In vitro Synergistic Activity of Colistin-Based Antimicrobial Combinations against Extensively Drug-Resistant (XDR) Acinetobacter baumannii from a Tertiary Hospital in Greece ^†

1. Background

Over the past years, Acinetobacter baumannii has emerged as a serious nosocomial pathogen especially due to its extensively resistant antimicrobial profile. Colistin is currently used as one of the last resort agents to treat the related infections, but resistance due to monotherapy has increasingly been reported [1]. We evaluated the in vitro susceptibility of colistin-based antimicrobial combinations against extensively drug-resistant (XDR) A. baumannii isolates from a tertiary hospital in Northern Greece.

2. Materials

One hundred A. baumannii single clinical isolates with resistance to carbapenems and colistin between March and October 2021 were included in the study; 46 were isolated from blood, 41 from bronchoalveolar secretions, 6 from urine, 3 from central lines, 3 from skin and soft tissues, and 1 from cerebrospinal fluid. Antimicrobial susceptibility testing was performed by Vitek2 (bioMérieux, Lyon, France), whereas tigecycline, rifampicin, and daptomycin were tested with MIC test strip (Liofilchem, Italy), and colistin was tested with broth microdilution method (Liofilchem, Roseto degli Abruzzi, Italy). MIC range, MIC50, MIC90, and resistance rates were calculated according to EUCAST breakpoints. The MIC test strip fixed ratio method was used for the synergistic activity for three antimicrobial combinations of colistin with either meropenem, rifampicin, or daptomycin [2]. The results were interpreted using fractional inhibitory concentration index (FICI). ‘Synergy’, ‘additivity’, ‘indifference’, and ‘antagonism’ were interpreted when the FICI was ≤0.5, >0.5–≤1, >1–≤4, and >4, respectively [3].

3. Results

All the studied strains displayed high rates of resistance to major classes of antimicrobials (>97%) with 100% resistance to colistin (

Table 1. Antimicrobial profile of Acinetobacter baumannii isolates. NA: not applicable.

Antibiotic	Number of Strains Tested	MIC Range (mg/L)	MIC50 (mg/L)	MIC90 (mg/L)	Resistance (%)
Meropenem	100	8–16	16	16	100
Imipenem	100	8–16	16	16	100
Ciprofloxacin	36	4	4	4	100
Amikacin	36	4–64	64	64	97.22
Gentamicin	35	1–16	16	16	97.14
Trimethoprim/Sulfamethoxazole	36	0.75–320	320	320	97.22
Ampicillin/Sulbactam	67	16–32	32	32	NA
Colistin	100	4–64	16	16	100
Tigecycline	97	0.05–8	3	6	NA
Rifampicin	81	2–256	6	32	NA
Daptomycin	30	256	256	256	NA

). MIC50/MIC90 (mg/L) for tigecycline were 3/6, for ampicillin/sulbactam 32/32, for rifampicin 6/32, and for daptomycin 256/256. All 100 isolates were tested for colistin/meropenem combination exhibiting 87% synergy (FICI range = 0.00078–0.5) and 13% additivity (FICI range = 0.56–0.84). Although rifampicin and daptomycin are typically inactive against Gram-negative bacteria, higher rates of synergy were observed using colistin/rifampicin combination with 93.75% (75/80) synergy (FICI range = 0.002–0.47), 3.75% (3/80) additivity (FICI range = 0.56–0.62), and 2.5% (2/80) indifference (FICI range = 1–1.42). Colistin/daptomycin combination was tested in 30 isolates, resulting in 90% (27/30) synergy (FICI range = 0.017–0.42) and 10% (3/30) additivity (FICI range = 0.51–0.76).

4. Conclusions

In vitro colistin-based combinations with either rifampicin or daptomycin or meropenem resulted in high synergy rates, rendering them a valuable option for the treatment of colistin-resistant A. baumannii infections.