Treatment Of Bacterial Cystitis Research Articles

Fabrication of levofloxacin-loaded porcine acellular dermal matrix hydrogel and functional assessment in urinary tract infection

Bacterial cystitis, a commonly occurring urinary tract infection (UTI), is renowned for its extensive prevalence and tendency to recur. Despite the extensive utilization of levofloxacin as a conventional therapeutic approach for bacterial cystitis, its effectiveness is impeded by adverse toxic effects, drug resistance concerns, and its influence on the gut microbiota. This study introduces Lev@PADM, a hydrogel with antibacterial properties that demonstrates efficacy in the treatment of bacterial cystitis. Lev@PADM is produced by combining levofloxacin with decellularized porcine acellular dermal matrix hydrogel and exhibits remarkable biocompatibility. Lev@PADM demonstrates excellent stability as a hydrogel at body temperature, enabling direct administration to the site of infection through intravesical injection. This localized delivery route circumvents the systemic circulation of levofloxacin, resulting in a swift and substantial elevation of the antimicrobial agent’s concentration specifically at the site of infection. The in vivo experimental findings provide evidence that Lev@PADM effectively prolongs the duration of levofloxacin’s action, impedes the retention and invasion of E.coli in the urinary tract, diminishes the infiltration of innate immune cells into infected tissues, and simultaneously preserves the composition of the intestinal microbiota. These results indicate that, in comparison to the exclusive administration of levofloxacin, Lev@PADM offers notable benefits in terms of preserving the integrity of the bladder epithelial barrier and suppressing the recurrence of urinary tract infections.Graphical

The bacterial culture of urine relevance in the complex treatment of incontinence in dogs

To date in Russian federation there is widespread in veterinary medicine to empiric prescription of broad-spectrum antibacterial drugs in the treatment of bacterial cystitis in dogs. The main danger of this approach is associated with the provocation of the development of antibiotic resistance of microorganisms, with the surgical treatment of animals in the active stage of the inflammatory process and associated complications, with the development of ascending infections of the urinary system. Very important for a positive clinical result in the treatment of dogs with urinary incontinence against the background of ureteral ectopia or urethral sphincter insufficiency has a compliance with the preanalytical rules when taking biomaterial (urine) for bacteriological examination by pyelocentesis or cystocentesis. So there is data how to obtaining a biomaterial and its laboratory research in this article. This article presents arguments to the feasibility and necessity of conducting a laboratory study of the bacterial composition of urine in the treatment of inflammatory diseases of the urinary system associated with urinary incontinence. This approach makes it possible to prevent the development of antibiotic resistance in bacteria, stop the actual infectious process and ensure high rates of treatment. Вacterial culture of urine is one of the most important tests to ensure the successful treatment of patients with such diseases. Also in analyzes results we can see the insufficiency and associated risks of broadspectrum antibacterial drugs’s "blind" prescription, which has negative affect for treatment

Effect of polysaccharides from seeds of Vaccaria segetalis in alleviating urinary tract infection induced bladder injury by inhibiting NLRP3 inflammasome

To study the mechanism of polysaccharides from seeds of Vaccaria segetalis( PSV) in the treatment of bacterial cystitis through the NLRP3 inflammasome pathway. The rat model of urinary tract infection was used and treated with PSV,and the urine and bladders were collected. The level of interleukin-10( IL-10) in rat urine was detected by enzyme linked immunosorbent assay( ELISA). Western blot and immunofluorescence staining were used to detect the expressions of sonic hedgehog( SHH) and NLRP3 inflammasome [NOD-like receptor thermoprotein domain 3( NLRP3),apoptosis associated speck like protein( ASC) and pro-caspase-1]. The expression of Toll-like receptor pathway was detected by RT-PCR. The death of 5637 cells induced by uropathogenic Escherichia coli( UPEC) and lactate dehydrogenase( LDH) release were evaluated using live/dead staining. The results showed that in the rat bladder,the expressions of SHH,NLRP3 inflammasomes and Toll-like receptors were significantly up-regulated,and NLRP3 inflammasomes were significantly activated by UPEC infection. The administration with PSV could significantly increase the concentration of IL-10 in urine,inhibit the expressions of SHH,NLRP3 inflammasomes and Toll-like receptors in bladder,and inhibit the activation of NLRP3 inflammasomes. A large number of 5637 cells were dead after UPEC infection and caused LDH production. PSV could significantly inhibit the death of 5637 cells and the release of LDH. In conclusion,PSV could inhibit the expression and activation of NLRP3 inflammasomes by inhibiting the Toll-like receptor pathway,thereby mitigating the bladder injury.

Commentary: Using antibiograms to promote antimicrobial stewardship during treatment of bacterial cystitis and superficial bacterial folliculitis in companion animal practice.

Commentary: Using antibiograms to promote antimicrobial stewardship during treatment of bacterial cystitis and superficial bacterial folliculitis in companion animal practice.

The role of an herbal agent in treatment for Escherichia coli induced bacterial cyctitis in rats.

The aim of this study is to evaluate the effects of the herbal agent in the prevention and treatment of bacterial cystitis in a rat model. A total of twenty-eight male Sprague- Dawley rats were divided into four groups. Group-1 constituted the control group (operated and normal saline injected into the bladder, received only drinking water for 7 days); Group-2 constituted the no-treatment group (operated, E.coli J96 strain injected into the bladder, received only drinking water for 7 days); Group-3 constituted the short-term treatment (operated, E.coli J96 strain injected into the bladder, received the herbal agent added into drinking water for 7 days) and Group-4 constituted the long-term treatment (operated, E. coli J96 strain injected into the bladder, received herbal agent added into drinking water for 14 days). At the end of the pre-defined treatment periods of duration, the rats were sacrificed, urine samples collected from the bladder for culture and bladders were harvested for histopathological evaluation. Urine culture results and histopathological findings were comparatively evaluated between the groups. Urine cultures were positive for implanted E. coli strains in 0%, 85.7%, 42.8% and 0% of rats in Group 1, Group 2, Group 3 and Group 4, respectively (p = 0.001). Although histopathological evaluation revealed increased vascular dilation in the bladder specimens obtained from Group 2 and Group 3 (p = 0.028) no significant difference was noticed in level of inflammation (p = 0.610), edema (p = 0.754) and thickness of uroepithelium (p = 0.138). While long term (14 days) treatment with an herbal agent added into the drinking water resulted in complete clearance of urine from E. coli; shorter application of the agent revealed partial clearance. Further clinical studies are needed to support our results.

Intravesical hyaluronic acid treatment improves bacterial cystitis and reduces cystitis-induced hypercontractility in rats.

To investigate the effect of intravesical hyaluronic acid on Escherichia coli-induced cystitis and cystitis-induced hypercontractility in rats. Bacterial cystitis was induced in Wistar female rats by intravesical inoculation of E. coli. Isotonic saline was instilled in the control group (n = 6). The rats were either non-treated, treated with gentamycin (4 mg/kg, 5 days) or treated intravesically with hyaluronic acid (0.5 mL, 0.5%). On the eighth day, the bladder tissues were excised for histological examination, and the measurements of myeloperoxidase, superoxide dismutase and catalase activities. Contraction/relaxation responses to carbachol, isoprotrenol and papaverine were studied. Tissue myeloperoxidase activity was increased, but superoxide dismutase and catalase activities were decreased in bacterial cystitis, while hyaluronic acid treatment reversed these changes. In the hyaluronic acid-treated group, healing of the uroepithelium was observed, while decreased inflammatory cell infiltration was obvious in gentamycin-treated group. E. coli-induced cystitis in all rats resulted in increased contraction responses to carbachol compared with controls (P < 0.01). Treatment with hyaluronic acid, but not gentamycin, significantly (P < 0.05) depressed hypercontractility at maximum carbachol concentrations. In all rats with cystitis, papaverine-induced relaxation was increased, whereas isoproterenol-induced relaxation curves were not different between the studied groups. Gentamycin treatment, despite its ameliorative effect on inflammation, had no impact on the contractile dysfunction of the injured bladder. Intravesical hyaluronic acid, in addition to its supportive role in the healing of the epithelium, seems to lower the increased threshold for contraction and to reduce oxidative stress. These findings support a potential role for hyaluronic acid in the treatment of bacterial cystitis.

Interaction between bacteria and the lumenal bladder surface: modulation by pentosan polysulfate, an experimental and theoretical approach with clinical implication.

An attempt was made to interpret bacterial adsorption to the lumenal surface of the urinary bladder wall under normal and pathological conditions according to the DLVO theory of lyophobic colloid stability, which describes the interaction between a bacterium and the bladder-wall surfaces as a balance of attraction and repulsion forces. Computer modeling suggested that a decrease in the surface potential of the bladder wall may well explain an increased bacterial adsorption, possibly associated with bacterial cystitis. With the intent of preventing bacterial adsorption, treatment of bacterial cystitis by intravesical instillation of pentosan polysulfate (PPS) was evaluated. PPS is a polysaccharide with high affinity (4 +/- 2 mg/bladder) to the bladder. The attachment of PPS strongly depends on the intrinsic properties of the bacterial surface. Theoretical considerations indicate that either complete coverage of the bacterium with PPS or an absence of PPS affinity is a prerequisite for obtaining steric interaction or prevention of bacterial sorption. Experimentally, an absence of PPS affinity (0-0.7 microgram/mg bacteria) was found for bacteria commonly found during cystitis. Immunological treatment of superficial bladder cancer by bacillus Calmette-Guérin (BCG) depends on the interaction of BCG with the bladder wall. Improvement of the treatment may be obtained by increasing BCG adsorption. In this respect, the phenomenon of bridging in which PPS binds simultaneously to both BCG and the bladder-wall surface was investigated. Theoretical considerations and experimental results appeared to be in good agreement. It was found that BCG binds a considerable amount of PPS (3.4 +/- 0.3 microgram/mg BCG). In a guinea pig model the theoretical considerations, indicating the occurrence of bridging at a low and narrow range of PPS concentrations, seemed to be confirmed. In contrast to a high PPS concentration of 10 mg/ml, at a low (0.1 mg/ml) PPS concentration a significant stimulation of the BCG-associated immune reaction(s) was observed. The results suggest that to obtain PPS-induced bridging between BCG and the bladder wall and to prevent steric interaction, PPS should be instilled prior to BCG, separated by extensive washout of free PPS.

Studies on the emergence of resistance to lomefloxacin in vitro

The emergence of resistance to lomefloxacin, norfloxacin and ciprofloxacin was investigated in nalidixic acid sensitive and resistant urinary isolates by continuous turbidimetry. A decline in susceptibility was observed after a single exposure to each of the drugs, and further increments of resistance occurred during three sequential passages. Variants resistant to one quinolone were cross-resistant to the others. The level of resistance selected by norfloxacin in three of the five test strains was greater than that observed with lomefloxacin or ciprofloxacin. In experiments in a model of the treatment of bacterial cystitis, concentrations of lomefloxacin well within those readily achievable in urine suppressed growth of nalidixic acid sensitive and resistant strains for more than 20 h without causing any decline in susceptibility of surviving bacteria.

The response of Streptococcus faecalis to ciprofloxacin, norfloxacin and enoxacin.

The response to three quinolones of a clinical isolate of Streptococcus faecalis was studied by continuous turbidimetric monitoring, by viable counting, and in an in-vitro model of the treatment of bacterial cystitis. Dense populations (c. 8 x 10(6) cfu/ml) responded to ciprofloxacin, norfloxacin and enoxacin at concentrations below the conventionally determined MIC, but variants, shown to exhibit decreased susceptibility, emerged during overnight incubation. The variants were cross-resistant to each of the three quinolones, but the resistance was lost on subculture in drug-free broth. At a concentration of ten-fold MIC, ciprofloxacin was more bactericidal than norfloxacin or enoxacin. In experiments in the bladder model, doses of ciprofloxacin achieving a peak concentration of 10, 50 or 250 mg/l suppressed bacterial growth for 20 h or more. The doses of norfloxacin or enoxacin required to achieve a comparable effect were higher than those of ciprofloxacin. A reduction in susceptibility, as judged by comparative disc testing, occurred after two cycles of exposure to norfloxacin or enoxacin in experiments in which the peak concentration achieved was 50 mg/l, but not when the peak was 250 mg/l. Reduced susceptibility to ciprofloxacin developed only in experiments in which a lower peak concentration of 10 mg/l was achieved.

Activity of fosmidomycin in an in vitro model of the treatment of bacterial cystitis.

The response to fosmidomycin of four strains of Escherichia coli was studied in an in vitro model of the treatment of bacterial cystitis. Three susceptible strains of E. coli responded well to relatively low concentrations of fosmidomycin: doses achieving peak concentrations of 50 or 250 mg/l suppressed bacterial growth for 13 h or more; however, when the surviving bacteria were challenged with a second dose, a reduced response was observed. When a fully resistant strain was exposed to fosmidomycin, bacterial growth was also suppressed for 13 h or more, even when the peak concentration achieved was below the conventionally determined minimum inhibitory concentration. Resistant variants which emerged after exposure to fosmidomycin were also resistant to fosfomycin in the absence of the potentiating agent, glucose-6-phosphate. In the presence of glucose-6-phosphate, complete (or partial) susceptibility to fosmidomycin and fosfomycin was retained by three of the four strains. These results suggest that fosmidomycin and fosfomycin are transported into E. coli by a similar mechanism, and that deletion of the hexose phosphate transport system does not occur following exposure to fosmidomycin in the absence of glucose-6-phosphate.

Correlation between bactericidal activity of fosfomycin trometamol in an in vitro model of the urinary bladder and susceptibility testing.

The present study was undertaken to define an interpretative guideline for disk diffusion susceptibility testing with fosfomycin trometamol, a new antimicrobial agent which has been developed for the treatment of urinary tract infections. Two potencies of fosfomycin disk were used: 50 and 200 micrograms, prepared in the presence and absence of glucose-6-phosphate. To verify the reliability of the results obtained in susceptibility testing, we have also evaluated the bactericidal activity of fosfomycin trometamol versus sensitive and resistant strains in an 'in vitro' model simulating the hydrokinetic aspects involved in the treatment of bacterial cystitis. The data obtained evidenced the role of glucose-6-phosphate in antimicrobial susceptibility tests as well as the importance of the urinary antibiotic concentrations to define sensitive and resistant bacteria. On the basis of our results, we recommend that a 200-microgram disk of fosfomycin containing 50 micrograms of glucose-6-phosphate should be used in antimicrobial susceptibility testing with fosfomycin trometamol.

The trometamol salt of fosfomycin: microbiological evaluation.

The spectrum of activity of fosfomycin and its pharmacological behaviour make it an attractive candidate for the oral treatment of uncomplicated urinary tract infection. Various factors affect the antibacterial activity so that results in different culture media vary widely. The highest activity was displayed in Eugonbroth and such results correlated well with those obtained in pooled human urine. The activity was enhanced in acid conditions such as commonly exist in infected urine. Glucose-6-phosphate potentiated the activity of fosfomycin against Escherichia coli and some other bacteria when tested in Eugonbroth (but less predictably in human urine) and the potentiating effect may be necessary in order to obtain therapeutically meaningful results in susceptibility tests. Experiments in an in vitro model of the treatment of bacterial cystitis (carried out in the absence of glucose-6-phosphate) indicated that both sensitive and 'resistant' strains of E. coli respond to concentrations of fosfomycin achievable by high-dose oral therapy with the trometamol salt. Resistance did not emerge in previously sensitive strains (or in one of the 2 'resistant' strains), providing a high peak level of antibiotic was achieved.

Activity of the trometamol salt of fosfomycin in an in vitro model of the treatment of bacterial cystitis.

The response to trometamol fosfomycin of four strains of Escherichia coli was studied in an in vitro model in which the hydrokinetic aspects of the treatment of bacterial cystitis can be stimulated. Two strains of E. coli that were fully susceptible to fosfomycin, and a strain of intermediate susceptibility responded well to relatively low concentrations of the trometamol salt: doses achieving peak concentrations of 50 or 250 mg/l suppressed bacterial growth for at least 18 h; however, the emergence of resistance was completely suppressed only when a peak concentration of 2500 mg/l was achieved in the bladder model. A strain of E. coli that was fully resistant to fosfomycin in conventional minimum inhibitory concentration titrations responded to the highest dosage used, but this did not prevent further resistance from emerging. These results were obtained in the absence of the potentiating agent, glucose-6-phosphate, which is commonly used in susceptibility tests of fosfomycin. The implications of the results for fosfomycin dosage in bacterial cystitis and for the interpretation of susceptibility tests is discussed.

An in-vitro model simulating the hydrokinetic aspects of the treatment of bacterial cystitis.

Various applications of an in-vitro model that simulates the hydrokinetic features of the treatment of bacterial cystitis are described. Results obtained correlate well with clinical observations, suggesting that the model has relevance in the elucidation of clinical problems.

Norfloxacin: activity against urinary tract pathogens and factors influencing the emergence of resistance.

The activity of norfloxacin was investigated in vitro in conventional minimum inhibitory concentration tests, by continuous turbidimetry and in a mechanical model simulating the hydrokinetic conditions that exist in the treatment of bacterial cystitis. The high activity of norfloxacin against virtually all bacterial pathogens isolated from infected urine was confirmed. However, in urine agar (pH 6 X 5) and in DST agar adjusted to pH 5 X 5, the activity was substantially reduced. Turbidimetric experiments indicated that increases in resistance to norfloxacin could be induced easily by sequential subculture, but results obtained in the bladder model, where conditions of exposure more closely resemble those that exist during the treatment of infection, suggest that such resistance is unlikely to arise commonly during treatment.

The assessment of antimicrobial activity in an in-vitro model of the treatment of bacterial cystitis.

In order to investigate the comparative activity of agents of the nalidixic acid series, cultures of nalidixic acid sensitive strains of E. coli were exposed to the drugs in an in-vitro model that simulates the hydrokinetic aspects of the treatment of bacterial cystitis. Intrinsic activity, as judged by the response to a single dose of drug and resistance as judged by response to a repeat dose, were investigated. All seven compounds tested in this way were able to inhibit bacterial growth for considerable periods of time even when the peak concentration achieved was as low as 10 mg/l. However, resistance emerged readily, particularly to nalidixic acid, pipemidic acid and piromidic acid. Norfloxacin was the most active of the seven compounds tested and was the only one to which resistance did not emerge at the concentrations tested. However, when two nalidixic acid resistant strains were tested in the bladder model, norfloxacin resistance was observed to emerge with one strain, but not with the other.

An in vitro evaluation of clavulanic acid, a potent, broad-spectrum β-lactamase inhibitor

The in vitro efficacy of clavulanic acid, a new broad-spectrum inhibitor of enterobacterial beta-lactamases, was investigated. In conventional agar dilution tests, the presence of a sub-inhibitory level of clavulanic acid (8 microgram/ml) lowered the minimum inhibitory concentration of ampicillin for many resistant enterobacteria to therapeutically achievable levels. When tested against dense populations of Escherichia coli and klebsiella strains in a static turbidimetric system and in an in vitro model of the treatment of bacterial cystitis, clavulanic acid plus ampicillin suppressed bacterial growth for periods far exceeding the normal interdose interval at concentrations at which neither agent alone was effective. In addition to its activity as a beta-lactamase inhibitor, clavulanic acid may interact with other beta-lactam antibiotics in a second, distinct way. Because of this synergic interactions may occur with non-beta-lactamase producing organisms, and the overall synergic effect obtained with beta-lactamase producers may be compounded of two separate elements.

The in vitro activity of ceftezol (demethylcefazolin) against dense populations of Escherichia coli.

The activity of ceftezol was examined by continuous turbidimetric monitoring of dense populations of Escherichia coli exposed to the drug. Although ceftezol was found to be very active against strains of E. coli, its activity was consistently less than that of the closely related antibiotics, cefazolin. This difference was also found when strains of E. coli were examined in a dynamic system which simulates some of the conditions in which bacteria and drug interact in the treatment of bacterial cystitis. Evidence is presented that the difference in activity between the two cephalosporins resides in a differential ability to induce certain morphological changes in E. coli and in a differential rate of destruction by escherichial beta-lactamases.