In vitro evaluation of human intravenous immunoglobulin in combination with antimicrobials and human serum against multidrug-resistant isolates of Acinetobacter baumannii

• Published in: Brazilian journal of microbiology Vol. 54; no. 4; pp. 2845 - 2856
• Main Authors: de Lima, Fernanda Cristina Gomes, de Araújo, Alberon Ribeiro, do Nascimento, Amanda Vasconcelos, Bezerra Cavalcanti, Carmelita de Lima, Oliveira Júnior, Jorge Belém, Sandes, Jana Messias, da Silva, Everton Morais, de Freitas, Catarina Fernandes, Veras, Dyana Leal, Alves, Luis Carlos, Brayner, Fábio André
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.12.2023; Springer Nature B.V
• Subjects: Acinetobacter baumannii; Acinetobacter Infections - drug therapy; Acinetobacter Infections - microbiology; Amikacin; Amikacin - pharmacology; Amikacin - therapeutic use; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Anti-Infective Agents - pharmacology; Antimicrobial agents; Bacteria; Bacterial diseases; Bacterial infections; Binding; Biomedical and Life Sciences; Cell morphology; Clinical Microbiology - Research Paper; Colistin; Colistin - pharmacology; Complement activation; Complement system; Cytology; Drug Resistance, Multiple, Bacterial; Drug Synergism; Extravasation; Fluorescence; Food Microbiology; Humans; IgG antibody; Immune system; Immunofluorescence; Immunoglobulin G; Immunoglobulins; Immunoglobulins, Intravenous - pharmacology; Immunoglobulins, Intravenous - therapeutic use; Infections; Intravenous administration; Life Sciences; Medical Microbiology; Meropenem; Meropenem - pharmacology; Meropenem - therapeutic use; Microbial Ecology; Microbial Genetics and Genomics; Microbial Sensitivity Tests; Microbiology; Monocytes; Morphology; Multidrug resistance; Multidrug resistant organisms; Mycology; Neutralization; Opsonization; Phagocytosis; Scanning electron microscopy; Intravenous immunoglobulin; Scanning electron microscopy; Indirect immunofluorescence; Phagocytosis rates; Acinetobacter baumannii
• DOI: 10.1007/s42770-023-01153-5
• ISSN: 1517-8382; 1678-4405

The high incidence of multidrug-resistant (MDR) Acinetobacter baumannii has been a challenge for health worldwide, due to the reduction of therapeutic options, making the use of antimicrobial combinations necessary for the treatment, such as meropenem, amikacin, and colistin. Antibodies against bacterial species, mainly immunoglobulins G (IgG), are produced for acting as effector mechanisms (neutralization, opsonization, phagocytosis, and complement system activation). Some studies have demonstrated promising results of IgG in combination with antimicrobial preparations against bacterial infections, in which the direct action of IgG has restored the immune system balance. Serious problem caused by the increase of MDR A. baumannii isolates results in a constant search for therapeutic alternatives to defeat these infections. However, this study aims to verify in vitro the phagocytosis rate of the A. baumannii –infected human monocytes, as well as to analyze possible morphological changes induced by intravenous immunoglobulin G (IVIG) with human serum in association with antimicrobials. The phagocytosis rate and bacterial cell binding capacity of IVIG were determined for two A. baumannii isolates submitted to 4 mg/mL of human IVIG alone and in combination with different sub-minimum inhibitory concentrations (sub-MICs) of meropenem, amikacin, and colistin and processed for indirect immunofluorescence. Subsequently, these isolates were resubmitted and coupled with human serum and processed for scanning electron microscopy. There was no statistical difference for phagocytosis rates in the isolates tested. Bacterial isolates showed alterations in cell morphology when exposed to IVIG/human serum alone and in combination with antimicrobials such as alteration in shape, wrinkling, membrane depression, and especially cell rupture with extravasation of cytoplasmic material. The isolates visually differed in the IVIG binding to the bacterial cell, with higher fluorescence intensity, which corresponds to the highest IVIG binding, in the isolate more sensitive to meropenem, amikacin, and colistin. No differences between treatments were observed in the IVIG binding to the bacterial cell. The combined action of IVIG with meropenem, amikacin, and colistin against A. baumannii MDR isolates induced several bacterial cell damages. And when associated with human serum, a massive destruction of cells can be observed. These results may suggest the analysis of the use of IgG preparations for the treatment of A. baumannii MDR infections.