Cochrane meta-analysis: teicoplanin versus vancomycin for proven or suspected infection

Bugano, Diogo Diniz Gomes; Cavalcanti, Alexandre Biasi; Goncalves, Anderson Roman; Almeida, Claudia Salvini de; Silva, Eliézer

doi:10.1590/S1679-45082011AO2020

Diogo Diniz Gomes Bugano

Hospital das Clínicas, Universidade de São Paulo – USP, São Paulo (SP), Brazil

Alexandre Biasi Cavalcanti Corresponding author: Education and Research Institute of Hospital do Coração – HCor – Alexandre Biasi Cavalcanti – Rua Abílio Soares, 250, 12° andar – Paraíso – CEP 04005-909 – São Paulo (SP), Brasil – E-mail: alexbiasi@einstein.br

Education and Research Institute of Hospital do Coração – HCor, São Paulo (SP), Brazil

Anderson Roman Goncalves

Medical department, Universidade da Região de Joinville – UNIVILLE -Joinville (SC), Brazil

Claudia Salvini de Almeida

Department of Pediatrics, Hospital das Clinicas da Universidade de São Paulo - USP - São Paulo (SP), Brazil

Eliézer Silva

Intensive Care Unit, Hospital Israelita Albert Einstein – HIAE, São Paulo (SP), Brazil

Corresponding author: Education and Research Institute of Hospital do Coração – HCor – Alexandre Biasi Cavalcanti – Rua Abílio Soares, 250, 12° andar – Paraíso – CEP 04005-909 – São Paulo (SP), Brasil – E-mail: alexbiasi@einstein.br

Conflict of interest: none

Study	n	Age group	Patients	Exclusion if previous kidney injury	Definition of previous kidney injury	Teicoplanin dose	Vancomycin dose	Definition of nephrotoxicity
Auperh, 1997	67	Chidren	Solid neoplasm + febrife neutropenia	Yes	Severe CKD	10 mg/kg BID for 3 doses, than OD	10 mg/kg every 6hs	Moderate renal faibre
Charboneau, 1994	56	Adults	Severe Gram-positive infections	Yes	Cr > 2.3 mg/dL	6 mg/kg BID for 3 doses, than OD	24 mg/kg/day in 3 or 4 doses	Increase in serum Cr >0.5 mg/dL
Choi, 1992	44	>15 years	Hematological malignancies + febrile neutropenia	Yes	Cr > 1.5 mg/dL or CrCl < 60 mL/min OD	400mg BID for 2 doses, than OD	500 mg every 8hs	NS
Chow, 1993	53	Adults	Hickman catheter + febrile neutropenia	Yes	Cr > 2.5 mg/dL	6 mg/kg BID for 3 doses, than OD	14 mg/kg BID	Cr > 1.24 mg/dL
Cony-Makhoul, 1990	65	Adults	Hematologic malignancies + febrile neutropenia	No	NA	6 mg/kg BID for 3 doses, than OD	15 mg/kg BID	NS
Pham Dang, 2001	30	Adults	Joint or bone infection	No	HA	400 mg BID for 3 doses, than OD, IM	Continuous infusion to obtain serum levels between 20-30 mg/L	Increase in serum Cr or anuria
D’Antonio, 2004	154	Adults	Hematologic malignancies + febrile neutropenia	Yes	Cr > 3.0 mg/dL	6 mg/kg BID for 2 days, than OD	15 mg/kg BID	reversible renal toxicity
Figuera, 1996	149	Adults	Hematologic malignancies or BMT + febrile neutropenia	Yes	Cr > 2.5 mg/dL	400mg BID for 3 doses, than OD	lg BID	Cr > 1.5 mg/dL
Fortun, 2001	23	Adults	MRSA right-side endocarditis	Yes	Cr > 2.5 mg/dL	24mg/kg OD in the 1st day, than 12 mg/kg OD	500 mg every 6hs	Moderate increase in SCr
Hedström, 1995	80	Adults	Suspected or proven Gram-positive infection	Yes	CCr < 40 mL/min	400mg BID for 3 doses, than OD	lg BID	Increase in Cr
MMD-09-1992	242	Adults	Catheter-associated bloodstream infection	Unknown	NA	6 mg/kg BID for 3 doses, than OD	15 mg/kg BID	Rise of 0.5 mg/dL or more if baseline SCr< 3mg/dL or rise of 1 mg/dL if baseline Cr > 3 mg/dL.
MMD-14-1992	106	Adults	Vascular-access-associated bacteremia	Unknown	NA	3 schemes: A) 6 mg/kg BID for 3 doses, than OD; B) 6 mg/kg BID for 9 doses than 6-10 mg/kg OD;C) 10 mg/kg BID.	15 mg/kg BID	Rise of 0.5 mg/dL or more if baseline SCr< 3mg/dL or rise of 1 mg/dL if baseline Cr > 3 mg/dL.
MMD-19-1992	132	Adults	Bacteremia and endocarditis	Unknown	NA	2 schemess: A) For Staphylococcus aureus 30 mg/ kg BID for 3 doses, than OD; B) For Streptococcus sp 6mg/ kg OD	15 mg/kg BID	Rise of 0.5 mg/dL or more if baseline SCr< 3mg/dL or rise of 1 mg/dL if baseline Cr > 3 mg/dL.
Liu, 1996	45	Adults	MRSA bacteremia	Yes	Cr > 2.5mg/dL	400mg BID for 3 doses, than OD	500 mg every 6hs	Increase in Cr > 50%
Menichetti, 1994	635	Adults	Hematologic malignancies + febrile neutropenia	Yes	Cr > 1.4mg/dL	8 mg/kg loading dose, than 6mg/kg OD	15 mg/kg BID	Rise in Cr above normal range
Neville, 1995	56	Adults	Suspected or proven Gram-positive infection	Yes	Cr > 1.7mg/dL	400 mg OD (some patients 200 mg OD after 2nd day)	1g BID	Increase in Cr > 100%
Nucci, 1998	106	Adults	BMT + febrile neutropenia	No	NA	6 mg/kg BID for 3 doses, than OD	40 mg/kg/d in 1h infusion	Increase in Cr > 0.5 mg/dL or dcrease in CrCl > 50%
Rolston, 1994	64	Adults	Solid neoplasm with suspected or proven Gram-positive bacteremia	Yes	Cr >3.0mg/dL	6 mg/kg BID for 3 doses, than OD	15 mg/kg BID	Increase in Cr
Rolston, 1999	64	Adults	Catheter-associated infection with suspected or proven Gram-positive	Yes	Cr >3.0 mg/dL	6 mg/kg BID for 3 doses, than OD	15 mg/kg BID	Increase in Cr
Sidi, 2000	20	Children	Gram-positive bacteremia + febrile neutropenia	No	NA	10 mg/kg BID for 3 doses, than OD	40 mg/kg/d divided in 3 doses	Increase in Cr > 0.5 mp/dL
Smith, 1989	72	Adults	Hickman catheter-associated infection + hematological malignancies	No	NA	First 11 episodes 400 mg on day 1 than 200 mg OD; thereafter 800 mg on day 1 than 400 mg OD	1g BID	Increase in Cr > 0.5 mg/dL
Van der Auwera, 1991	74	Adults	Solid neoplasm + suspected of proven Gram-positive infection	Yes	Cr> 2.0 mg/dL	First 21 patients 400 mg OD first 3 days than 200 mgOD; thereafter 400mg BID 1st day than 400 mg OD	1g BID	Increase in Cr > 0.5 mg/dL
Van Laethem, 1988	21	Adults	MRSA infection	Yes	Cr> 2.0 mg/dL	400 mg OD	1g BID	NS
Vazquez, 1999	76	Adults	Hematological malignancies + febrile neutropenia	Yes	Cr >1.5mg/dL	400 mg BID for 3 doses, than OD	According to serum levels	NS

Outcomes	Illustrative comparative risk		Relative effect (95%CI)	Number of participants (studies)	Quality of evidence (GRADE)
	Presumed risk	Corresponding risk
	Control	Teicoplanin versus vancomycin
Nephrotoxicity	92 per 1,000	61 per 1,000 (44-83)	RR 0.66 (0.48-0.9)	2,596 (23 studies)	Moderate
Clinical cure or improvement	730 per 1,000	752 per 1,000 (715-788)	RR 1.03 (0.98-1.08)	1,703 (20 studies)	Moderate
Microbiological cure	850 per 1,000	833 per 1,000 (790-875)	RR 0.98 (0.93-1.03)	914 (16 studies)	Moderate
Renal failure needing dialysis	See comment	See comment	Not estimable	606 (3)	See comment
Mortality	103 per 1,000	105 per 1,000	RR 1.02 (0.79-1.3)	1,565 (16 studies)	Low
Skin rash	60 per 1,000	34 per 1,000 (21-55)	RR 0.57 (0.35-0.92)	1,823 (18 studies)	Moderate
Total adverse events	184 per 1,000	103 per 1,000	RR 0.56 (0.33-0.95)	880 (11 studies)	Very low

Database	Electronic search strategies
Central	MeSH descriptor Teicoplanin, this term only (teicoplanin):ti, ab, kw in Clinical Trials (teichomycin):ti, ab, kw in Clinical Trials (targocid):ti, ab, kw or (targosid): ti, ab, kw in Clinical Trials (1 OR 2 OR 3 OR 4) MeSH descriptor Vancomycin, this term only MeSH descriptor Vancomycin Resistance, this term only (vancomycin):ti, ab, kw in Clinical Trials (diatracin):ti, ab, kw in Clinical Trials (vancocin):ti, ab, kw in Clinical Trials (vancomicin):ti, ab, kw in Clinical Trials (vanco-cell* or vanco-saar):ti, ab, kw in Clinical Trials (lyphocin):ti, ab, kw in Clinical Trials (vancamycin):ti, ab, kw in Clinical Trials (vancoled):ti, ab, kw in Clinical Trials (vancococin*):ti, ab, kw in Clinical Trials (6 OR 7 OR 8 OR 9 OR 10 OR 11 OR 12 OR 13 OR 14 OR 15 OR 16) (5 AND 17)
MEDLINE	Teicoplanin/ teicoplanin$.tw. teichomycin.tw. targo?id.tw. or/1-4 Vancomycin/ Vancomycin Resistance/ vancomycin$.tw. diatracin$.tw. vancocin$.tw. vancomicin$.tw. (vanco-cell or vanco-saar).tw. lyphocin$.tw. vancamycin$.tw. vancoled$.tw. vanococin$.tw. or/6-16 and/5,17
EMBASE	Teicoplanin/ TEICOPLANIN DERIVATIVE/ teicoplanin$.tw. teichomycin$.tw. targo?id.tw. or/1-5 Vancomycin/ VANCOMYCIN DERIVATIVE/ vancomycin$.tw. diatracin$.tw. vancocin$.tw. vancomicin$.tw. (vanco-cell or vanco-saar).tw. lyphocin$.tw. vancamycin$.tw. vancoled$.tw. vanococin$.tw. or/7-17 and/6,18

Allocation concealment

–
Adequate (A): randomization method described it would not allow investigator/participant to know or influence intervention group before eligible participant entered in the study.
–
Unclear (B): randomization stated but no information on method used is available.
–
Inadequate (C): method of randomization used, such as alternate medical record numbers or unsealed envelopes; any information in the study that indicated that investigators or participants could influence intervention group.

Blinding

–
Blinding of investigators: yes/no/not stated/unclear or inadequate (if the study was described as double blind, but the method of blinding was not described or is not compatible with blinding).
–
Blinding of participants: yes/no/not stated/unclear or inadequate (if the study was described as double blind, but the method of blinding was not described or is not compatible with blinding).
–
Blinding of outcome assessors: yes/no/not stated/unclear or inadequate (if the study was described as double blind, but the method of blinding was not described or is not compatible with blinding).
–
Blinding of data analysis: yes/no/not stated/unclear or inadequate (if the study was described as double blind, but the method of blinding was not described or is not compatible with blinding). The above were considered not blinded if the treatment group can be identified in > 20% of participants because of the side effects of treatment.

Intention-to-treat

–
Yes: specifically reported by authors that intention
–
to
–
treat analysis was undertaken and this was confirmed on study assessment.
–
Yes: not stated but confirmed on study assessment.
–
No: not reported and lack of intention
–
to
–
treat analysis confirmed on study assessment (randomized patients were not included in the analysis because they did not receive the study intervention, they withdrew from the study or were not included because of protocol violation).
–
No: stated but not confirmed upon study assessment.
–
Not stated.

Completeness of follow-up

Proportions of participants excluded or lost to follow-up.

Study	Allocation concealment	Blinding			ITT analysis	Exclusion from analysis	Unit of analysis
Study	Allocation concealment	Investigators	Participants	Outcome assessors	ITT analysis	Exclusion from analysis	Unit of analysis
Auperin, 1997	Unclear	Unclear	Unclear	Unclear	Yes	3%	Patients
Charboneau, 1994	Unclear	No	No	Unclear	No	9%	Patients
Choi, 1992	Unclear	No	No	No	Yes	0%	Patients
Chow, 1993	Unclear	Yes	Yes	Unclear	No	6%	Patients
Cony-Makhoul, 1990	Unclear	No	No	Unclear	No	9%	Infection episode
Pham Dang, 2001	Adequate	No	No	Unclear	Yes	0%	Patients
D’Antonio, 2004	Unclear	Inadequate	Inadequate	Unclear	No	19%	Patients
Figuera, 1996	Unclear	No	No	Unclear	No	15%	Infection episode
Fortun, 2001	Unclear	No	No	No	No	13%	Patients
Hedström, 1995	Unclear	Inadequate	Unclear	Inadequate	No	40%	Patients
MMD-09-1992	Unclear	Yes	Yes	Yes	No	48%	Patients
MMD-14-1992	Unclear	Yes	Yes	Yes	No	51%	Patients
MMD-19-1992	Unclear	Yes	Yes	Yes	No	51%	Patients
Menichetti, 1994	Adequate	No	No	Yes	No	17%	Patients
Neville, 1995	Unclear	No	No	No	No	4%	Infection episode
Nucci, 1998	Unclear	No	Unclear	Unclear	No	15%	Patients
Rolston, 1994	Adequate	Yes	Yes	Yes	No	28%	Patients
Rolston, 1999	Adequate	Yes	Yes	Yes	No	48%	Patients
Sidi, 2000	Inadequate	No	No	Unclear	Yes	0%	Infection episode
Smith, 1989	Unclear	No	No	No	No	17%	Infection episode
Van der Auwera, 1991	Adequate	No	No	Unclear	Yes	4%	Patients
Van Laethem, 1988	Unclear	No	No	No	Yes	0%	Patients
Vazquez, 1999	Adequate	Unclear	Unclear	Unclear	Yes	0%	Patients

[1] Corresponding author: Education and Research Institute of Hospital do Coração – HCor – Alexandre Biasi Cavalcanti – Rua Abílio Soares, 250, 12° andar – Paraíso – CEP 04005-909 – São Paulo (SP), Brasil – E-mail: alexbiasi@einstein.br

Brasil

Brasil

Cochrane meta-analysis: teicoplanin versus vancomycin for proven or suspected infection

ABSTRACT

Objective:

Methods:

Results:

Limitations:

Conclusions: