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Review
. 2024 May 19;16(10):1934.
doi: 10.3390/cancers16101934.

Systematic Review of Beta-Lactam vs. Beta-Lactam plus Aminoglycoside Combination Therapy in Neutropenic Cancer Patients

Kazuhiro Ishikawa  1 , Tomoaki Nakamura  2 , Fujimi Kawai  3 , Erika Ota  4   5 , Nobuyoshi Mori  1
Affiliations
Review

Systematic Review of Beta-Lactam vs. Beta-Lactam plus Aminoglycoside Combination Therapy in Neutropenic Cancer Patients

Kazuhiro Ishikawa et al. Cancers (Basel). .

Erratum in

Abstract

We performed a systematic review of studies that compared beta-lactams vs. beta-lactams plus aminoglycosides for the treatment of febrile neutropenia in cancer patients.

Method: We searched CENTRAL, MEDLINE, and Embase for studies published up to October 2023, and randomized controlled trials (RCTs) that compared anti-Pseudomonas aeruginosa beta-lactam monotherapy with any combination of an anti-Pseudomonas aeruginosa beta-lactam and an aminoglycoside were included.

Result: The all-cause mortality rate of combination therapy showed no significant differences compared with that of monotherapy (RR 0.99, 95% CI 0.84 to 1.16, high certainty of evidence). Infection-related mortality rates showed that combination therapy had a small positive impact compared with the intervention with monotherapy (RR 0.83, 95% CI 0.66 to 1.05, high certainty of evidence). Regarding treatment failure, combination therapy showed no significant differences compared with monotherapy (RR 0.99, 95% CI 0.94 to 1.03, moderate certainty of evidence). In the sensitivity analysis, the treatment failure data published between 2010 and 2019 showed better outcomes in the same beta-lactam group (RR 1.10 [95% CI, 1.01-1.19]). Renal failure was more frequent with combination therapy of any daily dosing regimen (RR 0.46, 95% CI 0.36 to 0.60, high certainty of evidence).

Conclusion: We found combining aminoglycosides with a narrow-spectrum beta-lactam did not spare the use of broad-spectrum antibiotics. Few studies included antibiotic-resistant bacteria and a detailed investigation of aminoglycoside serum levels, and studies that combined the same beta-lactams showed only a minimal impact with the combination therapy. In the future, studies that include the profile of antibiotic-resistant bacteria and the monitoring of serum aminoglycoside levels will be required.

Keywords: beta-lactam plus aminoglycoside; cancer patient; combination therapy; febrile neutropenia.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Identification process for eligible studies.
Figure 2
Figure 2
Risk of bias graph [13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76].
Figure 3
Figure 3
(a) Comparison of all-cause mortality between monotherapy and AG combination therapy in same beta-lactam. Abbreviations: CI; confidence interval, AG; aminoglycoside. (b) Comparison of all-cause mortality between monotherapy and AG combination therapy in different beta-lactam. Abbreviations: CI; confidence interval, AG; aminoglycoside. (c) Comparison of all-cause mortality between monotherapy and AG combination therapy in all beta-lactam. Abbreviations: CI; confidence interval, AG; aminoglycoside [13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76].
Figure 4
Figure 4
(a) Comparison of infection-related mortality between monotherapy and AG combination therapy in same beta-lactam. Abbreviations: CI; confidence interval, AG; aminoglycoside. (b) Comparison of infection-related between monotherapy and AG combination therapy in different beta-lactam. Abbreviations: CI; confidence interval, AG; aminoglycoside. (c) Comparison of infection-related between monotherapy and AG combination therapy in all beta-lactam. Abbreviations: CI; confidence interval, AG; aminoglycoside [13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76].
Figure 4
Figure 4
(a) Comparison of infection-related mortality between monotherapy and AG combination therapy in same beta-lactam. Abbreviations: CI; confidence interval, AG; aminoglycoside. (b) Comparison of infection-related between monotherapy and AG combination therapy in different beta-lactam. Abbreviations: CI; confidence interval, AG; aminoglycoside. (c) Comparison of infection-related between monotherapy and AG combination therapy in all beta-lactam. Abbreviations: CI; confidence interval, AG; aminoglycoside [13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76].
Figure 5
Figure 5
(a) Comparison of treatment failure between monotherapy and AG combination therapy in same beta-lactam. Abbreviations: CI; confidence interval, AG; aminoglycoside. (b) Comparison of treatment failure between monotherapy and AG combination therapy in different beta-lactam. Abbreviations: CI; confidence interval, AG; aminoglycoside. (c) Comparison of treatment failure between monotherapy and AG combination therapy in all beta-lactam. Abbreviations: CI; confidence interval, AG; aminoglycoside [13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76].
Figure 5
Figure 5
(a) Comparison of treatment failure between monotherapy and AG combination therapy in same beta-lactam. Abbreviations: CI; confidence interval, AG; aminoglycoside. (b) Comparison of treatment failure between monotherapy and AG combination therapy in different beta-lactam. Abbreviations: CI; confidence interval, AG; aminoglycoside. (c) Comparison of treatment failure between monotherapy and AG combination therapy in all beta-lactam. Abbreviations: CI; confidence interval, AG; aminoglycoside [13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76].
Figure 6
Figure 6
(a) Comparison of nephrotoxicity between monotherapy and AG combination therapy in the once daily regimen. Abbreviations: CI; confidence interval, AG; aminoglycoside. (b) Comparison of nephrotoxicity between monotherapy versus AG combination therapy in the multiple daily dosing regimen. Abbreviations: CI; confidence interval, AG; aminoglycoside. (c) Comparison of nephrotoxicity between monotherapy and AG combination therapy in any daily regimen. Abbreviations: CI; confidence interval, AG; aminoglycoside [13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76].
Figure 6
Figure 6
(a) Comparison of nephrotoxicity between monotherapy and AG combination therapy in the once daily regimen. Abbreviations: CI; confidence interval, AG; aminoglycoside. (b) Comparison of nephrotoxicity between monotherapy versus AG combination therapy in the multiple daily dosing regimen. Abbreviations: CI; confidence interval, AG; aminoglycoside. (c) Comparison of nephrotoxicity between monotherapy and AG combination therapy in any daily regimen. Abbreviations: CI; confidence interval, AG; aminoglycoside [13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76].
Figure 7
Figure 7
Ambler classification.
See this image and copyright information in PMC

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