Ciprofloxacin and therapy of urinary tract infections, including those due to Staphylococcus saprophyticus]

Staphylococcus saprophyticus is one of the main pathogens of cystitis in young women. The human biotopes are contaminated by the staphylococcus on direct contacts with domestic animals or after using not properly cooked food of animal origin. Young women are more susceptible to colonization of the urinary tract by S. saprophyticus vs. the other contingents. Sexual intercourse is conducive to the colonization and infection. Shifts in the urinary tract microflora due to the use of spermicide, as well as candidiasis promote colonization of the urinary tract by S. saprophyticus. At present fluoroquinolones are considered as a significant independent group of chemotherapeutics within the class of quinolones, inhibitors of DNA gyrase, characterized by high clinical efficacy in the treatment of urinary tract infections. Especially significant clinical experience with ciprofloxacin in the therapy of urinary tract infections is available.     

Characteristic features of etiology and antibiotic susceptibility of urinary tract infection pathogens in patients with diabetes mellitus]

Patients with diabetes mellitus and urinary tract infection were examined. The structure of the pathogens and their antibiotic susceptibility were investigated. Escherichia coli was shown to be the main pathogen of urinary tract infections in the patients with diabetes mellitus. The highest activity against the E. coli isolates was revealed in amoxycillin/clavulanate (92% of the susceptible strains), the 3rd and 4th generation cephalosporins, carbapenems, amikacin (100%) and fluoroquinolones (96%). At the same time the isolates were resistant to aminopenicillins and co-trimoxazole (29.3 and 16% respectively).     

New quinolones in urological diseases of an inflammatory nature]

New drugs of the group of the 3rd generation fluoroquinolones i. e. norfloxacin, ciprofloxacin, ofloxacin and pefloxacin possess a high antibacterial activity against the majority of the problem causative agents of urinary infections. This was confirmed by the studies on sensitivity of 950 clinical strains of the pathogens isolated from inpatients of an urological department. Sensitivity of the majority of the pathogens to the fluoroquinolones was the following: 80.3 to 100 per cent among enteric bacteria, 80.2 to 89.6 per cent among Pseudomonas spp. and 94.7 to 100 per cent among Staphylococci, 288 patients were treated with the fluoroquinolones. The patients were divided into 3 groups according to the urinary infection i. e. acute inflammatory diseases, chronic pyelonephritis and chronic inflammatory diseases of the genital tract. The results of the studies estimated by complex clinico-laboratory indices revealed a close efficacy of the drugs in the patients. This was due to their analogous antibacterial spectra and similar pharmacokinetic characteristics investigated in 23 patients after the drug administration by various routes: intravenous and oral. No differences in tolerance of the fluoroquinolones were observed.     

Intravaginal instillation of lactobacilli for prevention of recurrent urinary tract infections

Urinary tract infections remain a common problem, particularly in the female population. New methods are required to manage recurrent cystitis, and extensive research to date has suggested that restoration of the lactobacilli flora of the urogenital tract may prevent these infections. In this study, five females suffering from recurrent urinary tract infections were treated twice weekly with intravaginal and perineal implantation of Lactobacillus casei GR-1. These organisms colonized the epithelium and prevented the emergence of coliform bacteria in most instances, but did not appear to affect enterococcal colonization. In vitro studies showed that L. casei GR-1 inhibited the growth of the coliforms but did not inhibit enterococci. Each of the five patients had infection-free periods ranging from 4 weeks to 6 months. The treatment was well tolerated, had no side effects, led to an improved well-being, and was preferred to antibiotic treatment by all of the patients. These human studies, albeit of a limited nature, are the first to examine the potential for lactobacillus therapy in the prevention of urinary tract infections. The results show that lactobacilli therapy, using carefully selected organisms to treat patients who are closely followed, may be effective in the prevention of recurrent urinary tract infections.     

Synthetic peptide vaccine and antibody therapeutic development: prevention and treatment of Pseudomonas aeruginosa

Pseudomonas aeruginosa and Pseudomonas maltophilia account for 80% of opportunistic infections by pseudomonads. Pseudomonas aeruginosa is an opportunistic pathogen that causes urinary tract infections, respiratory system infections, dermatitis, soft tissue infections, bacteremia, and a variety of systemic infections, particularly in patients with severe burns, and in cancer and AIDS patients who are immunosuppressed. Pseudomonas aeruginosa is notable for its resistance to antibiotics, and is therefore a particularly dangerous pathogen. Only a few antibiotics are effective against Pseudomonas, including fluoroquinolones, gentamicin, and imipenem, and even these antibiotics are not effective against all strains. The difficulty treating Pseudomonas infections with antibiotics is most dramatically illustrated in cystic fibrosis patients, virtually all of whom eventually become infected with a strain that is so resistant that it cannot be treated. Since antibiotic therapy has proved so ineffective as a treatment, we embarked on a research program to investigate the development of a synthetic peptide consensus sequence vaccine for this pathogen. In this review article we will describe our work over the last 15 years to develop a synthetic peptide consensus sequence anti-adhesin vaccine and a related therapeutic monoclonal antibody (cross-reactive to multiple strains) to be used in the prevention and treatment of P. aeruginosa infections. Further, we describe the identification and isolation of a small peptide structural element found in P. aeruginosa strain K (PAK) bacterial pili, which has been proven to function as a host epithelial cell-surface receptor binding domain. Heterologous peptides are found in the pili of all strains of P. aeruginosa that have been sequenced to date. Several of these peptide sequences have been used in the development of an consensus sequence anti-adhesin vaccine targeted at the prevention of host cell attachment and further for the generation of a monoclonal antibody capable of prevention and treatment of existing infections.     

Mutations in the gyrA and parC genes associated with fluoroquinolone resistance in clinical isolates of Citrobacter freundii

We determined partial sequences of the gyrA and parC genes of Citrobacter freundii type strain, and then examined 38 C. freundii clinical strains isolated from patients with urinary tract infections for the association of alterations in GyrA and ParC with susceptibility to fluoroquinolones. Our results suggest that in C. freundii DNA gyrase may be a primary target of quinolones, that an amino acid change at Thr-83 or Asp-87 in GyrA is sufficient to decrease susceptibility to fluoroquinolones, and that accumulation of changes in GyrA with the simultaneous presence of an alteration at Ser-80 or Glu-84 in ParC may be associated with the development of high-level fluoroquinolone resistance in C. freundii clinical isolates.     

Epidemiology of symptomatic infections of the urinary tract in children.

The epidemiology of symptomatic infections of the urinary tract in children and the factors that may alter the risk of infection are not well known. Numbers of children aged under 15 discharged from hospitals because of symptomatic infections of the urinary tract during 1978-84 were obtained from the database kept by the Finnish National Board of Health. Information on continuous treatment for recurrent urinary tract infections was obtained from records kept by the Social Insurance Institution on patients receiving free medicines. The yearly rate of attacks of symptomatic infections/1000 girls decreased significantly from 2.67 (95% confidence interval 2.52 to 2.82) in 1978 to 1.88 (1.76 to 2.01) in 1984. In boys the rate also decreased significantly, from 0.85 (0.77 to 0.93) in 1978 to 0.59 (0.52 to 0.66) in 1984. The period prevalence of free treatment/1000 girls decreased significantly from 7.80 (7.55 to 8.05) in 1978 to 5.30 (5.10 to 5.51) in 1984 but did not change significantly in boys. Although the findings may partly have been caused by changes in policies of admission to hospital, they suggest a decreasing trend in symptomatic urinary tract infections in childhood, which may be associated with changes in the care of infants.     

A case of urinary tract infection due to Salmonella enterica serovar Virchow and review of the related literature

Nontyphoid salmonella (NTS) serotypes can cause gastroenteritis, bacteriemia, and focal infections. However, these focal infections, including urinary tract infections (UTI), are occasionally observed; in particular, the presence of several predisposing factors, such as immunodeficiency and structural abnormality in the urinary tract, increase the possibility of the occurrence of infection. We present a case of UTI caused by Salmonella enterica serovar Virchow in an elderly and debilitated patient with benign prostatic hyperplasia (BPH). Administration of appropriate antibiotic treatment resulted in recovery of the patient's clinical course.     

Preventive and therapeutic administration of an indigenous <Emphasis Type="Italic">Lactobacillus</Emphasis> sp. strain against <Emphasis Type="Italic">Proteus mirabilis</Emphasis> ascending urinary tract infection in a mouse model

Probiotics are increasingly being considered as non-pharmaceutical and safe potential alternatives for the treatment and prevention of a variety of pathologies including urinary tract infections. These are the most common infections in medical practice and are frequently treated with antibiotics, which have generated an intense selective pressure over bacterial populations. Proteus mirabilis is a common cause of urinary tract infections in catheterised patients and people with abnormalities of the urinary tract. In this work we isolated, identified and characterised an indigenous Lactobacillus murinus strain (LbO2) from the vaginal tract of a female mouse. In vitro characterisation of LbO2 included acid and bile salts tolerance, growth in urine, adherence to uroepithelial cells and in vitro antimicrobial activity. The selected strain showed interesting properties, suitable for its use as a probiotic. The ability of LbO2 to prevent and even treat ascending P. mirabilis urinary tract infection was assessed using an experimental model in the mouse. Kidney and bladder P. mirabilis counts were significantly lower in mice preventively treated with the probiotic than in non-treated mice. When LbO2 was used for therapeutic treatment, bladder counts of treated mice were significantly lower although no significant differences were detected in P. mirabilis kidney colonisation of treated and non-treated animals. These results are encouraging and prompt further research related to probiotic strains and the basis of their effects for their use in human and animal health.     

The role of E. coli adhesiveness in the pathogenesis and clinical course of urinary tract infections]

An infection with E. coli is the most frequent cause of the urinary infections in childhood. Virulence depends on several factors out of which a principal role is played by the adhesion of bacteria to the urinary tract epithelium. Such a property have E. coli strains with adherence mannose-positive fimbriae of type P with antigens recognizing and binding glycolipid receptors on epithelial cells in the urinary tract. Children with such infections owe their "sensitivity+" (10% of the population) to genetically determined large number o receptors binding E. coli strains. Incidence and clinical course of the urinary tract infections have been analysed in the group of 184 children. Moreover, sequelae of the urinary tract infections with E. coli have been analysed in dependence on E. coli strain characteristics, i.e. presence or absence of adherent fimbriae from cases of cystitis and significant asymptomatic bacteriuria. Considering pathogenesis of the urinary tract infections as the result of interactions between bacteria and host, antigenic properties of adherent fimbriae might be used for preparation of a vaccine preventing such infections.     

内毒素和降钙素原在妇科术后尿路感染中的鉴别诊断价值

目的评价中段尿内毒素和血清降钙素原在妇科术后不同种类细菌尿路感染中的鉴别诊断价值。方法收集临床1205例妇科术后患者中段尿进行细菌培养及内毒素检测,同时对患者进行血清降钙素原检测,比较结果对尿路感染的鉴别诊断价值。结果1205份标本中尿培养出阳性350例,感染率为29．04％,其中298例为均存在留置导尿管,而在剩余400例尿培养阴性的患者中仅仅120例留置导尿管。两组之间差异有统计学意义（χ2=26．78,P〈0．05）。其中革兰阴性杆菌189例（54％）,革兰阳性菌112例（32％）,真菌49例（14％）。在三组患者中,中段尿内毒素在革兰阴性菌引起的术后尿路感染较革兰阳性菌和真菌的患者中明显升高,差异均有统计学意义（P〈0．05）。而对于血清降钙素原在革兰阴性菌和革兰阳性菌感染的患者明显高于真菌尿路感染的患者,差异均有统计学意义（P〈0．05）。而在革兰阴性菌和革兰阳性菌感染的患者中差异无统计学意义（P〉0．05）。结论妇科术后尿路感染与留置导尿管密切相关,革兰阴性菌是引起妇科术后尿路感染的主要致病菌,中段尿内毒素有助于鉴别诊断出革兰阴性菌引起尿路感染,而血清PCT升高时则有助于排除真菌尿路感染。     

Ureteral stent-associated infection and sepsis: pathogenesis and prevention: a review

Ureteral stents are commonly used devices in hospital settings. However, their usage is often complicated by associated urinary tract infections as a result of bacterial adhesion onto the indwelling implant surfaces, followed by the formation of layers of biofilm. Once formed, the biofilm is exceedingly difficult to remove, potentially leading to further morbidity and even urosepsis. Urosepsis, where pathogens from the urinary tract enter the bloodstream, has a mortality rate of up to 50% of severely infected patients. Hence, it is important to understand its pathogenesis. In this review, ureteral stent-associated urinary tract infection and urosepsis will be addressed. In particular, the bacterial mechanisms involved, as well as the prevention and treatment of these infections will be discussed.     

A Clinical Trial of Cephaloridine

Cephaloridine, a cephalosporin derivative, was administered to 30 selected patients, including 19 with moderate to severe impairment of renal function. This antibiotic eradicated infections due to Staphylococcus pyogenes, and urinary tract infections due to a single member of the species Escherichia coli or Aerobacter aerogenes, which were sensitive to the drug on bacteriological testing. The drug failed in mixed urinary tract infections.No adverse effects were observed except for the development of superinfection in patients with urinary tract infections. No allergic reactions were noted in 10 patients who had reported previous reactions to penicillin.From these studies in patients with renal disease, approximations can be made concerning dose requirements in these special cases. Because of the apparent absence of dose-related toxic effects in humans, cephaloridine was particularly useful in the treatment of patients with renal disease and infections due to susceptible bacteria.     

Epidemiology of urinary tract diseases in general practice

During a one-year morbidity survey of urinary tract diseases in general practice 741 cases were diagnosed. Only about half of all the patients with symptoms of urinary tract infection had significant bacteriuria. In young women urinary tract infections and symptoms from the urinary tract without bacteriuria—in particular urethritis—were found to predominate. In middle-aged women, the urinary tract symptoms were ascribed increasingly to genital prolapse, while incidence of urolithiasis was the highest in any group, and urinary tract infections became less frequent. The prevalence of urinary tract infection showed another increase in elderly women, and recurrent/chronic pyelonephritis, which occurs with a steadily increasing prevalence throughout all age groups, became common.In younger male urological patients diseases with symptoms of urinary tract infection without bacteriuria were predominant, whereas prostatitis and urinary tract infections were less frequent. In middle-aged men, urolithiasis was especially frequent, while an increasing proportion of elderly men had prostatic hypertrophy, urinary tract infections, and recurrent/chronic pyelonephritis.     

Untreated asymptomatic bacteriuria in girls: II--Effect of phenoxymethylpenicillin and erythromycin given for intercurrent infections.

OBJECTIVE--To investigate the effects of phenoxymethylpenicillin and erythromycin on urinary isolates from patients with untreated asymptomatic bacteriuria. DESIGN--Retrospective study of subgroup of patients from cohort followed up till the end of 1986. SETTING--Outpatient clinic for children with urinary tract infections. PATIENTS--51 Girls aged under 15 with untreated asymptomatic bacteriuria. INTERVENTIONS--Before 1982 intercurrent infections (mostly tonsillitis or otitis) were treated with phenoxymethylpenicillin; after 1982 erythromycin treatment was preferred. END POINTS--Change of bacterial strain in urinary tract and symptomatic recurrences of disease. MEASUREMENTS AND MAIN RESULTS--Bacteria identified by serotype and electrophoretic type and compared before and after antibiotic treatment. Bacteriuria eradicated and replaced by new strains in most patients treated with phenoxymethylpenicillin, leading to symptomatic recurrences in about 15%. Conversely, patients given erythromycin rarely showed change in bacteriuria and none suffered symptomatic recurrence. CONCLUSIONS--In girls with untreated asymptomatic bacteriuria the use of phenoxymethylpenicillin for intercurrent infections may lead to a change of urinary bacteria and leave them at substantial risk of acute pyelonephritis. With erythromycin this risk is small (2/20 courses in this series).     

Susceptibility to antibiotics of Enterobacter spp. rods isolated from urine

Enterobacter spp. rods are opportunistic microorganisms which cause of urinary tract infections. The aim of this study was the evaluation of the susceptibility to antimicrobial agents antibiotics of Enterobacter spp. rods isolated from urine. The study was carried 50 of Enterobacter spp strains isolated in the Clinical Microbiology Department of dr. A. Jurasz University Hospital. Antibiotic susceptibility was tested by disk diffusion method. All of strains were susceptible to imipenem and meropenem. There was 87,5% of strains sensitive to doripenem, 79,2% to ertapenem, 54,0% to piperacillin/tazobactam and 50,0% to cephepime. The relatively high percentage (62,0%) of Enterobacter spp. was sensitive to fluoroquinolones. Extended spectrum beta-lactamases were produced by 24 (48,0%) strains.     

Clinical results of the treatment of bacterial infections in children with ceftazidime

Ceftazidime (Fortum-Glaxo) was administrated to 19 children with urinary tract infections and to 21 children with pneumonia. Clinical symptoms of the infections resolved in 17 children (89%) with the urinary tract infections treated with ceftazidime within 4 days. The remaining children (11%) recovered after 7 days of therapy. Clinical symptoms of pneumonia resolved in 19 children (90%) within 7 days of the treatment. A significant improvement was achieved in the remaining 2 children after 10 days of the treatment.     

Susceptibility of Pseudomonas aeruginosa Urinary Tract Isolates and Influence of Urinary Tract Conditions on Antibiotic Tolerance

Pseudomonas aeruginosa is an opportunistic human pathogen, which can cause severe urinary tract infections (UTIs). Because of the high intrinsic antibiotic resistance of P. aeruginosa and its ability to develop new resistances during antibiotic treatment, these infections are difficult to eradicate. The antibiotic susceptibility of 32 P. aeruginosa isolates from acute and chronic UTIs were analysed under standardized conditions showing 19% multi-drug resistant strains. Furthermore, the antibiotic tolerance of two P. aeruginosa strains to ciprofloxacin and tobramycin was analysed under urinary tract-relevant conditions which considered nutrient composition, biofilm growth, growth phase, and oxygen concentration. These conditions significantly enhance the antibiotic tolerance of P. aeruginosa up to 6000-fold indicating an adaptation of the bacterium to the specific conditions present in the urinary tract. This reversible phenomenon is possibly due to the increased formation of persister cells and is based on iron limitation in artificial urine. The results suggest that the general high antibiotic resistance of P. aeruginosa urinary tract isolates together with the increasing tolerance of P. aeruginosa grown under urinary tract conditions decrease the efficiency of antibiotic treatment of UTIs.     

Urinary tract infections in children. An update.

Urinary tract infection is a common and frequently recurring condition in children. The susceptibility of the host, the presence of urinary tract abnormalities, and the virulence of the urinary pathogens are of primary importance in the development of the infection. Renal parenchymal scarring, hypertension, and renal insufficiency are well-established complications of the infection in children. To reduce the risk of renal damage, diagnosis and treatment must be prompt. The diagnosis demands radiologic evaluation of the urinary tract in all boys, all children younger than 5 years, all patients with voiding dysfunction, and school-aged girls with recurrent infection to identify those patients with vesicoureteral reflux, obstruction, or other urinary tract abnormalities. Both voiding cystourethrography and renal ultrasonography are the initial examinations to use to determine the next appropriate study. Children with vesicoureteral reflux or with recurrent urinary tract infections should receive prophylactic antibiotic therapy and should be observed closely to prevent renal scarring.