Torsten Sandberg

Intake of Lactobacillus plantarum reduces certain gastrointestinal symptoms during treatment with antibiotics.

Goals To examine if intake of Lactobacillus plantarum can prevent gastrointestinal side effects in antibiotic-treated patients. Background Diarrhea is a common side effect of treatment with antibiotics. Some studies indicate that the risk of antibiotic-associated diarrhea can be reduced by administration of certain probiotic microorganisms. Study Patients treated for infections at a university hospital infectious diseases clinic were randomized to daily intake of either a fruit drink with L. plantarum 299v (1010 colony forming units/d) or a placebo drink, until a week after termination of antibiotic treatment. Subjects recorded the number and consistency of stools as well as gastrointestinal symptoms until up to 3 weeks after last intake of test drink. Fecal samples were collected before the first intake of test drink and after termination of antibiotic therapy and analyzed for Clostridium difficile toxin. Results Clinical characteristics on admission were similar in the 2 groups. The overall risk of developing loose or watery stools was significantly lower among those receiving L. plantarum [odds ratio (OR), 0.69; 95% confidence interval (CI), 0.52-0.92; P=0.012], as was development of nausea (OR, 0.51; 95% CI, 0.30-0.85; P=0.0097). Diarrhea defined as ≥3 loose stools/24 h for ≥2 consecutive days was unaffected by the treatment (OR, 1.4; 95% CI, 0.33-6.0; P=0.86). No significant differences regarding carriage of toxin producing C. difficile were observed between the groups. Conclusions Our results indicate that intake of L. plantarum could have a preventive effect on milder gastrointestinal symptoms during treatment with antibiotics.

Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomised, open-label and double-blind, placebo-controlled, non-inferiority trial

BACKGROUND Acute pyelonephritis is a common infection in adult women, but there is a paucity of controlled trials of its treatment and the optimum duration of antibiotic treatment has not been properly defined. We compared the efficacy of ciprofloxacin for 7 days and 14 days in women with community-acquired acute pyelonephritis. METHODS In a prospective, non-inferiority trial undertaken at 21 centres of infectious diseases in Sweden, women (aged ≥18 years) who were not pregnant and had a presumptive diagnosis of acute pyelonephritis were randomly assigned to oral treatment with ciprofloxacin 500 mg twice daily for 7 days or 14 days. The first week was open label. A computer-generated randomisation list in block sizes of two was used for treatment allocation in a 1:1 ratio. The study was double-blind and placebo-controlled during the second week of treatment, which was either continuation of ciprofloxacin 500 mg or placebo tablets twice daily according to the randomisation code. Patients, carers, site investigators, and trial coordinating centre staff were masked to group assignment. The primary endpoint was the clinical and bacteriological outcome 10-14 days after completion of treatment with active drug. Analysis was by per protocol. This trial is registered with EudraCT, number 2005-004992-39, and ClinicalTrials.gov, number ISRCTN73338924. FINDINGS 126 of 248 patients were randomly assigned to 7 days and 122 to 14 days of ciprofloxacin. 73 and 83 patients, respectively, were analysed. Short-term clinical cure occurred in 71 (97%) patients treated with ciprofloxacin for 7 days and 80 (96%) treated for 14 days (difference -0·9%; 90% CI -6·5 to 4·8; p=0·004; non-inferiority test). Cumulative efficacy at long-term follow-up was 93% in each group (68 of 73 vs 78 of 84; -0·3%; -7·4 to 7·2; p=0·015). Both regimens were well tolerated. Two patients discontinued ciprofloxacin because of myalgia with 7 days of treatment and itching exanthema with 14 days. Four (5%) of 86 patients assigned to 7 days of treatment who complied with study criteria and six (6%) of 93 assigned to 14 days reported an adverse event after the first week of treatment that was possibly or probably related to the study drug. In those assigned to 7 days, no patient had mucosal candida infection after the first week versus five treated for 14 days (p=0·036). INTERPRETATION Our results show that acute pyelonephritis in women, including older women and those with a more severe infection, can be treated successfully and safely with oral ciprofloxacin for 7 days. Short courses of antibiotics should be favoured in an era of increasing resistance. FUNDING Swedish Strategic Programme against Antibiotic Resistance (Strama).

Phylogenetic and Pathotypic Comparison of Concurrent Urine and Rectal Escherichia coli Isolates from Men with Febrile Urinary Tract Infection

ABSTRACT Among men with febrile urinary tract infection (FUTI), whether the hosts fecal flora is the source for the urine strain (“fecal-urethral” hypothesis), and whether pathogenesis is driven by prevalence versus special pathogenicity, are unknown. Accordingly, pretherapy urine isolates from 65 men with FUTI were compared with concurrent rectal isolates from the same hosts according to serotype, genomic profile, phylogenetic group, and virulence genotype. The hosts multiple rectal colonies included only the urine clone in 25% of subjects, the urine clone plus additional clones in 22%, and only nonurine clones in 54%. Compared with the 67 unique rectal clones, the 65 urine isolates were significantly enriched for phylogenetic group B2, virulence-associated serotypes, and specific virulence genes and contained more virulence genes (median, 10 versus 6: P < 0.001). In multivariable models, phylogenetic group B2, hlyD (hemolysin), cnf1 (cytotoxic necrotizing factor), iroN (siderophore receptor), ompT (outer membrane protease), and malX (pathogenicity island marker) most strongly predicted urine source. These findings challenge the fecal-urethral and prevalence hypotheses for FUTI pathogenesis and instead strongly support the possibility of alternate infection routes in some men and the special pathogenicity hypothesis. They also identify specific bacterial traits as potential targets for anti-FUTI interventions.

Symptomatic urinary tract infection in women in primary health care: Bacteriological, clinical and diagnostic aspects in relation to host response to infection

OBJECTIVE To evaluate rapid diagnostic tests for bacteriuria in women with symptoms of urinary tract infection (UTI), and to analyse bacteriological and clinical findings in relation to host response to infection. DESIGN Prospective study of symptomatic UTI in women. SETTING Primary health care centres. PATIENTS 819 women with signs and symptoms suggestive of UTI. MAIN OUTCOME MEASURES History of UTI and clinical findings were recorded. After randomization but before antibiotic treatment, urine specimens were analysed for pyuria by sediment microscopy and for nitrite using a test strip, and cultures were performed. The systemic inflammatory response was assessed by C-reactive protein (CRP), erythrocyte sedimentation rate, and total white blood cell count. RESULTS The combined use of tests for pyuria and nitrite resulted in a high sensitivity (0.93) and efficacy (0.85) when the prevalence of bacteriuria was 0.89. Escherichia coli and Staphylococcus saprophyticus accounted for 93% of the urinary isolates. Significantly more patients infected with S. saprophyticus than E. coli complained of dysuria (p < 0.05), frequency (p < 0.05) or flank pain (p < 0.01). CRP agreed best with the clinical diagnosis of acute pyelonephritis. CONCLUSIONS In women with a high probability of bacteriuria, i.e. those with symptoms of lower UTI, examination for pyuria and urinary nitrite offers high diagnostic efficacy. If either or both tests are positive urine cultures can be omitted.

Selective urological evaluation in men with febrile urinary tract infection.

Objective To investigate the prevalence and clinical importance of urological abnormalities in men with community‐acquired febrile urinary tract infection (UTI).

Antibiotic prophylaxis in surgery: Summary of a Swedish-Norwegian Consensus Conference

This consensus document sets out proposals for antibiotic prophylaxis in abdominal, urological, gynaecological, orthopaedic, vascular and thoracic surgery. As far as possible the recommendations are based on prospective controlled trials. However, for some procedures, e.g. lung surgery and implantation of pacemakers, documentation is lacking but antibiotic prophylaxis is given traditionally. The choice of antibiotics is generally conservative, emphasizing that antibiotics used for therapy should be avoided in prophylactic regimens. Most recommendations are for the use of a first- or second-generation cephalosporin or an isoxazolyl penicillin, when necessary, combined with a nitroimidazole derivative (metronidazole or tinidazole). Suggestions are given for more frequent use of orally administered antibiotics, such as co-trimoxazole, doxycycline, metronidazole or tinidazole. Emphasis is put on short-term prophylaxis. In most cases surgical antibiotic prophylaxis should be given as a single dose and in no case should the prophylaxis time exceed 24 h.

Host-Pathogen Relationships among Escherichia coli Isolates Recovered from Men with Febrile Urinary Tract Infection

BACKGROUND Host-pathogen relationships in men with febrile urinary tract infection (FUTI) are poorly understood. METHODS Phylogenetic background, extended virulence genotypes, and serotypes were determined for 70 Escherichia coli isolates recovered from urine samples obtained from men with FUTI for comparison with available data for 70 E. coli rectal isolates recovered from uninfected men. Bacterial traits were assessed in relation to underlying host characteristics (age, compromise status, and history of urinary tract infection) and acute manifestations (bacteremia, flank pain, and serum prostate-specific antigen [PSA] level). RESULTS Compared with rectal isolates, FUTI isolates exhibited a significantly higher prevalence of virulence-associated phylogenetic groups, serotypes, and extraintestinal virulence genes. The latter included traditional prostatitis-associated traits (e.g., hemolysin and cytotoxic necrotizing factor), as well as unconventional traits, such as outer membrane protease T. These bacterial traits occurred largely independent of host age, urological compromise status, urinary tract infection history, and acute manifestations. However, certain traits were less prevalent in association with use of urinary tract instrumentation and significantly predicted elevated PSA levels. CONCLUSIONS Considerable virulence capability may be required for an E. coli strain to cause FUTI in men, regardless of whether most compromising conditions are present. Bacterial traits that promote prostatic invasion may be relevant for the pathogenesis of FUTI, even among men without classic manifestations of acute prostatitis.

Evolution of free, complexed, and total serum prostate-specific antigen and their ratios during 1 year of follow-up of men with febrile urinary tract infection

OBJECTIVES To determine the serum values of free, complexed, and total prostate-specific antigen (PSA) and their ratios in men with febrile urinary tract infection (UTI) during 1 year of follow-up. METHODS A total of 54 men were prospectively enrolled in the study, and serum samples were obtained at the acute stage of the UTI and after 1, 3, 6, and 12 months. RESULTS Most men had a rise (median 3.1, 7.2, and 14.1 ng/mL, respectively) in free PSA (fPSA), complexed PSA (cPSA), and total PSA (tPSA) during the acute phase of the UTI. After 1 month, fPSA rapidly decreased to levels that were maintained during the rest of the follow-up period, and cPSA and tPSA declined more slowly. At 1, 3, and 6 months after the infection the fPSA/tPSA and fPSA/cPSA ratios were abnormal in one half to two thirds of the men (median ratio 11%, 15%, and 16% and 17%, 24%, and 24%, respectively), comparable to findings in patients with prostate cancer. CONCLUSIONS These results confirmed that the prostate is involved in men with febrile UTI. The low fPSA/tPSA and fPSA/cPSA ratios in combination with sustained elevations of cPSA and tPSA for up to 6 months after UTI could be falsely interpreted as a sign of prostate cancer. The prolonged elevation of cPSA indicates a long-lasting inflammation of the nonadenomatous parts of the prostate.

A longitudinal cohort study of elderly women with urinary tract infections.

AIMS the prevalence of urinary tract infections (UTI), urinary incontinence (UI), estrogen-use and overall mortality in a cohort of elderly women who had been treated for UTI in 1985-86 was re-assessed 10 years later. MATERIAL AND METHODS a random sample of 6000 women from the birth cohorts 1900, 1905, 1910, 1915 and 1920 were invited in 1986 to complete a questionnaire about UTI, UI and estrogen use (response rate 70%; n = 4206). Treatment with antibiotics for UTI during 1985-86 was reported by 688 (17%) women. In 1995 a similar questionnaire was sent to the women from this group who were still alive (n = 434). Mortality in the women with a history of UTI was compared with an aged-matched control group of women who did not have UTI during 1985-86. RESULTS the questionnaire was completed and returned by 361 (83%) women. Treatment for at least one UTI during the last 9 years was reported by 219 (61%) women. The number of episodes varied: 35% had one to two UTI, 28% had three to four UTI, 27% five to ten UTI and 10% had had more than 10 UTI. In 1986, the prevalence of UI was higher in women with a history of UTI than in the total population sample (30 vs. 17%; P < 0.001). The prevalence of UI had increased from 30% in 1986 to 33% in 1995 (P < 0.05). Mortality in the women with a history of UTI was higher than in the aged-matched control group (37 vs. 28%; P < 0.001). A total of 162 (45%) women had received estrogen therapy at some time after the age of 60 years and 140 (39%) reported that they were currently taking low potency estrogens. CONCLUSION elderly women with a history of UTI had a continued high occurrence of UTI and UI, and overall mortality was higher in these women than in an age-matched control group of women from the total population.

Sexual Acquisition of Acute Pyelonephritis in a Man

A 51-year-old man presented with acute cystitis at a time when his wife was admitted with symptoms of acute pyelonephritis. Before the man developed his symptoms his wife had complained of urinary frequency and dysuria for a 2-week period. Two weeks after a 10-day course with trimethoprim he experienced a relapse manifesting as acute febrile pyelonephritis. The strains of Escherichia coli isolated from the urine of both patients belonged to the same serotype O51, O117:K1, were non-haemolytic, produced aerobactin, expressed P-fimbriae, and showed identical antibiotic susceptibility pattern. The findings strongly suggest that the E. coli strain might have been sexually transmitted from the wife to her husband.