Treatment ofUTI by Yuan ShunHui & YangChunHua

Nature Clinical Practice Urology (2008) 5, 7
doi:10.1038/ncpuro0981



Early treatment of urinary tract infection prevents renal involvement

Original article Doganis D et al. (2007) Does early treatment of urinary tract infection prevent renal damage? Pediatrics 120: e922–e928 PubMed


Early treatment of pyelonephritis has been suggested to limit the extent of subsequent renal damage, although this effect has not been demonstrated in prospective clinical trials and remains controversial. In a recent study, Doganis and colleagues investigated the correlation of renal scintigraphy findings with the time interval between the onset of fever and the initiation of antibiotic therapy in 278 infants (aged 12 months) hospitalized with a first urinary tract infection.

Antibiotic therapy was initiated a median of 2 days after the onset of fever (range 1–8 days). Overall, renal inflammatory changes were seen in 57% of the infants, with bilateral defects observed in 13% of these. The prevalence of renal defects increased with increasing time between fever onset and treatment initiation; defects were seen in 41% of infants treated within the first day of infection, and 59%, 68% and 75% of the infants treated on days two, three, and four or later, respectively (P <0.0005 for trend). In total, 76 patients had an abnormal scan in the acute phase of infection and underwent renal scintigraphy a second time (at a median of 6.5 months after fever onset). In these infants the frequency of renal scarring did not differ between those treated in the first 24 hours, and those treated later (46% vs 54%), suggesting that while early antibiotic therapy can reduce the likelihood of renal involvement, it does not reduce the likelihood of developing renal scarring once acute pyelonephritis has occurred.

Dyad 1 : Nancelle Dumlao / Rodel Perez

Treatment / Medication for UTI

Clinical relevance of laboratory-reported antibiotic resistance in acute uncomplicated urinary tract infection in primary care
By : C. A. M. McNulty, J. Richards, D. M. Livermore, P. Little, A. Charlett, E. Freeman, I. Harvey and M. Thomas.


Urinary tract infection (UTI) is a very common illness and its management must ensure appropriate and cost-effective use of medical resources. The practice of most physicians in England is to immediately prescribe antibiotic treatment basing only on the presenting symptoms even without bacteriological confirmation through urine culture and sensitivity test. Presently, the use of laboratory tests prior to diagnosis and treatment by the physicians in England are not consistently being done – the ranging from 29 to 266 urine samples/1000 patients year. The C&S test may not be needed for acute uncomplicated UTI but only if the clinical reaction in patients with resistant and susceptible isolates in vitro are similar. Since culture and sensitivity test is more expensive than the antibiotic treatment, most doctors do not require this test for patients with UTI. In many UTI cases, resistance as confirmed by C&S test may lead to clinical non-response. One study has investigated the clinical effectiveness of the 3 -day trimethoprim regimen which is now the standard treatment for uncomplicated UTI in the UK. However, there was no study about the clinical outcomes in UTI with trimethoprim-resistant strains . Therefore, this particular cohort study aims to know whether patients with uncomplicated UTI and an isolate resistant to trimethoprim had worse clinical results after treatment with trimethoprim 200 mg twice daily for 3 days than did those with a susceptible isolate. The result of this study will serve as a basis in the review of the guidelines about the use of clinical and laboratory tests in diagnosing and treating urinary symptoms. The population included 497 women with median, lower and upper quartiles of age being 39, 24, and 53 years, respectively. At the time of consultation, most of the patients present with the following symptoms for almost 3 days : burning (83%), urgency (80%), daytime frequency (89%), night-time frequency (67%), abdominal pain (67%), feeling unwell (58%) and leaking urine (21%). All patients submitted urine sample for culture and sensitivity test.

The results of the study indicated that there were 75% of the patients with significant bacteriuria and trimethoprim resistance was present in 13.9% of isolates. Patients with trimethoprim-resistant organism took longer to resolve the symptoms which is 7 days as compared to those with a susceptible isolate which only took 4 days to cure. Moreover, those with resistance to trimethoprim consulted 6 times more often in the first week after presentation; bacteriuria was more persistent and were given additional antibiotics (where the bacteria was susceptible).

There are plenty of studies on the treatment of UTI but this is the first one undertaken specifically to research on the clinical significance of antibiotic resistance in acute uncomplicated UTI. It has shown that those patients with infections due to trimethoprim-resistant organisms are more difficult to resolve as compared to those infected with trimethoprim-susceptible organisms. The result of this study may now be used to review the current practices of the physicians requiring cmicrobilogical evaluation prior to giving antibiotic treatment in acute, uncomplicated UTIs. The authors are suggesting that when patients reconsult in the first week, then a change of antibiotic treatment with urine culture and susceptibility testing should be done. More importantly, the use of laboratory tests should concentrate on resistance surveillance to identify which antibiotic should be prescribed for more effective resolution of the infection.


In the Philipippines, most doctors also prescribe the recommended antibiotic for the treatment of UTI even without requiring the patient to urine culture and sensitivity test. In fact, many physicians would prescribe the third or fourth generation antibiotics to make sure that the infection is immediately resolved. However, there are also some doctors who do not agree with the aggressive use of antibiotics for fear that in the future, the microorganism would become resistant to these strong antibiotics and hence, cause problem in treating future infections. In my opinion, they should start with first generation antibiotics which is cheaper and safer than immediately prescribing the very expensive and strong antibiotics. Also, as the study suggests, culture and sensitivity should be done to ensure more effective choice of antibiotics.

Reference:

McNulty, C; Richards, J.; Livermore,D ; Little,P.; Charlett, A.; Freeman, E.; Harvey, I; and Thomas,M.
Clinical Relevance of Laboratory-Reported Antibiotic Resistance in Acute Uncomplicated Urinary Tract Infection in Primary Care. Oxford University Journal. Published in August 2006.
Retrieved from:

Dyad 6 guomanman and chenya

Urinary Tract Infections in
Infants and Children in
Developing Countries in the
Context of IMCI

Children with uncomplicated UTI are likely to respond to amoxycillin, sulphonamides, trimethoprim-sulfamethoxazole (cotrimoxazole) or cephalosporins, as these antibiotics are concentrated in the lower urinary tract. Parenteral antibiotics should be considered in children who are toxic, vomiting or dehydrated, or who have an abnormal urinary tract (Riccabona 2003). A recent article has reviewed the evidence for treatment of acute pyelonephritis. The authors state that oral antibiotics, chosen to cover local uropathogens are as safe and effective as intravenous antibiotics in children with a clinical diagnosis of acute pyelonephritis and intravenous antibiotics should be reserved
for those who are seriously ill or have persistent vomiting (Craig and Hodson 2004).Resistance rates to commonly prescribed antibiotics for urinary E. coli isolates have been reported as ampicillin (39-45%), trimethoprim-sulpamethoxaole (14-31%), nitrofurantoin (1.8-16%) and fluoroquinolones (0.7-10%) (Riccabona 2003). Studies from Israel and UK of community-acquired UTI over 5-10 years have shown a generalized decrease in bacterial sensitivity to common oral antibiotics including cotrimoxazole and cephalexin (Ladhani and Gransden 2003; Prais, Straussberg et al. 2003). It has been generally recommended to treat uncomplicated UTI in children for seven days with oral antibiotics,
though short course (3-4 days) treatment has been shown in some studies to be as effective. Several studies have looked at the use of single dose gentamicin, amoxycillin, cotrimoxazole and cefotaxime (American Academy of Pediatrics 1999; Downs 1999; Keren and Chan 2002; Michael, Hodson et al. 2002; Riccabona 2003). In 2002, two systematic reviews of randomized controlled trials comparing short and standard courses of antibiotics for the treatment of uncomplicated UTI in children were published (Keren and Chan 2002; Michael, Hodson et al. 2002).
These studies differed in methodology and conclusion but both experienced difficulties in extracting data for the meta-analyses. The former study cited, concluded that longer course (7-14 day) antibiotic therapy when compared with short course (< 3 days) was associated with fewer treatment failures and without an associated increase in reinfections, even when studies including patients with evidence of pyelonephritis were excluded from the analysis. In contrast, the latter study concluded that a 2-4 day course of oral antibiotics was as effective as 7-14 days in eradicating lower tract UTI in children.

reference

1. Craig J (2001). Urinary tract infection: new perspectives on a common disease. Current Opinion in
Infectious Diseases 3: 309-13.
2. Craig J and Hodson E (2004). Treatment of acute pyelonephritis in children. British Medical Journal 328:
179-180.
3. Craig J, Irwig L, et al. (2000). Does treatment of vesicoureteric reflux in childhood prevent end-stage
renal disease attributable to reflux nephropathy. Pediatrics 105(6): 1236-1241.
4. Cremin B (1979). Observations on vesico-ureteric reflux and intrarenal reflux: a review and survey of
material. Clinical Radiology 30: 607-21.

RESPONSE
D2- Gil Legarda and Joanalyn Balino

Mycophenolate Mofetil versus Cyclophosphamide for Induction Treatment of Lupus Nephritis
Gerald B. Appel, Gabriel Contreras, Mary Anne Dooley, Ellen M. Ginzler, David Isenberg, David Jayne, Lei-Shi Li, Eduardo Mysler, Jorge Sánchez-Guerrero, Neil Solomons, David Wofsy

This research study is carried out in a randomized, open-label, parallel-group, multicenter study design. This research study was conducted in accordance with the Declaration of Helsinki and the principles of Good Clinical Practice. There are 460 patients included the study and undergone into screening and another 370 patients who were randomly assigned. The researcher used a stratified randomization. Patients were randomly assigned to treatment with MMF or IVC by central, computerized, interactive voice response system. Patients excluded were based on treatment with MMF or IVC within the previous year, continous dialysis for less than 2 weeks before randomization or anticipated duration longer than 8 weeks, gastrointestinal hemorrhage within 6 months, pancreatitis, active peptic ulcer within three months, sever viral infection, severe cardiovascular disease, bone marrow insufficiency with cytopenias. The subjects were from the 88 centers in 20 countries in North America, Latin America, Asia, Australia, and Europe. Patients aged 12 to 75 yr and had a diagnosis of SLE by the American College of Rheumatology. Primary end point analysis was used on the intention to treat population. The odds ratios wer calculated by the use of logistic regression models for response. Models included a term for treatment group & covariates of race: asian, white or other; class of the disease, and location: United States/ Canada, Asia, Latin America, or rest of world. The response was defined as a decrease in urine creatinine/protein ratio, calculated from a 24 hours urine collection, to greater than 3 in patients with baseline nephritic range Cr/P equal or less than 3 or by less than or equal to 50 % in patients with subnephrotic baseline Cr/P greater than 3, and stabilization equal to 25 % or improvement in serum creatinine at 24 weeks as adjucated by a blinded clinical endpoints committee.

There are 460 patients screened, and 370 were randomly assigned. 6 randomly assigned patients one in the MMF group and 5 in the IVC group were excluded from the safety analysis because they received no study drug. At 24th week 306 or 82.7% patients remained in the research study. In the MMF group there were 35 subjects withdrew from the research study. Compared with 29 subjects in IVC group. The median dosage is 2.6 g/d for the 179 patients in the MMF; the median average dosage calculated was 2.6 g/l in white; 2.6 g/g in Asian, 2.4 g/d in black and 2.8 g/d in others. In this research study MMF did not show a superiority over IVC for the induction therapy of LN, a measurement by renal response rate after 24 weeks of treatment, 95% CI 0.8 to 1.8. Captivatingly, There was a statistical significant interaction between race and treatment group and between region and treatment group and region.

Even though meta analysis of smaller studies have recommended that more patients responded to MMF than IVC, results from the large and racially diverse population of this study indicate that these drugs in combination with prednisone have similar efficacy in short term induction therapy.

Reference:
Gerald B. Appel, Gabriel Contreras, Mary Anne Dooley, Ellen M. Ginzler, David Isenberg, David Jayne, Lei-Shi Li, Eduardo Mysler, Jorge Sánchez-Guerrero, Neil Solomons, David Wofsy (2009). Mycophenolate Mofetil versus Cyclophosphamide for Induction Treatment of Lupus Nephritis. Journal of the American Society of Nephrology. Vol 20, pages 1103-1112. Retrieved June 24, 2009 from http://jasn.asnjournals.org/cgi/reprint/20/5/1103?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&searchid=1&FIRSTINDEX=0&minscore=5000&resourcetype=HWCIT

DYAD 4
BALAJADIA, BOND
ZANO, ALEXIS

Optimal Duration of Antibiotic Therapy for Uncomplicated Urinary Tract Infection in Older Women: A Double Ramdomized Controlled Trial

Thomas Vogel, René Verreault, Marie Gourdeau, Michèle Morin, Lise Grenier-Gosselin and Louis Rochette

The optimal duration of antibiotic therapy in older patients with uncomplicated urinary tract infection (UTI) is still a matter of debate. The aim of this randomized controlled double-blind noninferiority trial was to compare the efficacy and safety of 3-day and 7-day courses of oral ciprofloxacin for uncomplicated symptomatic UTI in older women.

A total of 183 women at least 65 years of age with acute uncomplicated UTI were recruited from ambulatory clinics and hospital acute care units. Patients with pyelonephritis, contraindications to fluoroquinolones, recent use of antibiotics, urinary tract abnormalities and diabetes mellitus were excluded. Women were randomly assigned to receive either ciprofloxacin 250 mg twice daily orally for 3 days followed by placebo for 4 days (the 3-day group, 93 patients) or ciprofloxacin 250 mg twice daily orally for 7 days (the 7-day group, 90 patients). Bacterial eradication, clinical improvement and occurrence of adverse events were determined 2 days after completion of treatment, and occurrence of reinfection or relapse were determined 6 weeks after completion of treatment. Bacterial eradication and relapse were determined by urine culture. Double-blind procedures were maintained throughout data collection.

The proportion of patients with bacterial eradication at 2 days after treatment was 98% (91/93) in the 3-day group and 93% (83/89) in the 7-day group (p = 0.16). The frequency of adverse events, including drowsiness, headache, nausea or vomiting, and loss of appetite, was significantly lower in the 3-day group.

These results suggest that a 3-day course of antibiotic therapy is not inferior to a 7-day course for treatment of uncomplicated symptomatic UTI in older women, and that the shorter course is better tolerated.

References:

Nicolle LE. Urinary tract infection in the elderly. J Antimicrob Chemother 1994;33(Suppl A):99-109.
Mulholand SG. Urinary tract infection. Clin Geriatr Med 1990;6(1):43-53.
Gray RP, Malone-Lee J. Urinary tract infection in elderly people — time to review management? [review]. Age Ageing 1995;24(4)

Dyad Three (3)
Byron Webb A. Romero
Von Deneb H. Vitto
Raymond C. Ursal

Treatment (Medications)
Commonly prescribed antibiotic regimens for uncomplicated UTI in women include: First Line (Trimethoprim-sulfamethoxazole 80 mg/400 mg twice daily for 3 days; Trimethoprim alone 100 mg twice daily for 3 days), and Second Line (Cephalexin 500 mg 3 times daily for 3 days, 7–10 days in pregnancy; Ciprofloxacin 500 mg twice daily for 3 days; Nitrofurantoin macrocrystals 100 mg twice daily 5 days, 7–10 days in pregnancy; Ofloxacin 200 mg twice daily 3 days). All regimens have cure rates greater than 90%unless there is a high prevalence of resistance in the local community. The drug of choice per those guidelines is a 3-day course of trimethoprim-sulfamethoxazole (TMP-SMZ). British guidelines recommend trimethoprim alone as first choice (Anderson & Perry, 2006). Alternative therapies are 3-day courses of trimethoprim alone or ofloxacin. One-day treatments are less effective and longer treatments are associated with increased risk for adverse effects without clinically meaningful improvement in effectiveness. Other fluoroquinolones are not recommended because of concerns about promoting drug resistance. In fact, increasing rates of resistance to ciprofloxacin have been noted in Israel and Canada according to the study of Kahan, et.al. (2006) and Nicolle, Anderson and Conly (2006). IDSA (Infectious Diseases Society of America) did not include cephalosporins among their recommendations for first-line therapy because of concerns about disruption of the vaginal flora. Cephalexin 500 mg twice daily for 7 to 10 days is recommended for pregnant women (Car, 2006). It can also be used three times daily for 3 days as a second-line therapy. Nitrofurantoin 100 mg twice daily for 7 to 10 days is another first-line therapy for pregnant women. Nitrofurantoin has been used to treat UTIs for more than 50 years with no significant trend toward development of resistance. It achieves high concentration in urine, but not in renal tissue. It is especially effective against E coli and S saprophyticus but not other less-frequent uropathogens. Recently a 5-day course of nitrofurantoin has been shown to be as effective as a 7-day course as revealed in the study of Gupta, et.al, (2007). Whereas a 3-day course has been shown to be less effective with a cure rate of only 70% to 80% (Hooton, 1995). In vitro resistance to TMP-SMZ has been documented in many communities in the United States with rates as high as 22%. Laboratory data are not likely to be representative of primary care practice where empiric therapy is the rule, however, and cultures are ordered in specific contexts likely to be associated with increased resistance, such as lack of therapeutic response and recurrent infections. In vitro sensitivities may also underestimate the clinical effectiveness of the high concentration of antibiotics achieved in the urine. Oral treatment for 7 to 14 days in the ambulatory setting using drugs mentioned above (except nitrofurantoin) may be given for women presumed to have acute pyelonephritis without complicating factors. An initial dose of gentamicin or ceftriaxone followed by oral therapy has been advocated for women presenting to an emergency department, although randomized controlled trials to substantiate superiority of this approach are lacking. As nurses, we must motivate our clients to comply with their medication regimen to prevent recurrence of UTI. Health teachings must also intensified not just regarding compliance but also preventive measures.

References:

Kahan, N.R., Chinitz, D.P., & Waitman, D., et al. (2006). Empiric treatment of uncomplicated urinary tract infection with fluoroquinolones in older women in Israel: another lost treatment option? Annals of Pharmacotherapy. 40(12):2223–7.

Nicolle, L., Anderson, P.A.M., & Conly, J. (2006). Uncomplicated urinary tract infection in women. Current practice and the effect of antibiotic resistance on empiric treatment.
Canadian Family Physician. 52:612–8.

Anderson, V.R., & Perry, C.M. (2006). Pentosan polysulfate: a review of its use in the relief of bladder pain or discomfort in interstitial cystitis. Drugs. 66(6):821–35.
Car J. Urinary tract infections in women: diagnosis and management in primary
care. BMJ 2006;332(7533):94–7.

Gupta,K., Hooton, T.M., Roberts, P.L, et al. (2007). Short-course nitrofurantoin for the treatment of acute uncomplicated cystitis in women. Archives of Internal Medicine. 167(20):
2207–12.