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Despite global concern about antibiotic related complications the duration of antibiotic therapy at percutaneous nephrolithotomy varies based on individual physician practice. We evaluated perioperative antibiotic related complications in patients who received extended antimicrobial therapy at percutaneous nephrolithotomy.We reviewed the records of 227 consecutive patients treated with percutaneous nephrolithotomy from 2009 to 2013. Patients with positive urine or stone cultures received extended antimicrobial treatment. All others received 7 days of empirical therapy preoperatively and postoperatively. Adverse antibiotic related events were recorded for up to 3 months.The median duration of antibiotic therapy was 14 days (IQR 14-34). Perioperatively 143 (63%), 67 (30%), 75 (33%) and 41 patients (18%) received nitrofurantoin, trimethoprim/sulfamethoxazole, fluoroquinolones and other antibiotics, respectively. Antibiotic related complications developed in 23 patients (10%) at a median of 12 days (IQR 8-19). Common complications included rash in 7 cases (3%), gastrointestinal upset in 6 (3%) and Clostridium difficile colitis in 1 (0.4%). Trimethoprim/sulfamethoxazole was associated with an increased likelihood of an adverse event (p = 0.04) but patient age, gender, and therapy type (therapeutic vs prophylactic) and duration were not. Finally, antibiotic and multidrug resistance developed in 4 (36%) and 3 patients (27%), respectively, who experienced a urinary tract infection.We report a low rate of adverse antibiotic related events in patients treated with percutaneous nephrolithotomy who received extended perioperative antibiotic therapy. Exposure to trimethoprim/sulfamethoxazole was the only identifiable risk factor for a complication. These findings should be considered when counseling patients on the risks of perioperative antimicrobial therapy at percutaneous nephrolithotomy.

INTRODUCTION AND OBJECTIVES: The appearance of extended-spectrum beta-lactamase (ESBL)-producing gram negative bacteria in urinary tract infections (UTIs) constitutes an important therapeutic challenge. The aim of this study was to describe drug susceptibility profiles of (ESBL)-producing gram-negative isolates recovered from urine samples. We also determined the antimicrobial coresistance to several agents, including fosfomycin METHODS: Retrospective analysis of 29,584 urine culture results obtained during January 2008 to December 2013 at Chonnam National Hwasun Hospital in Korea was done. The computerized database was used to identify ESBL-positive urine samples. A total of 869 ESBL positive strains were identified during the study period. We analyzed E. coli and Klebsiella isolates obtained from urine cultures and duplicate isolates; and no fosfomycin tests were excluded. The cases were further categorized according to UTI definition [community acquired (CA) UTI, health care-associated (HCA) UTI and hospital acquired (HA) UTI] and urology sample. ESBLisolates were stratified according their origin into two groups: Urology and non-Urology isolates RESULTS: Antimicrobial susceptibilities of the strains for fosfomycin were tested in 277 ESBL-positive strains: 217 ESBL-EC and 60 ESBL-KP. The most effective agents were carbapenem, such as imipenem and meropenem. The least active substances were ciprofloxacin (20.7%), Levofloxacin (22.7%), Trimethoprim-sulfamethoxazole (34.3%), and ampicillin-clavulanate (42.9 %). Overall, 243/277 (87.7%) of the isolates tested were susceptible to fosfomycin tromethamine. Higher fosfomycin sensitivity in E. coli (94.9%) were observed compared to Klebsiella (61.7%) (p1⁄40.001). ESBL-positive isolates from urological (68 isolates) and nonurological patients (209 isolates) showed similar susceptibility profiles. Except for carbapenem, CA-UTI showed higher sensitivity to fosfomycin (100%) and nitrofurantoin (93.1%), HCA-UTI showed higher sensitivity to amikacin (94.1%) and HA-UTI showed an overall poor sensitivity to antibiotics. CONCLUSIONS: Fosfomycin could be an alternative treatment option for UTIs related to ESBL-producing E. coli spp. and CA-UTI, but not for ESBL-producing Klebsiella spp. Antimicrobial susceptibilities in ESBL producing UTI was different to UTI classification. Fosfomycin showed decreased sensitivity in HCA-UTI and HA-UTI.

An understanding of the microbial origin of infectious diseases and the introduction of antimicrobial therapy stimulated more advances in the management of urinary tract infections (UTIs) in the 20th century than had occurred in the previous 5 centuries.Numerous resources were used to collect the information described in this review. Medical texts from the 19th and 20th century contain information regarding the traditional contemporary treatment of UTI during those eras. Early volumes of the Journal of Urology from the beginning of the 20th century describe the first attempts at chemotherapy for UTI. MEDLINE searches were used to collect appropriate information after 1969. Modern medical journals and modern medical texts were used to collect information on antimicrobial therapy since the late 1960s through today.Numerous advances in the diagnosis and management of UTI were made during the 20th century. Advances in microbiological and chemical assays have facilitated the development of historical uroscopy into modern day urinalysis and culture techniques, which are the cornerstone of UTI diagnosis. Imaging technologies, including x-ray, ultrasound, nuclear imaging, magnetic resonance and computerized tomography, have been particularly helpful in the diagnosis of complicated or recurrent UTIs. Major innovations in nonpharmacological therapy include noninvasive shock wave lithotripsy and percutaneous drainage of kidney abscesses. The most profound advance in UTI management during the 20th century was the discovery of antimicrobial agents. Nitrofurantoin was the first truly effective and safe antimicrobial therapy for UTI but its spectrum of activity is limited. Broad use of amoxicillin (and other beta-lactams) after its introduction in the 1970s led to the development of resistance to this antimicrobial, prompting a gradual change to trimethoprim/sulfamethoxazole (TMP/SMX) as first line therapy for UTI. However, wide use of TMP/SMX also resulted in the progressive emergence of resistance, limiting the clinical usefulness of this therapy in the modern management of UTI. Fluoroquinolones offer an attractive alternative to TMP/SMX, and American and European guidelines recommend their empirical use in areas where TMP/SMX resistance is 10% or higher.The development of antimicrobial therapy was the defining moment of 20th century medicine and one of the key innovations in medical history. While the initial promise of antimicrobials has been validated in clinical practice, overuse of certain agents has led to the emergence of resistance, illustrating the importance of using evidence based strategies to select therapy.

Summary Nitrofurantoin is commonly used for the treatment and prophylaxis of recurrent urinary tract infections (UTIs). Although relatively rare, nitrofurantoin is one of the commonest causes of drug-induced pulmonary disease, which can be potentially serious and even fatal. Knowledge of such potential adverse effects is essential to enable early recognition and withdrawal of the drug. Patients on long-term nitrofurantoin should be reviewed and monitored regularly. Management involves early consideration of the condition, and prompt withdrawal of the drug. We report three cases of nitrofurantoin-induced lung disease in patients who were on long-term nitrofurantoin for UTI prophylaxis and present a brief review of the literature on this subject.

Many antibiotics have been shown to have adverse effects on spermatogenesis. Deoxyribonucleic acid (DNA) flow cytometry of testicular aspirate has been shown to be an effective method of quantitatively evaluating testicular function. To assess this problem, DNA flow cytometry of testicular aspirate was performed on 8 groups of rats, each of which received antibiotics via daily gavage for 10 days. Aspirations were performed on days 0, 11 and 56. Data thus obtained were analyzed using a two-way ANOVA with repeated measures. Antibiotics studies included ciprofloxacin 15 mg./kg./day, sulfamethoxazole (SMX) 20 mg./kg./day (with trimethoprim (TMP) 4 mg./kg./day), nitrofurantoin 7 mg./kg./day, ofloxacin 10 mg./kg./day, lomefloxacin 6 mg./kg./day, doxycycline 3 mg./kg./day and norfloxacin 10 mg./kg./day. One group received the same SMX/TMP dose, together with folate 0.014 mg./kg./day. A statistically significant change in aspirate content on day 11 as compared with baseline existed in groups receiving TMP/SMX (p = 0.00025), nitrofurantoin (p = 0.0000043), ofloxacin (p = 0.000075) and doxycycline (p = 4.89 X 10(-9). Control rats and the group receiving TMP/SMX with folate showed no significant change. On day 56 the abnormality persisted in groups TMP/SMX (p = 0.042), nitrofurantoin (p = 0.001), ofloxacin (p = 0.036) and doxycycline (p = 0.003). Controls and groups receiving ciprofloxacin, norfloxacin and lomefloxacin continued to show no statistically significant difference from baseline on day 56. These data suggest that SMX/TMP, nitrofurantoin, ofloxacin and doxycycline significantly alter spermatogenesis. Ciprofloxacin, norfloxacin and lomefloxacin had no apparent effect on spermatogenesis as measured by DNA flow cytometry.

Objective To determine the sensitivity of 4 strains of Oxalobacter formigenes (Oxf) found in humans—HC1, Va3, CC13, and OxK—to varying concentrations of commonly prescribed antibiotics. Oxf gut colonization has been associated with a decreased risk of forming recurrent calcium oxalate kidney stones. Methods For each strain and each antibiotic concentration, 100 μL of an overnight culture and 100 μL of the appropriate antibiotic were added to a 7-mL vial of oxalate culture medium containing 20 mM oxalate. On the fourth day, vials were visually examined for growth, and a calcium oxalate precipitation test was performed to determine whether Oxf grew in the presence of the antibiotic. Results All 4 Oxf strains were resistant to amoxicillin, amoxicillin/clavulanate, ceftriaxone, cephalexin, and vancomycin, and they were all sensitive to azithromycin, ciprofloxacin, clarithromycin, clindamycin, doxycycline, gentamicin, levofloxacin, metronidazole, and tetracycline. One strain, CC13, was resistant to nitrofurantoin, and the others were sensitive. Differences in minimum inhibitory concentration between strains were demonstrated. Conclusion Four human strains of Oxf are sensitive to a number of antibiotics commonly used in clinical practice; however, minimum inhibitory concentrations differ between strains.

A 33-year-old woman received a cadaveric renal transplant for focal segmental glomerulosclerosis. Nitrofurantoin urinary prophylaxis was started on postoperative day 13 but coughing and mild hemoptysis began 2 days later. Diffuse infiltrates and worsening hemoptysis led to intubation and open lung biopsy. Clinical course, culture results and pathological evaluation excluded infectious etiologies and were consistent with a drug reaction. The case is described, and the literature on the nitrofurantoin pulmonary toxicity syndromes and pathophysiology is reviewed.

Escherichia coli and the antimicrobial pressure exerted on this microorganism can be modulated by factors dependent on the host. In this paper, we describe the distribution of antimicrobial resistance to amikacin, tobramycin, ampicillin, amoxicillin clavulanate, cefuroxime, cefoxitin, cefotaxime, imipenem, ciprofloxacin, fosfomycin, nitrofurantoin, and trimetoprim-sulfametoxazole in more than 100,000 E. coli isolates according to culture site and patient age, gender, and location. Bayesian inference was planned in all statistical analysis, and Markov chain Monte Carlo simulation was employed to estimate the model parameters. Our findings show the existence of a marked difference in the susceptibility to several antimicrobial agents depending on from where E. coli was isolated, with higher levels of resistance in isolates from medical devices, the respiratory system, and the skin and soft tissues; a higher resistance percentage in men than in women; and the existence of a clear difference in antimicrobial resistance with an age influence that cannot be explained merely by means of an increase of resistance after exposure to antimicrobials. Both men and women show increases in resistance with age, but while women show constant levels of resistance or slight increases during childbearing age and greater increases in the premenopausal age, men show a marked increase in resistance in the pubertal age. In conclusion, an overwhelming amount of data reveals the great adaptation capacity of E. coli and its close interaction with the host. Sex, age, and the origin of infection are determining factors with the ability to modulate antimicrobial resistances.

RESULTS: We identified 7,100 and 9,985 positive urine cultures performed in 1997 and 2007, respectively. The most common urinary organism was Escherichia coli. The number of patients with MRSA bacteriuria increased from 18 (0.3%) to 74 patients (0.8%), p

The preceding 4 articles in this issue of the Journal ask that we reexamine some old controversies, and familiarize ourselves with new ideas and techniques in the world of urological infection, a subject that most of us tend to take for granted. Each article raises interesting points with regard to the new world of corporate medicine and managed care. Gasser et a1 (page 146) discuss a prospective trial to test the efficacy of antimicrobial prophylaxis in patients undergoing transurethral surgery. Patients with preoperatively sterile urine were randomized to receive either 400 mg. oral fleroxacin once daily or placebo as long as the catheter was in place. Postoperative urinary tract infection rates were significantly lower in the fleroxacin group (3%) compared to the placebo group (23%). The authors conclude that prophylaxis in patients with sterile urine makes sense. Looking at the data, one can see that only 4 of the 8 patients with positive cultures had clinical signs of infection, and 1 of these patients was on fleroxacin. Only 1 patient had a positive blood culture. In addition, 1 of the fleroxacin treated patients had unexplained fever with negative blood and urine cultures. Would it make more sense to treat the 4 of 75 patients with signs of infection rather than treat 75 patients with a new, presumably expensive, fluoroquinolone for 2 to 3 days routinely? The issue of unexpected preoperative urinary tract infections (9 of 75 in this study) is easily addressed if urine is cultured several days before the planned operation rather than during the preceding 24 hours. We studied the use of nitrofurantoin in patients undergoing transurethral prostatectomy with preoperative sterile urine cultures.' A total of 223 patients was randomly assigned to groups receiving placebo, and 5 and 10 days of treatment. While antibiotic administration decreased the incidence of short-term postoperative bacteriuria from 24 to 12%, there was no change in the 4-week postoperative incidence of infection. No patient had a positive blood culture, and the clinical course of patients was not altered by the routine use of antibiotics in this population. Slaa et a1 used trimethoprim-sulfamethoxazole prophylactically following laser coagulation of the prostate2 but this is a special circumstance manifested by the presence of necrotic tissue after the procedure and the need for prolonged catheterization in some patients. If we elect only to treat infected patients, potentially to save money and decrease the development of future antibiotic resistance from unnecessary treatment, the issue of office microbiology arises and is addressed in the challenging article by Gillenwater and Clark (page 149). This important study demonstrates beyond a reasonable doubt that tentative direct disk antibiotic susceptibility in bacteriuria provides comparable results 24 hours sooner compared to standard techniques. The article confronts a politicized issue in which the hidden agenda seems to be to prevent physicians from performing urine culture and sensitivity testing in their offices. Avoiding unnecessary antibiotics and choosing the proper, specific antibiotic depend on the availability, cost and timeliness of culture and sensitivity data. As Hodgson et al recently noted, the pace of emergence of resistant microorganisms has outstripped the rate of discovery of new antibioti~s.3 The last major antibiotic class, the carbapenems, is more than 20 years old. A decade may elapse before we can expect new approaches in infection treatment to become generally available. Pleas for the judicious use

ria into bladder urine is inevitable in the course of repeated catheterization. In previous work we found bacteriuria was present in 75% of urine samples collected from children with neurogenic bladder on CIC followed for 6 months.2 In addition, pyuria was associated with bacteriuria two thirds of the time. Bacteriuria, even with pyuria, did not predict the presence of symptomatic urinary tract infection and was not associated with deterioration of the upper urinary tract during the 6 month period of study. Antimicrobial prophylaxis is commonly used in patients with chronic neurogenic bladder on CIC in an attempt to prevent bacteriuria and symptomatic infection, but the effectiveness of this strategy has not been established. A problem in investigation of the efficacy of prophylaxis is differentiation between bacteriuria and symptomatic infection. In addition, concerns about the long-term use of prophylactic antibiotics in patients with neurogenic bladder include not only drug toxicity but also the emergence of more resistant bacterial species to cause bacteriuria and infection.3

Nitrofurantoin, sulfamethizole and cephalexin peak urinary drug concentrations were studied in patients and non-human primates with unequally functioning pyelonephritic kidneys. The peak urinary drug concentration of the poorly functioning kidney in comparison to the better kidney was greater than its percentage relative blood flow or creatinine clearance but variable in its relationship to creatinine concentration, osmolality and sodium concentration. Although for each unit of creatinine clearance the poorly functioning kidney had a higher peak urinary drug concentration than the better functioning kidney, for each kidney the peak urinary drug concentration seemed to be directly proportional to the creatinine clearance, the drug dosage and the renal mechanisms of drug excretion. Nitrofurantoin in the usual recommended dosage did not reach minimal inhibitory urinary drug concentration below a unilateral creatinine clearance of 20 ml. per minute. Whereas, sulfamethizole and cephalexin reached peak urinary drug concentrations greater than the minimal inhibitory concentration at the lowest studied unilateral creatinine clearance of 4 and 11 ml. per minute, respectively.

We studied 56 sexually active premenopausal women with a normal genitourinary tract but with persistent introital colonization by enteric gram-negative bacteria who were prone to suffer recurrent urinary tract infections. Sexual intercourse was revealed as a major factor in inducing recurrent urinary tract infections, usually within 24 hours, by transferring the pre-existing introital bacteria into the bladder. Abstention from sexual activity without any additional treatment prevented the development of new urinary tract infections in these women despite persistent introital enteric bacterial flora. Urinary tract infections occurred after onset of sexual activity in all but 2 of the premenopausal women in this study. The 25 premenopausal women with recurrent urinary tract infections were subjected to early postcoital prophylaxis consisting of bladder voiding and the administration of a single tablet of either cotrimoxazole (80 mg. trimethoprim plus 400 mg. sulfamethoxazole), nalidixic acid (500 mg.), nitrofurantoin (50 or 100 mg.) or sulfonamides (500 mg. sulfisoxazole or 250 mg. sulfamethizole). Whereas 70 urinary tract infections occurred during a mean 8-month followup before treatment only 4 occurred during the mean 12.5-month followup after introduction of post-coital prophylaxis (none occurred on co-trimoxazole or nalidixic acid therapy and only 1 infection occurred on nitrofurantoin therapy). Sulfonamides are not recommended as post-coital prophylaxis because of the higher incidence of breakthrough infections. Post-coital prophylaxis with co-trimoxazole, nalidixic acid or nitrofurantoin proved to be simple, economical and efficient, and is recommended in the prevention of recurrent urinary tract infections in otherwise normal premenopausal women.

Interstitial cystitis is a pathological condition whose symptoms mimic urinary tract infection and include urgency, frequency, and moderate to severe pain. Many more women than men are affected, with antibiotic therapy being the usual first treatment approach based on symptomology. Some clinicians believe that chronic antibiotic therapy may play an etiological role in interstitial cystitis; however neither clinical nor experimental data support their opinion. The implied pathogenesis of antibiotic injury is an alteration of the bladder mucosa and its protective mucin coating to allow urine-mediated damage to the bladder wall. The purpose of this study is to evaluate rabbit urinary bladder function and morphology during chronic nitrofurantoin administration. The results demonstrate that up to twelve months of chronic nitrofurantoin administration produce no changes in 1) bacterial adherence to the rabbit bladder mucosa, 2) specific antibacterial adherence activity of the bladder mucin, and 3) ultrastructure of the mucosa, submucosa, and muscularis.

Our series of 94 cases (145 ureters) of vesicoureteral reflux is reviewed. The occasional disappearance of reflux during conservative treatment should not be mistaken for cure because of its variable nature. To avoid such a mistake voiding cystography under fluoroscopic monitoring is repeated indefinitely. Those patients who were treated surgically were followed for at least 2 to 3 years before cure was established. Transient ureteral dilatation after reimplantation was eradicated within 3 months. Postoperative urinary infection was observed at various intervals, ranging from 1 week to 5 months, and the erythrocyte sedimentation rate was likely to be influenced by infection. Postoperative chemotherapy was continued until the erythrocyte sedimentation rate was normal and there was no infection and/or dilatation of the upper tract.

Twenty-two girls with recurrent urinary tract infection and endoscopically proved cystitis cystica were studied prospectively to determine control of infection with long-term, continuous nitrofurantoin or sulfisoxazole (6 to 12 months), effect on the bladder changes and rate of recurrence of infection after discontinuation of medication. Infection was controlled equally with both drugs but, despite adequate control, 24% had evidence of cystic changes upon completion of the treatment period. An additional 44% became reinfected during the 1-year followup with no drugs. Only one-third of those presenting with urinary frequency, urgency and urge incontinence had improvement of these symptoms with control of infection alone. It appears that childhood cystitis cystica is the response of the bladder to long-term, inadequately treated bacterial lower urinary tract infection. Many months to years of continuous medication are required for healing. Toilet retraining, in addition to anticholinergics, also may be necessary to achieve urinary control.

We conducted 202 trials in 161 male hospital patients to determine if prophylactic administration of ascorbic acid or antibacterials (trimethoprim-sulfamethoxazole, nalidixic acid, methenamine hippurate or nitrofurantoin macrocrystals) would prevent bacteriuria infections in spinal cord injury patients who had had at least 1 bout of bacteriuria. None of the drugs tested appeared to be statistically effective in the doses used in preventing bacteriuria in these patients. Moreover, sensitivities were lost to several drugs other than those used prophylactically. We conclude that use of prophylactic doses of ascorbic acid or antibacterials has not proved to be beneficial in spinal cord injury patients free of indwelling catheters.

We studied and treated prospectively 62 neurologically normal children with vesicoureteral reflux using urodynamic techniques to identify uninhibited bladder contractions with voluntary sphincteric obstruction (dyssynergia). All children received antibiotic prophylaxis. Anticholinergic drugs were used additionally to treat uninhibited bladder contractions. During 6 years of followup treatment of uninhibited contractions produced a 4-fold reduction in the incidence of recurrent urinary infection and tripled the rate of reflux resolution compared to controls. These data suggest that uninhibited contractions with voluntary sphincter obstruction are an important prognostic finding in children with reflux, which when treated successfully can alter the disease course and may make surgical therapy of reflux unnecessary for some.

Chemoprophylaxis and disinfection of the operation site for the prevention of bacteriuria after a transurethral operation were assessed in controlled, prospective studies in men with sterile urine preoperatively. The majority of the control patients (65 per cent) suffered postoperative bacteriuria compared to 38.6 per cent after perioperative disinfection with Chlorhexidine and 10 per cent or less after each of 2 other regimens (intramuscular cephradine followed by oral nitrofurantoin and chlorhexidine disinfection followed by oral nitrofurantoin). The latter regimen is preferred since it avoids the use of agents with systemic action.