Eur J Clin Microbiol Infect Dis DOI 10.1007/s10096-014-2113-z
LETTER TO THE EDITOR
Pharmacoeconomic advantages of oral minocycline for the therapy of methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections (SSTIs) B. A. Cunha
Received: 2 April 2014 / Accepted: 7 April 2014 # Springer-Verlag Berlin Heidelberg 2014
Dear Editor, I read with great interest the article by Dr. Seaton et al. regarding the economic aspects of methicillin-resistant Staphylococcus aureus (MRSA) therapy for complicated skin and soft tissue infections (SSTIs) [1]. Their interesting and well executed paper merits additional comments and a North American perspective. The authors’ article on MRSA SSTIs discussed the costs of intravenous (IV) antibiotic regimens and the cost savings of early in-house discharge using IV to oral (PO) switch therapy and outpatient parenteral antibiotic therapy (OPAT) using linezolid, rifampicin, or doxycycline [2–7]. MRSA SSTIs mainly present as cutaneous abscesses, in contrast to group A SSTIs, that present as cellulitis [8, 9]. The cornerstone of therapy for MRSA SSTI cutaneous abscesses is incision and drainage. Antimicrobial therapy is adjunctive to prevent bacteremia and further extension of the MRSA SSTI [8]. The cost of IV antibiotics is usually substantially higher than the equivalent PO dose [1–3]. On the basis of drug acquisition costs alone, it is obvious that IV to PO switch therapy is much less expensive than IV therapy to the healthcare system [6, 7, 10]. Not only are antibiotic costs less in IV to PO switch programs, but the patients’ length of stay (LOS) is also decreased with earlier discharge on PO therapy [11]. Non-critically ill patients with serious systemic infections may also be effectively managed with oral antibiotic therapy alone [12–15]. Physicians lacking IV to PO switch experience are often reluctant to treat hospitalized patients B. A. Cunha (*) Infectious Disease Division, Winthrop-University Hospital, 222 Station Plaza North (Suite #432), Mineola, NY 11501, USA e-mail: [email protected] B. A. Cunha School of Medicine, State University of New York, Stony Brook, NY, USA
using PO antibiotics alone [11, 12]. If the PO antibiotic selected has similar pharmacokinetics, i.e., serum half life (t1/2), blood and tissue levels, etc., as its IV equivalent, there are few reasons to use IV therapy instead of PO therapy. Certainly, critically ill patients may benefit from initial IV therapy until clinical improvement [11, 12]. However, most patients, even those who are critically ill, have been effectively treated by the oral route [13–15]. Clearly, those patients who are unable to absorb oral antibiotics necessarily must be treated IV [16, 17]. While OPAT is less costly than inpatient IV therapy, IV to PO switch therapy or oral therapy alone are more economical ways to treat patients without sacrificing clinical efficacy [5, 7]. While some antibiotics are not available in the United States and/or reflect differences in antimicrobial prescribing on both sides of the Atlantic, there are important cost implications in how antibiotic therapy is administered [17] (Table 1). Whether MRSA SSTIs are treated with monotherapy or multiple drugs, economically, it matters whether antibiotics are administered IV or orally [13, 10, 18]. In the hospital setting, many patients with SSTIs and most patients with SSTIs in the outpatient setting may be treated effectively entirely via the oral route [5, 12]. Over the past several decades, I have used minocycline extensively for the treatment of MRSA infections. Minocycline has several advantages and a good safety profile, and is effective against hospital-acquired MRSA (HA-MRSA), community-onset MRSA (CO-MRSA), and community-acquired MRSA (CAMRSA) strains [16, 17]. Other oral MRSA antibiotics, e.g., clindamycin, trimethoprim–sulfamethoxazole (TMP-SMX), or doxycycline, are only variably clinically effective against CA-MRSA and lack efficacy against HA-MRSA and COMRSA, even if they are reported to be susceptible to MRSA in vitro [19–22]. Doxycycline, in particular, is often unable to eradicate CA-MRSA [22], perhaps because doxycycline induces its own resistance with MRSA [19]. MRSA SSTIs
Eur J Clin Microbiol Infect Dis Table 1 Treatment cost of anti-MRSA antibiotics IV MRSA antibioticsa
Usual adult dose
Cost per dose
IV admin. cost ($10/dose)
Drug cost per day
Total cost per day
Vancomycin Daptomycin Quinupristin/dalfopristin Telavancin Linezolid Tigecycline Minocycline Ceftaroline Rifampicin
1 g (IV) q12h=1 g 4 mg/kg/q24h=350 mg 7.5 mg/kg/q8h=525 mg 10 mg/kg/q24h=750 mg 600 mg (IV) q12h=600 mg 100 mg (IV) q24hb =100 mg 100 mg (IV) q12h=100 mg 600 mg (IV) q12h=600 mg 600 mg (IV) q24h=600 mg
$2.53 $336.23 $226.73 $285.87 $112.74 $164.52 $56.71 $54.96 $170.72
$20 $10 $30 $10 $20 $20 $20 $20 $10
$5.06+$20=$25.06 $336.23+$10=$346.23 $680.19+$30=$710.19 $285.87+$10=$295.87 $132.74+$20=$152.74 $164.52+$10=$174.52 $113.42+$20=$133.42 $109.92+$20=$129.92 $170.72+$10=$180.72
Drug cost + RFTs Drug cost + RFTs Drug cost + CPK Drug cost + RFTs Drug cost + CBCs NA NA NA Drug cost + LFTs
PO MRSA antibiotics
Usual adult dose (70 kg)
Cost per dose
IV admin. cost ($10/dose)
Drug cost per day
Total cost per day
600 mg (PO) q12h 300 mg (PO) q6h 1 DS tablet (PO) q6h 100 mg (PO) q12h 100 mg (PO) q12h
$102.90 $0.19 $0.60 $3.00 $0.20
$0 $0 $0 $0 $0
$205.80 $0.76 $2.40 $6.00 $0.40
Drug cost + CBCs Drug cost + CD Drug cost + RFTs
Linezolid Clindamycinc TMP-SMXc Doxycyclinec Minocycline
RFTs renal function tests, LFTs liver function tests, CBCs complete blood counts, CPK creatine phosphokinase, CD if C. difficile diarrhea/colitis, cost of stool tests for C. difficile, NA not applicable a
Assumes patients ill enough to require hospital admission
b
Plus 200 mg (IV) ×1 (loading dose)=$329.04, then 100 mg (IV) q24h (maintenance dose)
c
CA-MRSA strains may be susceptible in vitro, but not reliably effective in vivo. Also, clindamycin, TMP-SMX, and doxycycline less or not effective against HA-MRSA and CO-MRSA strains; 1 DS tablet: TMP=160 mg, SMX=400 mg
treated with doxycycline often fail to resolve after days or weeks of therapy, but rapidly resolve on minocycline therapy [21, 22]. While minocycline is not used extensively in the United States, in our 600-bed university affiliated teaching hospital, I have perhaps the most extensive experience in treating serious systemic infections as well as MRSA SSTIs with minocycline IV as part of an IV to PO switch regimen or entirely via the oral route. In patients that would be getting IV therapy in the hospital or OPAT, the clinical and economic advantages of oral therapy are considerable [23, 24]. There are powerful pharmacoeconomic reasons in using oral minocycline for the treatment of MRSA SSTIs [10–12, 21, 22] (Table 2). The economic advantages of IV to PO switch therapy are in terms of lower antibiotic costs and decreasing hospital LOS [1, 6, 7]. The other important clinical benefits of oral antibiotic therapy is the absence of IV-related complications, e.g., phlebitis, line infections (bacteremias, candidemias), endocarditis, etc. Shorter LOS also decreases the potential for other nosocomial infections. Earlier discharge on oral antibiotics decreases the potential for IV antibiotic side effects and drug–drug interactions [11–14]. Since the bioavailability of oral antibiotics used for oral therapy is essentially the same as when given via the IV route, there is no advantage in using IV therapy in many serious systemic infections [12, 15]. For oral antibiotic therapy, physicians should select an antibiotic with an
appropriate spectrum with proven clinical efficacy, optimal pharmacokinetics, and with a bioavailability of >90 % [16, 17]. In these situations, PO antibiotic therapy is not only equivalent to IV therapy, but has many clinical and economic advantages in terms of reducing healthcare costs, vis-à-vis fewer complications, and decreased LOS [15, 25]. Dr. Seaton and Table 2 Antibiotic therapy (IV vs. IV → PO switch vs. PO) of MRSA SSTIsa Total cost Total therapy IV/PO×10 D total IV therapy×10 D Vancomycin 1 g (IV) q12h: C/D: $25.06×10 D=$225.60 (cost/day) IV→PO (IV×3 D → PO×7 D switch)=10 D total Vancomycin 1 g (IV) q12h: C/D=$25.06×3 D=$75.18 plus Minocycline 100 mg (PO) q12h: C/D=$0.40×7 D=$2.80 Oral therapy×10 D total Minocycline 100 mg (PO) q12h: C/D=$0.40×10 D=$4.00 Usual duration of therapy=10 D; C/D cost/day a
Incision and drainage (I & D)
$225.60
$75.18 plus $2.80 Total: $77.98
$4.00
Eur J Clin Microbiol Infect Dis
colleagues are to be commended in reporting the economic benefits of IV to PO therapy and I enthusiastically support their conclusions [1]. However, even more cost-effective than IV to PO switch therapy is treatment entirely by oral antibiotic therapy [12, 15]. Based on my extensive experience, may I suggest that minocycline is an underappreciated and underutilized inexpensive and effective MRSA antibiotic. For the therapy of MRSA SSTIs, minocycline is reliably effective and the least expensive MRSA oral antibiotic.
References 1. Seaton RA, Johal S, Coia JE et al (2014) Economic evaluation of treatment for MRSA complicated skin and soft tissue infections in Glasgow hospitals. Eur J Clin Microbiol Infect Dis 33:305–311 2. Gould FK, Brindle R, Chadwick PR et al (2009) Guidelines (2008) for the prophylaxis and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in the United Kingdom. J Antimicrob Chemother 63:849–861 3. Dryden M, Andrasevic AT, Bassetti M et al (2010) A European survey of antibiotic management of methicillin-resistant Staphylococcus aureus infection: current clinical opinion and practice. Clin Microbiol Infect 16(Suppl 1):3–30 4. Seaton RA, Sharp E, Bezlyak V et al (2011) Factors associated with outcome and duration of therapy in outpatient parenteral antibiotic therapy (OPAT) patients with skin and soft-tissue infections. Int J Antimicrob Agents 38:243–248 5. Chapman ALN, Seaton RA, Cooper MA et al (2012) Good practice recommendations for outpatient parenteral antimicrobial therapy (OPAT) in adults in the UK: a consensus statement. J Antimicrob Chemother 67:1053–1062 6. Cunha BA (2001) Oral or intravenous-to-oral antibiotic switch therapy for treating patients with community-acquired pneumonia. Am J Med 111:412–413 7. Cunha BA (2004) Empiric oral monotherapy for hospitalized patients with community-acquired pneumonia: an idea whose time has come. Eur J Clin Microbiol Infect Dis 23:78–81 8. Cunha BA (2005) Methicillin-resistant Staphylococcus aureus: clinical manifestations and antimicrobial therapy. Clin Microbiol Infect 11:33–42 9. Cunha BA (2014) Cephalexin remains the preferred antibiotic for uncomplicated cellulitis: revisited. J Chemother 26:65–66
10. Cunha BA (1998) Factors in antibiotic selection for hospital formularies (part I). Hosp Formul 33:558–572 11. Cunha BA (2008) Oral and i.v.-to-p.o. switch antibiotic therapy of hospitalized patients with serious infections. Scand J Infect Dis 40: 1004–1006 12. Cunha BA (2006) Oral antibiotic therapy of serious systemic infections. Med Clin North Am 90:1197–1222 13. Rubinstein E, Keynan Y (2013) Short-course therapy for severe infections. Int J Antimicrob Agents 42:S22–S24 14. Lidji M, Rubinstein E, Samra H (1978) Bacterial endocarditis on a prosthetic valve. Oral treatment with amoxicillin. Chest 74:224–225 15. Cunha BA (2005) Oral antibiotic treatment of MRSA infections. J Hosp Infect 60:88–90 16. Cunha BA (ed) (2013) Antibiotic essentials, 12th edn. Jones and Bartlett, Sudbury, pp 8–16, 132–135, 595–597, 647–648, 680–682 17. Kucers A, Crowe SM, Grayson ML et al (eds) (1997) Kucers’ the use of antibiotics, 4th edn. Butterworth-Heinemann, Oxford, pp 719–763 18. McKinnon PS, Sorensen SV, Liu LZ, Itani KM (2006) Impact of linezolid on economic outcomes and determinants of cost in a clinical trial evaluating patients with MRSA complicated skin and soft-tissue infections. Ann Pharmacother 40:1017–1023 19. Schwartz BS, Graber CJ, Diep BA et al (2009) Doxycycline, not minocycline, induces its own resistance in multidrug-resistant, community-associated methicillin-resistant Staphylococcus aureus clone USA300. Clin Infect Dis 48:1483–1484 20. Cunha BA (1997) Problems arising in antimicrobial therapy due to false susceptibility testing. J Chemother 9:25–35 21. Cunha BA (2010) Minocycline versus doxycycline for meticillinresistant Staphylococcus aureus (MRSA): in vitro susceptibility versus in vivo effectiveness. Int J Antimicrob Agents 35:517–518 22. Cunha BA (2013) Minocycline, often forgotten but preferred to trimethoprim–sulfamethoxazole or doxycycline for the treatment of community-acquired meticillin-resistant Staphylococcus aureus skin and soft-tissue infections. Int J Antimicrob Agents 42:497–499 23. Gray A, Dryden M, Charos A (2012) Antibiotic management and early discharge from hospital: an economic analysis. J Antimicrob Chemother 67:2297–2302 24. Dryden M, Saeed K, Townsend R et al (2012) Antibiotic stewardship and early discharge from hospital: impact of a structured approach to antimicrobial management. J Antimicrob Chemother 67:2289–2296 25. Cunha BA (2014) Minocycline is a reliable and effective oral option to treat meticillin-resistant Staphylococcus aureus skin and soft-tissue infections, including doxycycline treatment failures. Int J Antimicrob Agents 43:386–387
LETTER TO THE EDITOR
Pharmacoeconomic advantages of oral minocycline for the therapy of methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections (SSTIs) B. A. Cunha
Received: 2 April 2014 / Accepted: 7 April 2014 # Springer-Verlag Berlin Heidelberg 2014
Dear Editor, I read with great interest the article by Dr. Seaton et al. regarding the economic aspects of methicillin-resistant Staphylococcus aureus (MRSA) therapy for complicated skin and soft tissue infections (SSTIs) [1]. Their interesting and well executed paper merits additional comments and a North American perspective. The authors’ article on MRSA SSTIs discussed the costs of intravenous (IV) antibiotic regimens and the cost savings of early in-house discharge using IV to oral (PO) switch therapy and outpatient parenteral antibiotic therapy (OPAT) using linezolid, rifampicin, or doxycycline [2–7]. MRSA SSTIs mainly present as cutaneous abscesses, in contrast to group A SSTIs, that present as cellulitis [8, 9]. The cornerstone of therapy for MRSA SSTI cutaneous abscesses is incision and drainage. Antimicrobial therapy is adjunctive to prevent bacteremia and further extension of the MRSA SSTI [8]. The cost of IV antibiotics is usually substantially higher than the equivalent PO dose [1–3]. On the basis of drug acquisition costs alone, it is obvious that IV to PO switch therapy is much less expensive than IV therapy to the healthcare system [6, 7, 10]. Not only are antibiotic costs less in IV to PO switch programs, but the patients’ length of stay (LOS) is also decreased with earlier discharge on PO therapy [11]. Non-critically ill patients with serious systemic infections may also be effectively managed with oral antibiotic therapy alone [12–15]. Physicians lacking IV to PO switch experience are often reluctant to treat hospitalized patients B. A. Cunha (*) Infectious Disease Division, Winthrop-University Hospital, 222 Station Plaza North (Suite #432), Mineola, NY 11501, USA e-mail: [email protected] B. A. Cunha School of Medicine, State University of New York, Stony Brook, NY, USA
using PO antibiotics alone [11, 12]. If the PO antibiotic selected has similar pharmacokinetics, i.e., serum half life (t1/2), blood and tissue levels, etc., as its IV equivalent, there are few reasons to use IV therapy instead of PO therapy. Certainly, critically ill patients may benefit from initial IV therapy until clinical improvement [11, 12]. However, most patients, even those who are critically ill, have been effectively treated by the oral route [13–15]. Clearly, those patients who are unable to absorb oral antibiotics necessarily must be treated IV [16, 17]. While OPAT is less costly than inpatient IV therapy, IV to PO switch therapy or oral therapy alone are more economical ways to treat patients without sacrificing clinical efficacy [5, 7]. While some antibiotics are not available in the United States and/or reflect differences in antimicrobial prescribing on both sides of the Atlantic, there are important cost implications in how antibiotic therapy is administered [17] (Table 1). Whether MRSA SSTIs are treated with monotherapy or multiple drugs, economically, it matters whether antibiotics are administered IV or orally [13, 10, 18]. In the hospital setting, many patients with SSTIs and most patients with SSTIs in the outpatient setting may be treated effectively entirely via the oral route [5, 12]. Over the past several decades, I have used minocycline extensively for the treatment of MRSA infections. Minocycline has several advantages and a good safety profile, and is effective against hospital-acquired MRSA (HA-MRSA), community-onset MRSA (CO-MRSA), and community-acquired MRSA (CAMRSA) strains [16, 17]. Other oral MRSA antibiotics, e.g., clindamycin, trimethoprim–sulfamethoxazole (TMP-SMX), or doxycycline, are only variably clinically effective against CA-MRSA and lack efficacy against HA-MRSA and COMRSA, even if they are reported to be susceptible to MRSA in vitro [19–22]. Doxycycline, in particular, is often unable to eradicate CA-MRSA [22], perhaps because doxycycline induces its own resistance with MRSA [19]. MRSA SSTIs
Eur J Clin Microbiol Infect Dis Table 1 Treatment cost of anti-MRSA antibiotics IV MRSA antibioticsa
Usual adult dose
Cost per dose
IV admin. cost ($10/dose)
Drug cost per day
Total cost per day
Vancomycin Daptomycin Quinupristin/dalfopristin Telavancin Linezolid Tigecycline Minocycline Ceftaroline Rifampicin
1 g (IV) q12h=1 g 4 mg/kg/q24h=350 mg 7.5 mg/kg/q8h=525 mg 10 mg/kg/q24h=750 mg 600 mg (IV) q12h=600 mg 100 mg (IV) q24hb =100 mg 100 mg (IV) q12h=100 mg 600 mg (IV) q12h=600 mg 600 mg (IV) q24h=600 mg
$2.53 $336.23 $226.73 $285.87 $112.74 $164.52 $56.71 $54.96 $170.72
$20 $10 $30 $10 $20 $20 $20 $20 $10
$5.06+$20=$25.06 $336.23+$10=$346.23 $680.19+$30=$710.19 $285.87+$10=$295.87 $132.74+$20=$152.74 $164.52+$10=$174.52 $113.42+$20=$133.42 $109.92+$20=$129.92 $170.72+$10=$180.72
Drug cost + RFTs Drug cost + RFTs Drug cost + CPK Drug cost + RFTs Drug cost + CBCs NA NA NA Drug cost + LFTs
PO MRSA antibiotics
Usual adult dose (70 kg)
Cost per dose
IV admin. cost ($10/dose)
Drug cost per day
Total cost per day
600 mg (PO) q12h 300 mg (PO) q6h 1 DS tablet (PO) q6h 100 mg (PO) q12h 100 mg (PO) q12h
$102.90 $0.19 $0.60 $3.00 $0.20
$0 $0 $0 $0 $0
$205.80 $0.76 $2.40 $6.00 $0.40
Drug cost + CBCs Drug cost + CD Drug cost + RFTs
Linezolid Clindamycinc TMP-SMXc Doxycyclinec Minocycline
RFTs renal function tests, LFTs liver function tests, CBCs complete blood counts, CPK creatine phosphokinase, CD if C. difficile diarrhea/colitis, cost of stool tests for C. difficile, NA not applicable a
Assumes patients ill enough to require hospital admission
b
Plus 200 mg (IV) ×1 (loading dose)=$329.04, then 100 mg (IV) q24h (maintenance dose)
c
CA-MRSA strains may be susceptible in vitro, but not reliably effective in vivo. Also, clindamycin, TMP-SMX, and doxycycline less or not effective against HA-MRSA and CO-MRSA strains; 1 DS tablet: TMP=160 mg, SMX=400 mg
treated with doxycycline often fail to resolve after days or weeks of therapy, but rapidly resolve on minocycline therapy [21, 22]. While minocycline is not used extensively in the United States, in our 600-bed university affiliated teaching hospital, I have perhaps the most extensive experience in treating serious systemic infections as well as MRSA SSTIs with minocycline IV as part of an IV to PO switch regimen or entirely via the oral route. In patients that would be getting IV therapy in the hospital or OPAT, the clinical and economic advantages of oral therapy are considerable [23, 24]. There are powerful pharmacoeconomic reasons in using oral minocycline for the treatment of MRSA SSTIs [10–12, 21, 22] (Table 2). The economic advantages of IV to PO switch therapy are in terms of lower antibiotic costs and decreasing hospital LOS [1, 6, 7]. The other important clinical benefits of oral antibiotic therapy is the absence of IV-related complications, e.g., phlebitis, line infections (bacteremias, candidemias), endocarditis, etc. Shorter LOS also decreases the potential for other nosocomial infections. Earlier discharge on oral antibiotics decreases the potential for IV antibiotic side effects and drug–drug interactions [11–14]. Since the bioavailability of oral antibiotics used for oral therapy is essentially the same as when given via the IV route, there is no advantage in using IV therapy in many serious systemic infections [12, 15]. For oral antibiotic therapy, physicians should select an antibiotic with an
appropriate spectrum with proven clinical efficacy, optimal pharmacokinetics, and with a bioavailability of >90 % [16, 17]. In these situations, PO antibiotic therapy is not only equivalent to IV therapy, but has many clinical and economic advantages in terms of reducing healthcare costs, vis-à-vis fewer complications, and decreased LOS [15, 25]. Dr. Seaton and Table 2 Antibiotic therapy (IV vs. IV → PO switch vs. PO) of MRSA SSTIsa Total cost Total therapy IV/PO×10 D total IV therapy×10 D Vancomycin 1 g (IV) q12h: C/D: $25.06×10 D=$225.60 (cost/day) IV→PO (IV×3 D → PO×7 D switch)=10 D total Vancomycin 1 g (IV) q12h: C/D=$25.06×3 D=$75.18 plus Minocycline 100 mg (PO) q12h: C/D=$0.40×7 D=$2.80 Oral therapy×10 D total Minocycline 100 mg (PO) q12h: C/D=$0.40×10 D=$4.00 Usual duration of therapy=10 D; C/D cost/day a
Incision and drainage (I & D)
$225.60
$75.18 plus $2.80 Total: $77.98
$4.00
Eur J Clin Microbiol Infect Dis
colleagues are to be commended in reporting the economic benefits of IV to PO therapy and I enthusiastically support their conclusions [1]. However, even more cost-effective than IV to PO switch therapy is treatment entirely by oral antibiotic therapy [12, 15]. Based on my extensive experience, may I suggest that minocycline is an underappreciated and underutilized inexpensive and effective MRSA antibiotic. For the therapy of MRSA SSTIs, minocycline is reliably effective and the least expensive MRSA oral antibiotic.
References 1. Seaton RA, Johal S, Coia JE et al (2014) Economic evaluation of treatment for MRSA complicated skin and soft tissue infections in Glasgow hospitals. Eur J Clin Microbiol Infect Dis 33:305–311 2. Gould FK, Brindle R, Chadwick PR et al (2009) Guidelines (2008) for the prophylaxis and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in the United Kingdom. J Antimicrob Chemother 63:849–861 3. Dryden M, Andrasevic AT, Bassetti M et al (2010) A European survey of antibiotic management of methicillin-resistant Staphylococcus aureus infection: current clinical opinion and practice. Clin Microbiol Infect 16(Suppl 1):3–30 4. Seaton RA, Sharp E, Bezlyak V et al (2011) Factors associated with outcome and duration of therapy in outpatient parenteral antibiotic therapy (OPAT) patients with skin and soft-tissue infections. Int J Antimicrob Agents 38:243–248 5. Chapman ALN, Seaton RA, Cooper MA et al (2012) Good practice recommendations for outpatient parenteral antimicrobial therapy (OPAT) in adults in the UK: a consensus statement. J Antimicrob Chemother 67:1053–1062 6. Cunha BA (2001) Oral or intravenous-to-oral antibiotic switch therapy for treating patients with community-acquired pneumonia. Am J Med 111:412–413 7. Cunha BA (2004) Empiric oral monotherapy for hospitalized patients with community-acquired pneumonia: an idea whose time has come. Eur J Clin Microbiol Infect Dis 23:78–81 8. Cunha BA (2005) Methicillin-resistant Staphylococcus aureus: clinical manifestations and antimicrobial therapy. Clin Microbiol Infect 11:33–42 9. Cunha BA (2014) Cephalexin remains the preferred antibiotic for uncomplicated cellulitis: revisited. J Chemother 26:65–66
10. Cunha BA (1998) Factors in antibiotic selection for hospital formularies (part I). Hosp Formul 33:558–572 11. Cunha BA (2008) Oral and i.v.-to-p.o. switch antibiotic therapy of hospitalized patients with serious infections. Scand J Infect Dis 40: 1004–1006 12. Cunha BA (2006) Oral antibiotic therapy of serious systemic infections. Med Clin North Am 90:1197–1222 13. Rubinstein E, Keynan Y (2013) Short-course therapy for severe infections. Int J Antimicrob Agents 42:S22–S24 14. Lidji M, Rubinstein E, Samra H (1978) Bacterial endocarditis on a prosthetic valve. Oral treatment with amoxicillin. Chest 74:224–225 15. Cunha BA (2005) Oral antibiotic treatment of MRSA infections. J Hosp Infect 60:88–90 16. Cunha BA (ed) (2013) Antibiotic essentials, 12th edn. Jones and Bartlett, Sudbury, pp 8–16, 132–135, 595–597, 647–648, 680–682 17. Kucers A, Crowe SM, Grayson ML et al (eds) (1997) Kucers’ the use of antibiotics, 4th edn. Butterworth-Heinemann, Oxford, pp 719–763 18. McKinnon PS, Sorensen SV, Liu LZ, Itani KM (2006) Impact of linezolid on economic outcomes and determinants of cost in a clinical trial evaluating patients with MRSA complicated skin and soft-tissue infections. Ann Pharmacother 40:1017–1023 19. Schwartz BS, Graber CJ, Diep BA et al (2009) Doxycycline, not minocycline, induces its own resistance in multidrug-resistant, community-associated methicillin-resistant Staphylococcus aureus clone USA300. Clin Infect Dis 48:1483–1484 20. Cunha BA (1997) Problems arising in antimicrobial therapy due to false susceptibility testing. J Chemother 9:25–35 21. Cunha BA (2010) Minocycline versus doxycycline for meticillinresistant Staphylococcus aureus (MRSA): in vitro susceptibility versus in vivo effectiveness. Int J Antimicrob Agents 35:517–518 22. Cunha BA (2013) Minocycline, often forgotten but preferred to trimethoprim–sulfamethoxazole or doxycycline for the treatment of community-acquired meticillin-resistant Staphylococcus aureus skin and soft-tissue infections. Int J Antimicrob Agents 42:497–499 23. Gray A, Dryden M, Charos A (2012) Antibiotic management and early discharge from hospital: an economic analysis. J Antimicrob Chemother 67:2297–2302 24. Dryden M, Saeed K, Townsend R et al (2012) Antibiotic stewardship and early discharge from hospital: impact of a structured approach to antimicrobial management. J Antimicrob Chemother 67:2289–2296 25. Cunha BA (2014) Minocycline is a reliable and effective oral option to treat meticillin-resistant Staphylococcus aureus skin and soft-tissue infections, including doxycycline treatment failures. Int J Antimicrob Agents 43:386–387
