**5.6 Urinary tract infections**

*Acinetobacter baumannii* is a Gram-negative nosocomial pathogen involved in human bacterial, meningitis, and respiratory infections (**Table 5**). A 68-year-old man with diabetes developed necrotizing pancreatitis, a complication of a pancreatic pseudocyst infected by the multi-drug resistant strain of *A. baumannii* [80]. Despite antibiotic treatment, the patient's condition deteriorated rapidly. Bacteriophage treatment has been initiated as part of an urgent new drug protocol. Commercially available Pyo bacteriophage solution (prophages; 20 mL) was used to enhance the treatment effect in the urinary tract infections in patients undergoing intravenous bacteriophage therapy TURP [112]. At very low concentrations of bacteriophage PP1131, the burden of the bacterium *P. aeruginosa* in burn wounds was less than the standard of care [83]. In another case of treatment, a solution consisting of 107 –10<sup>9</sup> PFU/mL of the bacteriophages was introduced 2 times per 24 hours i.e., 8.00, 20.00 for 7 days, soon after surgery [113]. The patients were requested to hold the solution in the bladder for 30–60 min to control *Staphylococcus aureus, E. coli, Streptococcus* spp. (Streptococci group D renamed as *Enterococcus* spp.), *Pseudomonas aeruginosa*, *Proteus* spp. of urological infections of urinary tract infections after transurethral resection of the prostate. After treatment, four patients presented no significant bacterial growth while *E. coli* and *Enterococcus* spp. were still detected in the urine culture of four and one patient, individually. Bacterial counts decreased in six out of nine patients (67%), after the phage therapy treatment. No bacteriophage-associated adverse events have been detected. In one of the patients, (cephalosporin was given on day 3 after the development of fever (>38.0°C), the symptoms disappeared within 48 hours. Urine culture showed *P. aeruginosa* [113]. Intravascular bacteriophage therapy is no less than standardprotective care of antibiotic treatment, but it is no better than placebo bladder irrigation in terms of efficacy or safety in treating UTIs in patients with eruption. The data indicated that infection of the six lytic bacteriophages, each at a titre of 10 PFU mL 1.20 mL (<sup>2</sup> <sup>10</sup><sup>7</sup> p.f.u.) Pyo-phages were self-sustaining and selflimiting, with the phages decreasing in number along with the viable target organisms in which they replicated [114].

### **5.7 Pneumoniae**

Bacterial pneumonia is an infection of *Streptococcus pneumoniae, Klebsiella pneumonia*, and *Mycoplasma pneumoniae* in each lung inflicting irritation in the alveoli or air sacs stuffed with fluid or pus, making it is hard to breathe. Pneumonia Phage (Φ2 (KpJH46Φ2)), *Klebsiella pneumoniae* examined for K Joint affected person against prostatic infection [43, 44], (**Tables 1** and **3**). The affected person received 6.3 <sup>10</sup><sup>10</sup> phages in 50 ml of normal saline solution and forty, doses every week. As a result of the treatment of phage, the local characteristics and *K. pneumoniae* infection symptoms had been resolved, the overall performance also had been restored. The affected person did now not experience any adverse effects related to treatment and remained asymptomatic within 34 weeks of completion of phage therapy when receiving minocycline. Intravenous injection of a single dose of <sup>2</sup> <sup>10</sup><sup>9</sup> PFU of lytic bacteriophage of multidrug resistance *Klebsiella pneumoniae* KP



### **Table 5.**

*Therapeutic bacteriophages for antibiotic-resistant Urinary tract bacterial infections.*

1513/mouse protected animals from sublethal pneumonia. The severity of pneumonia has been shown to be low. Compared with the untreated control, Phage-treated mice are more unlikely to develop *Klebsiella pneumoniae* in the lungs. Phage KP 1513, has a significant antibacterial impact *in vitro* and *in vivo*, and its host *K. pneumoniae* is multi-drug-resistant. Phage KP 1513 can be used as choice to antibiotic treatment for pneumonia caused by *Klebsiella pneumoniae* [44]. Aerophages/ Intravenous injection of bacteriophages saved 50% of animals from severe MRSA pneumonia compared to placebo controls. In contrast, administration of bacteriophages by both the aerophages and IV phages rescued 91% of animals, which used to be greater than either monotherapy. Standard-of-care antibiotic linezolid saved 38% of animals [79]. The natural phages belonging to Caudovirales including order Siphoviridae, Myoviridae, and Podoviridae had been separated from the clinical strains of multidrug-resistant *K. pneumoniae*. *In vitro* lytic activity of phages on isolated bacteria revealed 70% coverage of 33 isolated antibiotic-resistant strains, of which 50% targeted multiple phages. Overall, these results suggest the possibility of phage detection by strong action against antibiotic-resistant KP strains and may furnish a new therapeutic approach to the treatment of ESBL and CRKP infections [115].

### **5.8 Diarrhoea**

Bacterial diarrhea occurs in humans if infected with bacteria such as *Salmonella* and *E. coli*. Symptoms of diarrhea appears if the lining of the intestine is unable to absorb fluid, or secretes fluid, and bowel activities become loose or watery 3 or more times a day. Loss of fluid and electrolytes were encountered as a result of diarrhea [42]. In a placebo-controlled clinical trial, oral administration of Coliphage 10<sup>9</sup> PFU against *Escherichia coli* 3 times/day/4 days showed no significant clinical benefit between the control and test group (**Table 1**) [51, 83]. Fifteen healthy volunteers with *Escherichia coli* diarrhea received *Escherichia coli* phage T4 dose (10<sup>3</sup> PFU/ml), high-phage dose (10<sup>5</sup> PFU/ml), and fifteen healthy adult volunteers received low dose *Escherichia coli* phage (PG4). Volunteers receiving high-dose (10<sup>5</sup> PFU/ml), high-dose phage showed stool phage 1 day after exposure. This prevalence is only 50% in those receiving low-dose bacteriophages. One week after the 2-day course of oral phage application, no faecal phage was detected. Oral phage

application did not reduce the total stool *E. coli* count. In addition, no significant phage T4 replication was found in the early *E. coli* population. The study described the production of phage cocktails for use in clinical trials and Phage preparations are already entering clinical trials [51, 83]. Phage therapy has recently been reemphasized due to the severity of drug-resistant bacterial infections [9]. Antibiotics alone or with antibiotics have been used successfully to treat a variety of bacterial infections, including atherosclerosis, lung and lung infections, chronic otitis, skin burn infections and enteric infections [65, 68, 80, 92, 116]. In contrast, other clinical reports have shown that bacteriophages are less effective than expected due to inadequacy or coverage for topical bacterial infections and ETEC (Enterotoxigenic *Escherichia coli*) [42, 83]. In addition, published reports show no side effects in clinical trials or no adversative actions associated to phage application [51, 117].
