 patients (82%) who received ciprofloxacin; 45/61 patients (74%) were discharged before the end of antibiotic treatment and completed it at home. The mean saving per patient due to the reduction of hospital stay in the ciprofloxacin group was 1150 . Type 1 hepatorenal syndrome was treated successfully in 12/19 patients (63%). As a consequence, the in-hospital mortality rate due to infection was 10%.
Am J Med Qual 2005 Jan-Feb; 20(1):15-21.
Getting physicians to make "the switch": the role of clinical guidelines in the management of community-acquired pneumonia.
Physicians were surveyed before and after guideline adoption. Community-acquired pneumonia guideline implementation increased physician awareness of American Thoracic Society recommendations (5% to 40%) and use of switch therapy (60% to 86%). Such use resulted in decreased overall length of stay from 3.6 to 2.4 days (P < .05) and from 2.91 to 2.41 days (P < .05) among early-switch candidates. 

Arch. Intern. Med. 2004 Jun 14; 164(11):1206-12.

Improving the process of antibiotic therapy in daily practice: interventions to optimize timing, dosage adjustment to renal function, and switch therapy. 


In the preintervention and postintervention periods, 247 and 250 patients were enrolled, receiving 563 and 598 antibiotic prescriptions, respectively. The mean time from the order to first dose at the wards improved from 2.7 to 1.7 hours in potentially severe cases (P =.003). Dosage adjustment to renal function remained unchanged at 45% vs 52% (P =.09) of cases where necessary. Switching of therapy from intravenous to oral improved from 46% to 62% (P =.03) and was performed a mean of 1.6 days earlier (P =.002). Streamlining was performed correctly in most cases, and thus no interventions were necessary.

Chest 2002 Oct; 122(4):1271-9.
Cost-effectiveness of IV-to-oral switch therapy: azithromycin vs cefuroxime with or without erythromycin for the treatment of community-acquired pneumonia.
The clinical success and adverse event rates and antibiotic-related length of stay were 78%, 11.8%, and 5.8 days for the azithromycin group and 75%, 20.7%, and 6.4 days for the group receiving cefuroxime with or without erythromycin, respectively. Geometric mean treatment costs were 4,104 US dollars (95% confidence interval [CI], 3,874 to 4,334 US dollars) for the azithromycin group, and 4,578 US dollars (95% CI, 4,319 to 4,837 US dollars) for the group receiving cefuroxime with or without erythromycin (p = 0.06). The cost-effectiveness ratios were 5,265 US dollars per expected cure for the azithromycin group, and 6,145 US dollars per expected cure for group receiving cefuroxime with or without erythromycin (p = 0.05).
Am. J. Med. 2001 Oct 1; 111(5):367-74.
Efficacy and safety of oral and early-switch therapy for community-acquired pneumonia: a randomized controlled trial.
Among patients with nonsevere pneumonia, there were no deaths in the oral treatment group, and one death (2%) in the parenteral treatment group (95% confidence interval [CI] for between-group [oral minus parenteral] difference: -7% to 2%, P = 0.3). The time to resolution of morbidity was < or =5 days in 34 (83%) patients in the oral treatment group and 39 (88%) patients in the parenteral treatment group (P = 0.5); there were treatment failures in 4 (10%) patients in the oral treatment group and 14 (32%) patients in the parenteral treatment group (P = 0.02). Among patients with severe pneumonia, there was one (2%) death in the early-switch group and no deaths in the full course of parenteral antibiotics groups (95% CI for between-group [early switch vs. full course] difference: -2% to 6%, P = 0.5). The time to resolution of morbidity was < or =5 days in 38 (79%) patients in the early-switch group and 41 (75%) in the full-course group (P = 0.3). There were 12 (25%) treatment failures in the early-switch group and 13 (24%) in the full-course group (P = 0.9). There were fewer adverse events in the oral and early-switch groups, primarily due to lower rates of infusion-related phlebitis. Significant cost savings, mainly due to a shorter hospitalization, occurred among patients with severe pneumonia in the early-switch group.

Arch Intern Med. 1999 Nov 8;159(20):2449-54.

 Early switch from intravenous to oral antibiotics and early hospital discharge: a prospective observational study of 200 consecutive patients with community-acquired pneumonia.


 Early switch to oral antibiotics (within the first 3 days of hospitalization) was performed in 133 patients (67%). Clinical failure was documented in 1 patient. Early switch and early discharge was performed in 88 patients (44%). The mean length of hospital stay for this group was 3.4 days. The most common reason for prolonged hospitalization after the switch to oral antibiotics was the need for diagnostic workup. More than 95% of patients were satisfied with the care they had received.


Arch. Intern. Med. 1995 Jun 26; 155(12):1273-6.
Early switch from intravenous to oral cephalosporins in the treatment of hospitalized patients with community-acquired pneumonia.
Of the 120 patients enrolled, 75 (62%) had clinical data evaluated. Long-term follow-up showed that 74 patients (99%) were cured; one patient required readmission for further intravenous therapy. Mean duration of hospital stay was 4 days.