The Efficacy of Using Combination Therapy against Multi-Drug and Extensively Drug-Resistant Pseudomonas aeruginosa in Clinical Settings
Abstract
:1. Introduction
2. Results and Discussion
Study No. | Treatment | Number of Patients Treated [n (%)] | Number of Patients with P. aeruginosa | Resistance | Microbiological Cure [n (%)] | Mortality [n (%)] | References | |
---|---|---|---|---|---|---|---|---|
Sensitive Strains [n (%)] | Resistant Strains [n (%)] | |||||||
8 | Colistin monotherapy | 12 (17.6) | 135 (52.3) ** | 123 (47.7) ** | MDR | - | 3 (25.0) * | [35] |
Colistin–meropenem | 28 (41.2) | - | 4 (14.3) * | |||||
Colistin–piperacillin–tazobactam | 10 (14.7) | - | 4 (40) * | |||||
Colistin–ampicillin–sulbactam | 1 (1.5) | - | 0 (0) * | |||||
Colistin with other agents I | 17 (25) | - | 6 (25.3) * | |||||
11 | β-lactam with aminoglycoside–fluoroquinolone | 28 (31.5) | 75 (77.3) 2 | 22 (23) 3 | XDR | - | 7 (25) | [38] |
Colistin with other agents | 7 (7.9) | - | 4 (57.1) | |||||
β-lactam with β-lactam | 2 (2.2) | - | 1 (50) | |||||
β-lactam | 26 | - | 10 (38.5) | |||||
Colistin | 8 | - | 3 (37.5) | |||||
Fluoroquinolone | 11 | - | 1 (9.1) | |||||
12 | Colistin | 4 (14.7) | 14 (44.8) | 18 (56.2) 1 | MDR/XDR | 6 (35.3) | - | [39] |
β-lactam | 15 (44.1) | - | ||||||
Colistin with β-lactam | 13 (38.2) | 11 (64.7) | - | |||||
Amikacin with β-lactam | 2 (5.9) | - |
3. Materials and Methods
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Mechanism of Resistance | Current Treatments | Emerging Treatments |
---|---|---|
β-lactamase production | Colistin | Ceftolozane–Tazobactam |
Porin loss/mutation | Colistin | Ceftazidime–Avibactam |
Efflux pump expression | Colistin | Aztreonam–Avibactam |
Fosfomycin | ||
Cefiderocol |
Study No. | Study Title | Study Design | Number of Patients | Clinical Indication | Age | Male Sex n (%) | References | ||
---|---|---|---|---|---|---|---|---|---|
Mean (SD) | Median (IQR) | ||||||||
1 | Epidemiology and outcome of infections with carbapenem-resistant Gram-negative bacteria treated with polymyxin B-based combination therapy | Single | OS | 104 | Various | 77 (±12.9) | - | 62 (59.6) | [28] |
2 | Polymyxin B in Combination with Antimicrobials Lacking In Vitro Activity versus Polymyxin B in Monotherapy in Critically Ill Patients with Acinetobacter baumannii or Pseudomonas aeruginosa Infections | Multi | RS | 101 | Various | 65.2 (±15.7) | - | 56 (55.4) | [29] |
3 | Impact of combination therapy and early de-escalation on outcome of ventilator-associated pneumonia caused by Pseudomonas aeruginosa | Single | RS | 100 | VAP | - | 64 (54–72) | 76 (76.0) | [30] |
4 | Active monotherapy and combination therapy for extensively drug-resistant Pseudomonas aeruginosa pneumonia | Single | RS | 136 | Various | - | 78 (70–83) | 74 (54) | [31] |
5 | Clinical characteristics and outcomes of Pseudomonas aeruginosa bacteremia in febrile neutropenic children and adolescents with the impact of antibiotic resistance: a retrospective study | Single | ROS | 31 | Febrile neutropenia | 9.5 (±5.4) | - | 26 (72.2) | [32] |
6 | Efficacy and safety of cefiderocol or best available therapy for the treatment of serious infections caused by carbapenem-resistant Gram-negative bacteria (CREDIBLE-CR): a randomised, open-label, multicentre, pathogen-focused, descriptive, phase 3 trial | Multi | RCT | 118 | Various | 63.0 (±16.7) | - | 101 (66.4) | [33] |
7 | Experience with Ceftolozane–Tazobactam for the Treatment of Serious Pseudomonas aeruginosa Infections in Saudi Tertiary Care Center | Single | ROS | 19 | Various | - | 57 (35–71) | 9 (47) | [34] |
8 | Colistin therapy for microbiologically documented multidrug-resistant Gram-negative bacterial infections: a retrospective cohort study of 258 patients | Single | RS | 258 | Various | 61.1 (±18.1) | - | 174 (67.4) | [35] |
9 | Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria: an open-label, randomised controlled trial | Multi | RCT | 406 | Various | 66 (±16) | - | 151 (37.2) | [36] |
10 | Intravenous polymyxin B for the treatment of nosocomial pneumonia caused by multidrug-resistant Pseudomonas aeruginosa | Single | OS | 74 | Nosocomial pneumonia | - | 55 (17–89) | 50 (67.6) | [37] |
11 | Characteristics, risk factors and outcomes of adult cancer patients with extensively drug-resistant Pseudomonas aeruginosa infections | Single | RS | 89 | Cancer | - | 73 (21–87) | 18 (81.8) | [38] |
12 | Osteoarticular infection caused by MDR Pseudomonas aeruginosa: the benefits of combination therapy with colistin plus β-lactams | Single | RS | 34 | Osteoarticular infection | - | 69 (60–78) | 20 (58.8) | [39] |
Study No. | Treatment | Number of Patients Treated [n (%)] | Number of Patients with P. aeruginosa | Resistance | Microbiological Cure [n (%)] | Mortality [n (%)] | References | |
---|---|---|---|---|---|---|---|---|
Sensitive Strains [n (%)] | Resistant Strains [n (%)] | |||||||
1 | Polymyxin B (combination) a | 104 | 0 (0) | 11 (10.5) | Carbapenem resistant | 20 | 50 | [28] |
2 | Polymyxin B (combination) b | 33 (34.7) | 0 (0) | 3 (9.1) 1,** | XDR | - | 0 (0) | [29] |
Polymyxin B (monotherapy) c | 68 (65.3) | 15 (22) ** | 0 (0) | XDR | ||||
3 | Empirical combination therapy c | 85 (85.0) | 0 (0) | 26 (31) 2 | MDR | - | 32 (37.6) | [30] |
Empirical monotherapy d | 15 (15) | 0 (0) | 5 (33) 2 | MDR | - | 7 (46.7) | ||
4 | Susceptible combination e | 40 (29.4) | 40 (29.4) 2 | 0 (0) | XDR | 36 (90) | 4 (10) | [31] |
Susceptible monotherapy f | 74 (54.4) | 74 (54.4) 2 | 0 (0) | XDR | 40 (54) | 38 (51) | ||
Resistant therapy g | 22 (16.2) | 0 (0) | 22 (16.2) 3 | XDR | 0 (0) | 22 (100) | ||
5 | Piperacillin–tazobactam with aminoglycoside | 16 (44.4) | 0 (0) | 16 (100) 1 | MDR | - | 3 (21.4) | [32] |
Meropenem | 14 (38.9) | 14 (100) | 0 (0) | MDR | - | 10 (71.4) | ||
Cefepime | 3 (7.4) | 3 (100) | 0 (0) | MDR | - | 0 (0) | ||
Cefepime with aminoglycoside | 2 (5.6) | 2 (100) | 0 (0) | MDR | - | 0 (0) | ||
Meropenem with aminoglycoside | 1 (2.8) | 1 (100) | 0 (0) | MDR | - | 1 (100) | ||
6 | Cefiderocol | 80 (67.8) | 12 (15) | 0 (0) | Carbapenem resistant | - | 2 (17) | [33] |
Cefiderocol combination h | 38 (32.2) | 10 (26) | 0 (0) | Carbapenem resistant | - | 2 (20) | ||
7 | Ceftolozane–tazobactam | 19 (100) | 19 (100) | 0 (0) | Carbapenem resistant | 14 (74) | 4 (21) | [34] |
9 | Colistin | 198 (48.8) | 13 (4) | 0 (0) | Carbapenem resistant | - | 4 (31) | [36] |
Colistin–meropenem | 208 (51.2) | 0 (0) | 8 (3.8) 1 | Carbapenem resistant | - | 2 (25) | ||
10 | Polymyxin B | 46 (62.2) | 46 (62.2) | 0 (0) ** | MDR | - | 25 (53) * | [37] |
Polymyxin B combination i | 28 (37.8) | 0 (0) | 28 (37.8) 2,** | MDR | - | 14 (50) * |
Study No. | Study Title | Study Design | Number of Patients | Clinical Indication | Age | Male Sex n (%) | Reference | ||
---|---|---|---|---|---|---|---|---|---|
Mean (SD) | Median (IQR) | ||||||||
13 | A randomised, double-blind, phase 3 study comparing the efficacy and safety of ceftazidime–avibactam plus metronidazole versus meropenem for complicated intra-abdominal infections in hospitalised adults in Asia | Multi | RCT | 431 | cIAI | 48.5 ± 16.8 | - | 294 (68.2) | [45] |
14 | Ceftazidime–avibactam Versus Doripenem for the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis: RECAPTURE, a Phase 3 Randomized Trial Program | Multi | RCT | 810 | cUTI | 51.4 ± 20.2 | - | 245 (30.2) | [46] |
15 | Efficacy and Safety of Ceftazidime–Avibactam Plus Metronidazole Versus Meropenem in the Treatment of Complicated Intra-abdominal Infection: Results from a Randomized, Controlled, Double-Blind, Phase 3 Program | Multi | RCT | 1043 | cIAI | 49.8 ± 17.5 | - | 658 (63.1) | [47] |
16 | Characterization of β-Lactamase Content of Ceftazidime-Resistant Pathogens Recovered during the Pathogen-Directed Phase 3 REPRISE Trial for Ceftazidime–Avibactam: Correlation of Efficacy against β-Lactamase Producers | Multi | RCT | 295 | Various | - | - | - | [48] |
17 | Clinical activity of ceftazidime–avibactam against MDR Enterobacteriaceae and Pseudomonas aeruginosa: pooled data from the ceftazidime–avibactam Phase III clinical trial programme | Multi | RCT | 1051 | Various | - | - | - | [49] |
18 | Ceftazidime–avibactam versus meropenem in nosocomial pneumonia, including ventilator-associated pneumonia (REPROVE): a randomised, double-blind, phase 3 non-inferiority trial | Multi | CT | 726 | VAP | - | 62·1 (16·6) | 542 (74.7) | [50] |
Study No. | Treatment | Number of Patients with P. aeruginosa [n (%)] | Ceftazidime Resistance Profile | Number of Patients Treated [n (%)] | Microbiological Cure [n (%)] | Clinical Cure [n (%)] | References |
---|---|---|---|---|---|---|---|
13 | Ceftazidime–avibactam | 11 (2.6) | Res | 1 (9.1) | - | 1 (100) | [45] |
Sus | 10 (90.9) | - | 10 (100) | ||||
14 | Doripenem | 37 (4.6) | Res | 6 (16.2) | 5 (83.3) | - | [46] |
Sus | 14 (37.8) | 10 (71.4) | - | ||||
Ceftazidime–avibactam | Res | 7 (18.9) | 5 (71.4) | - | |||
Sus | 10 (27.0) | 7 (70.0) | - | ||||
15 | Ceftazidime–avibactam and metronidazole | 68 (6.5) | Res | 2 (2.9) | - | 2 (100) | [47] |
Sus | 30 (44.1) | - | 27 (90.0) | ||||
Meropenem | Res | 4 (5.9) | - | 4 (100) | |||
Sus | 32 (47.0) | - | 30 (93.8) | ||||
16 | Ceftazidime–avibactam | 18 (6.1) | - | 13 (72.2) | 11 (84.6) | 11 (84.6) | [48] |
Best available treatment | - | 5 (27.8) | 3 (60.0) | 5 (100) | |||
17 | Ceftazidime–avibactam | 95 (9.0) | 66.1% Sus | 56 (58.9) | 32 (57.1) | - | [49] |
Carbapenem comparators | 39 (41.1) | 21 (53.8) | - | ||||
18 | Ceftazidime–avibactam | 77 (10.6) | 24.8% Sus | 42 (54.5) | 18 (42.9) | 27 (64.3) | [50] |
Meropenem | 35 (45.5) | 14 (40.0) | 27 (77.1) |
Search Term 1 | Search Term 2 | Search Term 3 |
---|---|---|
Pseudomonas aeruginosa | MDR | Combination therapy |
XDR | Multi-drug therapy | |
Carbapenem resistant | ||
Multi-drug resistant | ||
Antibiotic resistant | ||
Extensively drug resistant |
Inclusion Criteria | Exclusion Criteria |
---|---|
Title or abstract must include a reference to antibiotic combination therapy or a name of one or more antibiotic combinations | Articles without an available abstract or full text |
Title or abstract must include a reference to P. aeruginosa | Articles that were not published |
Title or abstract must include a reference to antibiotic-resistant strains | Articles indicating that P. aeruginosa or antibiotic combination therapy and its efficacy is not the main focus |
Must include in vitro or in vivo studies | Reviews, conference abstracts etc. |
Papers that include data on MIC or FIC | Articles that are primarily discussions of the topic of combination therapy and P. aeruginosa |
Papers that include monotherapy data | All surveys |
Papers that include clinical cure, mortality rate, or other clinical data | Articles with simulated testing methodologies |
Papers that include % susceptibility data |
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Jones, F.; Hu, Y.; Coates, A. The Efficacy of Using Combination Therapy against Multi-Drug and Extensively Drug-Resistant Pseudomonas aeruginosa in Clinical Settings. Antibiotics 2022, 11, 323. https://doi.org/10.3390/antibiotics11030323
Jones F, Hu Y, Coates A. The Efficacy of Using Combination Therapy against Multi-Drug and Extensively Drug-Resistant Pseudomonas aeruginosa in Clinical Settings. Antibiotics. 2022; 11(3):323. https://doi.org/10.3390/antibiotics11030323
Chicago/Turabian StyleJones, Frank, Yanmin Hu, and Anthony Coates. 2022. "The Efficacy of Using Combination Therapy against Multi-Drug and Extensively Drug-Resistant Pseudomonas aeruginosa in Clinical Settings" Antibiotics 11, no. 3: 323. https://doi.org/10.3390/antibiotics11030323