Utility of lytic bacteriophage in the treatment of multidrug-resistant <i> Pseudomonas aeruginosa</i> septicemia in mice

Drug resistance is the major cause of increase in morbidity and mortality in neonates. One thousand six hundred forty-seven suspected septicemic neonates were subjected for microbiological analysis over a period of 5 years. Forty-two <i>P. aeruginosa</i> were isolated and the antibiogram revealed that 28 <i>P. aeruginosa</i> were resistant to almost all the common drugs used (multidrug-resistant). The emergence of antibiotic-resistant bacterial strains is one of the most critical problems of modern medicine. As a result, a novel and most effective approaches for treating infection caused by multidrug-resistant bacteria are urgently required. In this context, one intriguing approach is to use bacteriophages (viruses that kill bacteria) in the treatment of infection caused by drug-resistant bacteria. In the present study, the utility of lytic bacteriophages to rescue septicemic mice with multidrug-resistant (MDR) <i>P. aeruginosa</i> infection was evaluated. MDR <i>P</i>. <i>aeruginosa</i> was used to induce septicemia in mice by intraperitoneal (i.p.) injection of 10⁷ CFU. The resulting bacteremia was fatal within 48 hrs. The phage strain used in this study had lytic activity against a wide range of clinical isolates of MDR <i>P. aeruginosa.</i> A single i.p. injection of 3 x 10⁹ PFU of the phage strain, administered 45 min after the bacterial challenge, was sufficient to rescue 100&#x0025; of the animals. Even when treatment was delayed to the point where all animals were moribund, approximately 50&#x0025; of them were rescued by a single injection of this phage preparation. The ability of this phage to rescue septicemic mice was demonstrated to be due to the functional capabilities of the phage and not to a nonspecific immune effect. The rescue of septicemic mice could be affected only by phage strains able to grow <i>in vitro</i> on the bacterial host used to infect the animals and when such strains are heat-inactivated, they lose their ability to rescue the infected mice. Multidrug-resistant bacteria have opened a second window for phage therapy. It would seem timely to begin to look afresh at this approach. A scientific methodology can make phage therapy as a stand-alone therapy for infections that are fully resistant to antibiotics.