Table 3.
Prospective treatment options of Acinetobacter baumannii infections.
| Drugs | Type of research | Type of A. baumannii | Findings | References |
|---|---|---|---|---|
| Carbapenem +ampicillin+sulbactam+ | In vivo | Carbapenem-resistant | Combination therapy with ampicillin-sulbactam and meropenem is effective against skin and soft tissue infection | Hiraki et al., 2013 |
| In vivo | Multidrug-resistant | The combination of a carbapenem and ampicillin/sulbactam was associated with a better outcome than the combination of a carbapenem and amikacin, or a carbapenem alone | Kuo et al., 2007 | |
| Carbapenem +minocycline | In vitro | Multidrug-resistant | Minocycline in combination with rifampicin, imipenem, and colistin showed bactericidal synergy in most of the isolates which did not harbor the tetB gene, but the combinations were not synergistic in tetB-positive isolates | Rodriguez et al., 2015 |
| Carbapenem +tigecycline+colistin | Case report | Multidrug-resistant, colistin-susceptible | A patient with bacteremia had a favorable clinical outcome by a meropenem/colistin/tigecycline combination therapy | Candel et al., 2010 |
| Carbapenem +colistin | In vitro/case report | Extensively drug-resistant, colistin-susceptible | Effective; 80% of patients were treated successfully | Ozbek and Senturk, 2010 |
| In vitro | Multidrug-resistant, colistin-susceptible | Imipenem/colistin showed best synergy effects | Pongpech et al., 2010 | |
| In vitro/case report | Multidrug-resistant, colistin-susceptible | Meropenem/colistin can inhibit bacterial regrowth at 24 h | Lee C. H. et al., 2008 | |
| In vitro | Colistin-susceptible and colistin-resistant | Subinhibitory meropenem/colistin showed synergy against 49 of 52 strains at 24 h | Pankuch et al., 2008 | |
| In vitro | Extensively drug-resistant, colistin-susceptible | Combinations of colistin/rifampicin, colistin/meropenem, colistin/minocycline and minocycline/meropenem are synergistic | Liang et al., 2011 | |
| A retrospective study | Extensively drug-resistant, colistin-susceptible | Colistin/carbapenem and colistin/sulbactam resulted in significantly higher microbiological eradication rates, relatively higher cure and 14-day survival rates, and lower in-hospital mortality compared to colistin monotherapy in patients with bloodstream infections | Batirel et al., 2014 | |
| In vitro | Carbapenem-resistant, colistin-susceptible | Synergistic effects against all 12 isolates | Liu X. et al., 2016 | |
| In vivo | Extensively drug-resistant, colistin-susceptible and colistin-resistant | Colistin/fusidic acid and colistin/rifampicin were synergistic in a murine thigh-infection model; The colistin-meropenem combination was also effective when the colistin MIC is ≤32 mg/L. | Fan et al., 2016 | |
| In vitro | Extensively drug-resistant | The daptomycin-colistin combination was the most effective; the colistin/imipenem combination was also effective | Cordoba et al., 2015 | |
| Carbapenem +colistin+rifampicin | Case report | Multidrug-resistant, colistin-susceptible | Successful treatment by a meropenem/colistin/rifampicin combination therapy in a case of multifocal infection | Biancofiore et al., 2007 |
| Carbapenem+plazomicin | In vitro | Carbapenem-resistant | Synergistic activity | Garcia-Salguero et al., 2015 |
| Imipenem+polymyxin B | In vitro | Carbapenem-resistant | Doripenem, meropenem, or imipenem displayed similar pharmacodynamics in combination with polymyxin B | Lenhard et al., 2016b |
| Meropenem+ polymyxin B | In vitro | Multidrug-resistant | Combinations of polymyxin B/meropenem and polymyxin B/meropenem/fosfomycin showed high synergistic activity | Menegucci et al., 2016 |
| In vitro/in vivo | Carbapenem-resistant | Intensified meropenem dosing in combination with polymyxin B synergistically killed carbapenem-resistant strains, irrespective of the meropenem MIC | Lenhard et al., 2016a | |
| In vitro | Carbapenem-resistant | Doripenem, meropenem, or imipenem displayed similar pharmacodynamics in combination with polymyxin B | Lenhard et al., 2016b | |
| Doripenem+tigecycline | In vitro | Multidrug-resistant, doripenem-resistant | Synergistic activity | Principe et al., 2013 |
| Doripenem+colistin | In vitro | Multidrug-resistant, doripenem-resistant | Synergistic activity | Principe et al., 2013 |
| Doripenem+polymyxin B | In vitro | Carbapenem-resistant | Doripenem, meropenem, or imipenem displayed similar pharmacodynamics in combination with polymyxin B | Lenhard et al., 2016b |
| In vitro | Polymyxin-heteroresistant | The polymyxin B/doripenem combination resulted in rapid and extensive initial killing within 24 h, which was sustained over 10 days | Rao et al., 2016a | |
| Doripenem+amikacin | In vitro | Multidrug-resistant, doripenem-resistant | Synergistic activity | Principe et al., 2013 |
| Ampicillin+sulbactam | In vitro/in vivo | Multi-drug resistant | Ampicillin/sulbactam therapy significantly decreased the risk of death in patients with bloodstream infections | Smolyakov et al., 2003 |
| Sulbactam+colistin | A retrospective study | Extensively drug-resistant, colistin-susceptible | Colistin/carbapenem and colistin/sulbactam resulted in significantly higher microbiological eradication rates, relatively higher cure and 14-day survival rates, and lower in-hospital mortality compared to colistin monotherapy in patients with bloodstream infections | Batirel et al., 2014 |
| A retrospective study | Multidrug-resistant | The colistin/sulbactam combination therapy is promising in patients with ventilator-associated pneumonia | Kalin et al., 2014 | |
| Tazobactam+colistin | In vivo | Colistin-susceptible | Tazobactam plus colistin showed synergy | Sakoulas et al., 2016 |
| Minocycline+colistin | In vitro | Extensively drug-resistant | Combinations of colistin/rifampicin, colistin/meropenem, colistin/minocycline and minocycline/meropenem are synergistic | Liang et al., 2011 |
| In vitro/in vivo | Minocycline-resistant | Minocycline/colistin synergistically killed minocycline-resistant isolates; minocycline/colistin also significantly improved the survival of mice and reduced the number of bacteria present in the lungs of mice | Yang et al., 2016 | |
| In vitro | Multidrug-resistant | Minocycline in combination with rifampicin, imipenem, and colistin showed bactericidal synergy in most of the isolates which did not harbor the tetB gene, but the combinations were not synergistic in tetB-positive isolates | Rodriguez et al., 2015 | |
| Minocycline+rifampicin | In vivo | Multidrug-resistant | Synergistic effect of minocycline/rifampicin and minocycline/amikacin combinations in a mouse lung infection model | He S. et al., 2015 |
| In vitro | Multidrug-resistant | Minocycline in combination with rifampicin, imipenem, and colistin showed bactericidal synergy in most of the isolates which did not harbor the tetB gene, but the combinations were not synergistic in tetB-positive isolates | Rodriguez et al., 2015 | |
| Minocycline+amikacin | In vivo | Multidrug-resistant | Synergistic effect of minocycline/rifampicin and minocycline/amikacin combinations in a mouse lung infection model | He S. et al., 2015 |
| Tigecycline+colistin | In vitro | Carbapenem-resistant, colistin-susceptible | Good synergy | Ozbek and Senturk, 2010; Sheng et al., 2011 |
| In vitro | Extensively drug-resistant, colistin-susceptible | Good synergy | Dizbay et al., 2010 | |
| In vitro | Tigecycline-non-susceptible | Good synergy | Principe et al., 2009 | |
| In vitro | Carbapenem-resistant, colistin-susceptible and colistin-resistant | Good synergy | Peck et al., 2012 | |
| In vitro/in vivo | Extensively drug-resistant | In vitro synergistic activity; no statistically significant differences were found between colistin, tigecycline, and combination treatments in terms of efficacy on bacterial counts in lung tissue of a rat pneumonia model | Mutlu Yilmaz et al., 2012 | |
| Tigecycline+polymyxin B | In vitro | Carbapenem-resistant, polymyxin-heteroresistant | Combination of polymyxin B-with higher tigecycline concentrations result in sustained bactericidal activity | Rao et al., 2016b |
| In vitro | Carbapenem-resistant | Synergistic effects in combination therapy with simulated exposures of polymyxin B and tigecycline at an aggressive dose | Hagihara et al., 2014 | |
| Tigecycline+amikacin | In vitro | Multidrug-resistant | Synergistic bactericidal activities | Moland et al., 2008 |
| Colistin+rifampicin | In vitro/in vivo | Multidrug-resistant, colistin-susceptible | Efficacy in vitro and in experimental models of pneumonia and meningitis | Pachon-Ibanez et al., 2010 |
| Case report | Carbapenem-resistant, colistin-susceptible | Efficacy in 7 of 10 patients with ventilator-associated pneumonia | Song et al., 2008 | |
| Case report | Multidrug-resistant, colistin-susceptible | Efficacy in 22 of 29 critically ill patients with pneumonia and bacteremia | Bassetti et al., 2008 | |
| In vivo | Multidrug-resistant, colistin-susceptible | Synergistic effect in prolonging survival | Pantopoulou et al., 2007 | |
| Clinical trial | Multidrug-resistant, colistin-susceptible | Favorable for all 26 nosocomial infection patients | Motaouakkil et al., 2006 | |
| In vitro | Carbapenem-resistant, colistin-susceptible | Effective for strains highly resistant to imipenem and moderately resistant to rifampicin | Montero et al., 2004 | |
| In vitro | Multidrug-resistant, colistin-susceptible | Synergistic effect against 11 of 13 isolates | Hogg et al., 1998 | |
| In vitro | Extensively drug-resistant | Combinations of colistin/rifampicin, colistin/meropenem, colistin/minocycline and minocycline/meropenem are synergistic | Liang et al., 2011 | |
| In vitro | Multidrug-resistant, colistin-susceptible | Colistin/rifampicin was fully synergistic against 4 of 5 isolates; colistin/meropenem and colistin/azithromycin were synergistic against 3 of 5 isolates; colistin/doxycycline was partially synergistic or additive against 5 isolates | Timurkaynak et al., 2006 | |
| Case report | Carbapenem-resistant, colistin-susceptible | Rifampicin/colistin and ampicillin/sulbactam resulted in microbiological clearance in 9 of 14 critically ill patients | Petrosillo et al., 2005 | |
| In vitro | Carbapenem-resistant, colistin-heteroresistant | Rifampicin/colistin and imipenem/colistin were synergistic against heteroresistant isolates and prevented the development of colistin-resistant strains | Rodriguez et al., 2010 | |
| Case report | Carbapenem-resistant, colistin-susceptible | Synergistic effect in patients with ventilator-associated pneumonia | Aydemir et al., 2013 | |
| In vivo | Extensively drug-resistant, colistin-susceptible and colistin-resistant | Colistin/fusidic acid and colistin/rifampicin were synergistic in a murine thigh-infection model; The colistin-meropenem combination was also effective when the colistin MIC is ≤32 mg/L. | Fan et al., 2016 | |
| In vitro | Colistin-resistant | The most effective combinations were colistin-rifampin and colistin-teicoplanin; both combinations showed synergistic effect against 8 of 9 colistin-resistant strains | Bae et al., 2016 | |
| Colistin+teicoplanin | In vitro/in vivo | Multidrug-resistant, colistin-susceptible | Synergistic effect of colistin/daptomycin and colistin/teicoplanin in a mouse model | Cirioni et al., 2016 |
| In vitro | Multidrug-resistant, colistin-susceptible | Significant synergy | Wareham et al., 2011 | |
| In vitro | Colistin-resistant | The most effective combinations were colistin-rifampin and colistin-teicoplanin; both combinations showed synergistic effect against 8 of 9 colistin-resistant strains | Bae et al., 2016 | |
| Colistin+daptomycin | In vitro/in vivo | Multidrug-resistant, colistin-susceptible | Synergistic effect of colistin/daptomycin and colistin/teicoplanin in a mouse model | Cirioni et al., 2016 |
| In vitro | Extensively drug-resistant | The daptomycin-colistin combination was the most effective; the colistin/imipenem combination was also effective | Cordoba et al., 2015 | |
| Colistin+vancomycin | In vitro/in vivo | Multidrug-resistant, colistin-susceptible | Highly active both in vitro and in an animal model of Galleria mellonella | Hornsey and Wareham, 2011 |
| Colistin+fosfomycin | In vitro | Carbapenem-resistant, colistin-susceptible | Good synergy; no synergy between colistin and sulbactam, colistin and imipenem | Santimaleeworagun et al., 2011 |
| Colistin+fusidic acid | In vitro | Carbapenem-resistant, colistin-susceptible and colistin-resistant | In vitro synergy between colistin and fusidic acid that is comparable to the synergy between colistin and vancomycin; the synergy with fusidic acid is strain-dependent and applicable to strains for which the colistin MICs are relatively low | Bowler et al., 2016 |
| In vitro | Carbapenem-resistant, colistin-susceptible and colistin-resistant | Robust synergy between fusidic acid and colistin against multidrug-resistant clinical strains, including some colistin-resistant strains | Phee et al., 2015 | |
| In vivo | Extensively drug-resistant, colistin-susceptible and colistin-resistant | Colistin/fusidic acid and colistin/rifampicin were synergistic in a murine thigh-infection model; The colistin-meropenem combination was also effective when the colistin MIC is ≤32 mg/L. | Fan et al., 2016 | |
| Colistin+amikacin | Case report | Multidrug-resistant, colistin-susceptible | Successful clinical and microbiological outcomes | Fulnecky et al., 2005 |
| Colistin+trimethoprim-sulfamethoxazole | In vitro | Carbapenem-resistant | Colistin/trimethoprim-sulfamethoxazole killed effectively all carbapenem-resistant strains | Nepka et al., 2016 |
| Polymyxin B+netropsin | In vitro/in vivo | Colistin-resistant | The survival of infected Galleria mellonella was significantly higher when treated with polymyxin B and netropsin in combination than when treated with polymyxin B or netropsin alone | Chung et al., 2016 |
| Trimethoprim-sulfamethoxazole | In vitro | Carbapenem-resistant | Trimethoprim-sulfamethoxazole killed effectively all carbapenem-resistant strains | Nepka et al., 2016 |
| Novobiocin | In vitro | Carbapenem-susceptible | Inhibition of frequency of the occurrence of rifampin resistance mutants | Jara et al., 2015 |
| Bacteriophages | In vitro/in vivo | Carbapenem-resistant, carbapenem-susceptible | Strong lytic activities and the improvement of survival rates | Jeon et al., 2016; Kusradze et al., 2016 |
| Endolysin (LysABP-01)+colistin | In vitro | Multidrug-resistant | Synergistic activity | Thummeepak et al., 2016 |
| Artilysins | In vitro | Carbapenem-resistant, carbapenem-susceptible | Artilysins are effective in vitro and in vivo | Briers et al., 2014; Yang et al., 2015; Defraine et al., 2016; Thandar et al., 2016 |
| Antimicrobial peptides | In vitro | Multidrug-resistant | Good antimicrobial activities | Pires et al., 2015; Barksdale et al., 2016 |
| Rose bengal+ carbapenem | In vitro | Carbapenem-resistant | Imipenem or meropenem with rose bengal showed synergistic effects | Chiu et al., 2016 |
| β-Aminoketone (MD3)+colistin | In vitro | Colistin-susceptible, colistin-resistant | Synergistic effect targeting to strains with specific colistin resistance mechanisms; synergy against both colistin-susceptible strains and colistin-resistant strains with mutations in pmrB and phosphoethanolamine modification of lipid A, but not against colistin-resistant strains with loss of lipopolysaccharide | Martinez-Guitian et al., 2016 |
| Bulgecin A+ carbapenem | In vitro | Carbapenem-resistant | Synergistic activity | Skalweit and Li, 2016 |
| Farnesol+colistin | In vitro | Colistin-resistant | Farnesol increased sensitivity to colistin for colistin-resistant strains | Kostoulias et al., 2015 |
| Oleanolic acid+gentamicin or kanamycin | In vitro | Carbapenem-susceptible | Synergistic activity | Shin and Park, 2015 |
| Cyanide 3-chlorophenylhydrazone (CCCP)+colistin | In vitro | Colistin-resistant | CCCP reversed colistin resistance and inhibited the regrowth of the resistant subpopulation | Ni et al., 2016 |
| In vitro | Colistin-resistant | Synergistic activity | Park and Ko, 2015 | |
| ABEPI1 or ABEPI2+minocycline | In vitro | Carbapenem-susceptible | Synergistic activity | Blanchard et al., 2014 |
| Gallium nitrate | In vitro/in vivo | Multidrug-resistant | Good antimicrobial activities; protection of Galleria mellonella larvae from lethal A. baumannii infection; synergistic activity with colistin | Antunes et al., 2012 |
| Gallium protoporphyrin IX | In vitro/in vivo | Multidrug-resistant | Good antimicrobial activities | Arivett et al., 2015 |
| Gallium nitrate+colistin | In vitro/in vivo | Multidrug-resistant | Good antimicrobial activities; protection of Galleria mellonella larvae from lethal A. baumannii infection; synergistic activity with colistin | Antunes et al., 2012 |
| D-amino acids | In vitro/in vivo | Carbapenem-susceptible | Some D-amino acids (D-histidine and D-cysteine) can inhibit bacterial growth, biofilm formation and adherence to eukaryotic cells | Rumbo et al., 2016 |
| Bifidobacterium breve strain Yakult | In vivo | Multidrug-resistant | Protection against fatal intestinal infection in a murine infection model | Asahara et al., 2016 |
| Clarithromycin | In vivo | Multidrug-resistant | Inhibition of bacterial growth and biofilm formation; immunomodulator | Konstantinidis et al., 2016 |
| Lysophosphatidylcholine+carbapenem | In vivo | Multidrug-resistant strain | Lysophosphatidylcholine in combination with colistin, tigecycline, or imipenem markedly enhanced the bacterial clearance from the spleen and lungs and reduced bacteremia and mouse mortality rates | Parra Millan et al., 2016 |
| Lysophosphatidylcholine+tigecycline | In vivo | Multidrug-resistant strain | Lysophosphatidylcholine in combination with colistin, tigecycline, or imipenem markedly enhanced the bacterial clearance from the spleen and lungs and reduced bacteremia and mouse mortality rates | Parra Millan et al., 2016 |
| Lysophosphatidylcholine+colistin | In vivo | Multidrug-resistant strain | Lysophosphatidylcholine in combination with colistin, tigecycline, or imipenem markedly enhanced the bacterial clearance from the spleen and lungs and reduced bacteremia and mouse mortality rates | Parra Millan et al., 2016 |