Background: Due to its rapid resistance development and ability to form biofilms, treatment of Pseudomonas aeruginosa infections is becoming more complicated by the day. Drug combinations may help reduce both resistance and biofilm formation. Methods: Using the microtiter plate assay, we investigated the in vitro inhibition of biofilm formation and the disruption of preformed biofilms in multidrug-resistant and extensively drug-resistant clinical isolates of P. aeruginosa in the presence of peak plasma levels of eight antipseudomonal antibiotics alone and in combination with fosfomycin: ceftazidime, piperacillin/tazobactam, cefepime, imipenem, gentamicin, amikacin, ciprofloxacin and colistin. Results: Combination therapy was significantly superior to monotherapy in its inhibition of biofilm formation. The highest inhibition rates were observed for combinations with colistin, cefepime and ceftazidime. Conclusion: Our results support fosfomycin combination therapy as an enhanced prophylactic option. Moreover, combinations with β-lactam antibiotics and colistin demonstrated a more potent inhibition effect on biofilm formation than protein synthesis inhibitors.

Pseudomonas aeruginosa is a leading cause of nosocomial infections. Given the constant rise in resistance, adequate therapy is increasingly demanding. Fosfomycin recently became an appealing treatment option of bacterial infections due to multidrug-resistant bacteria (MDR). So far, fosfomycin synergy with other antibiotics has been assessed in studies, but only a limited number focused on MDR P. aeruginosa and on the effect of these combinations on the duration of the postantibiotic effect (PAE). We investigated synergy of fosfomycin with an array of antipseudomonal antibiotics using gradient diffusion strip cross method and time-kill method, and their effect on the duration of PAE against 51 variously resistant P. aeruginosa isolates. The highest rate of synergy was observed for combination with ceftazidime (23.4%) and gentamicin (19.1%). The PAE of antibiotic combinations was superior to that of the drugs alone. Our findings indicate that fosfomycin combination therapy may be a valuable treatment alternative.

Infections within the intensive care unit (ICU) continue to be a major contributor to morbidity and mortality throughout Europe. Critically ill patients, oftentimes presenting with organ failure, having frequent interactions with invasive medical devices, and by receiving multiple antimicrobial agents are particularly susceptible to infections. Having knowledge of pathogen-specific epidemiology in ICUs across Europe and their antimicrobial resistance patterns is of utmost importance to choosing the right empirical therapy. Challenge posed by multidrug-resistant organisms, especially Gram-negative bacteria, is easier to tackle with infection prevention strategies, antimicrobial stewardship initiatives, and collaborative multidisciplinary care in place within the ICU setting.

This study aimed to examine the motility, biofilm production, endotoxin release, and antibiotic resistance of 81 Ralstonia pickettii isolates collected from different pharmaceutical water systems in Croatia. Swimming and twitching motility were detected in all isolates, while swarming was not observed. Biofilm production was detected in approximately 40 % of the isolates under the tested conditions. Notably, extracellular polymeric substance (EPS) production was a common trait among all isolates. Endotoxin production was detected with the Limulus Amoebocyte Lysate test. Antibiotic susceptibility testing revealed consistent resistance to colistin, as well as significant resistance rates to β-lactam antibiotics, ertapenem, amoxicillin/clavulanic acid, ticarcillin and ampicillin. High susceptibility to first-generation cephalosporins, cephalexin, cefoxitin and chloramphenicol was observed. All isolates were susceptible to tigecycline and tetracycline. The isolates were grouped into three genetically closely related clusters, yet notable phenotypic diversity in biofilm production and antibiotic susceptibility persisted within these groups. The study highlights R. pickettii ’s adaptability in pharmaceutical water systems, marked by its motility, biofilm-forming capabilities, and multidrug resistance. These results emphasise the importance of rigorous monitoring of water systems to reduce transmission risks and prevent the emergence of resistant strains in clinical environments.