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ObjectiveEarlier studies on antibiotics exposure and development of IBD (Crohn’s disease (CD) and ulcerative colitis (UC)) may have been biased by familial factors and gastroenteritis. We aimed to estimate the association between antibiotics during pregnancy or infantile age and very early onset (VEO) IBD.DesignIn this cohort study of 827 239 children born in Sweden between 2006 and 2013, we examined the link between exposure to systemic antibiotics and VEO-IBD (diagnosis <6 years of age), using Cox proportional hazard regression models. Information on antibiotics and IBD was retrieved from the nationwide population-based Swedish Prescribed Drug Register and the National Patient Register. We specifically examined potential confounding from parental IBD and gastroenteritis.ResultsChildren exposed to antibiotics during pregnancy were at increased risk of IBD compared with general population controls (adjusted HR (aHR) 1.93; 95% CI 1.06 to 3.50). Corresponding aHRs were 2.48 (95% CI 1.01 to 6.08) for CD and 1.25 (95% CI 0.47 to 3.26) for UC, respectively. For antibiotics in infantile age, the aHR for IBD was 1.11 (95% CI 0.57 to 2.15); for CD 0.72 (95% CI 0.27 to 1.92) and 1.23 (95% CI 0.45 to 3.39) for UC. Excluding children with gastroenteritis 12 months prior to the first IBD diagnosis retained similar aHR for antibiotics during pregnancy and CD, while the association no longer remained significant for IBD.ConclusionWe found that exposure to antibiotics during pregnancy, but not in infantile age, is associated with an increased risk of VEO-IBD regardless of gastroenteritis. The risk increase for exposure in pregnancy may be due to changes in the microbiota.

Nitrofurantoin, trimethoprim–sulfamethoxazole, fosfomycin, and pivmecillinam are considered first-line agents for cystitis. Fluoroquinolones should not be routine first-line choices for cystitis, although they are first-line empirical therapy for pyelonephritis. Foreword This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author's clinical recommendations. Stage A 30-year-old woman calls you to report a 2-day history of worsening dysuria and urinary urgency and frequency. She reports having no fever, chills, back pain, or vaginal irritation or discharge. One month ago, you treated her with a 3-day course of trimethoprim–sulfamethoxazole for presumptive cystitis, and her symptoms resolved. She is otherwise healthy, but this is her third episode in the past year. How should her case be managed? The Clinical Problem Incidence Urinary tract infection is the most common bacterial infection encountered in the ambulatory care setting in the United States, accounting for 8.6 million visits (84% . . .

Antibiotic resistance is one of the most urgent threats to public health. The development of antibiotic resistance can be reduced by the use of narrow-spectrum antibiotics that target specific bacteria, meaning that fewer non-harmful bacteria are killed and other harmful bacteria are not exposed to selection pressure. However, many narrow-spectrum antibiotics were introduced decades ago and therefore lack regulatory documentation in line with current standards. An additional problem for a reliable supply is that of market fragmentation, where countries with similar resistance patterns and prescribing cultures (e.g. Norway and Sweden) prioritize different formulations and strengths. For example, over half of Sweden's highest priority paediatric antibiotics are not marketed in Denmark or Norway in the same formulations or dosages. Such market fragmentation, which can result in the annual demand of a country being smaller than batch production sizes, means that specific strengths and formulations may no longer be economical to supply. Further, once an antibiotic has been withdrawn from the market, it is difficult to attract a new supplier because of the cost of the clinical trials required to update approval of the drug. However, as resistance to antibiotics increases among populations, clinicians need access to the maximum possible range of antibiotics. Regional collaboration, that is, the harmonization of essential medicines lists (including strengths and formulations for older antibiotics) between countries, is a recommended first step towards reliable access to the necessary range of antibiotics.

Although uncomplicated urinary tract infections (UTIs) are often self-limiting, most patients will be prescribed antibiotic treatment. We assessed whether treatment with ibuprofen was non-inferior to pivmecillinam in achieving symptomatic resolution by day 4, with a non-inferiority margin of 10%. This was a randomized, controlled, double-blind non-inferiority trial. We recruited patients from 16 sites in a general practice setting in Norway, Sweden, and Denmark. Non-pregnant women aged 18-60 years presenting with symptoms of uncomplicated UTI were screened for eligibility from 11 April 2013 to 22 April 2016. Patients with informed consent were randomized (1:1 ratio) to treatment with either 600 mg ibuprofen or 200 mg pivmecillinam 3 times a day for 3 days. The patient, treating physician, and study personnel were blinded to treatment allocation. The primary outcome was the proportion of patients who felt cured by day 4, as assessed from a patient diary. Secondary outcomes included the proportion of patients in need of secondary treatment with antibiotics and cases of pyelonephritis. A total of 383 women were randomly assigned to treatment with either ibuprofen (n = 194, 181 analyzed) or pivmecillinam (n = 189, 178 analyzed). By day 4, 38.7% of the patients in the ibuprofen group felt cured versus 73.6% in the pivmecillinam group. The adjusted risk difference with 90% confidence interval was 35% (27% to 43%) in favor of pivmecillinam, which crossed the prespecified non-inferiority margin. Secondary endpoints were generally in favor of pivmecillinam. After 4 weeks' follow-up, 53% of patients in the ibuprofen group recovered without antibiotic treatment. Seven cases of pyelonephritis occurred, all in the ibuprofen group, giving a number needed to harm of 26 (95% CI 13 to 103). Five of these patients were hospitalized and classified as having serious adverse events; 2 recovered as outpatients. A limitation of the study was the extensive list of exclusion criteria, eliminating almost half of the patients screened. We did not register symptoms in the screening process; hence, we do not know the symptom burden for those who declined to participate. This might make our results less generalizable. Ibuprofen was inferior to pivmecillinam for treating uncomplicated UTIs. More than half of the women in the ibuprofen group recovered without antibiotics. However, pyelonephritis occurred in 7 out of 181 women using ibuprofen. Until we can identify those women who will develop complications, we cannot recommend ibuprofen alone as initial treatment to women with uncomplicated UTIs. ClinicalTrials.gov NCT01849926 EU Clinical Trials Register (EU-CTR), EudraCT Number 2012-002776-14.

Shigellosis is a severe gastrointestinal disease that annually affects approximately 270 million individuals globally. It has particularly high morbidity and mortality in low-income regions; however, it is not confined to these regions and occurs in high-income nations when conditions allow. The ill effects of shigellosis are at their highest in children ages 2 to 5, with survivors often exhibiting impaired growth due to infection-induced malnutrition. The escalating threat of antibiotic resistance further amplifies shigellosis as a serious public health concern. This review explores Shigella pathology, with a primary focus on the status of Shigella vaccine candidates. These candidates include killed whole-cells, live attenuated organisms, LPS-based, and subunit vaccines. The strengths and weaknesses of each vaccination strategy are considered. The discussion includes potential Shigella immunogens, such as LPS, conserved T3SS proteins, outer membrane proteins, diverse animal models used in Shigella vaccine research, and innovative vaccine development approaches. Additionally, this review addresses ongoing challenges that necessitate action toward advancing effective Shigella prevention and control measures.

This study aimed to retrospectively assess the clinical outcome with nitrofurantoin and pivmecillinam for lower urinary tract infections (UTI) in men. Patients treated with trimethoprim were also included for comparison. All prescriptions of the study antibiotics to adult men in Uppsala County, Sweden, during 2012 were extracted. Data on patient characteristics, therapy, clinical outcome and microbiological results were obtained from the electronic medical records. The relative impact of antibiotic therapy, patient factors and pathogens on clinical outcome was assessed with univariate logistic regression using a 95% confidence interval (CI). 832 prescriptions were identified, and 171 patients treated with nitrofurantoin (n = 69), pivmecillinam (n = 57) and trimethoprim (n = 45) met the inclusion criteria. Treatment failure occurred in one patient treated with nitrofurantoin and in four patients treated with pivmecillinam. New prescriptions of UTI antibiotics and relapse within 3 months after completion of therapy were more frequent with nitrofurantoin (34% and 15%) and pivmecillinam (30% and 17%) than trimethoprim (22 and 7%). However, these differences were not statistically significant and substantial heterogeneity was noted between the treatment groups. Urinary tract catheterization was associated with a higher risk for new antibiotic prescriptions (OR 2.34, 95% CI 1.14-4.80; P = 0.022) and prostate cancer was associated with a higher incidence of relapse (OR 3.01, 95% CI 1.09-8.29; P = 0.042). The clinical outcome with nitrofurantoin and pivmecillinam was acceptable in comparison with the results of previous studies. These antibiotics are suitable for empirical treatment of lower UTI in men considering their high activity against Escherichia coli and limited impact on the intestinal microbiota.

To estimate the incidence of pyelonephritis in primary care in Spain from 2009 to 2018, assess the associated antibiotic prescriptions, and analyse trends by sex and age. This is a retrospective observational population-based national study using the Database for Pharmacoepidemiological Research in the Public Domain (BIFAP), which contains primary care electronic medical records, and is representative of the Spanish population. Patients with a diagnosis of pyelonephritis were included. Sociodemographic and clinical data were collected. Crude and adjusted incidence rates were calculated per 10,000 person-years by sex and age, and annual and global percentages of antibiotic use were calculated by sex, age, and antibiotic group. Trend analysis was performed using a joinpoint regression model. 24,888 cases of pyelonephritis were recorded with an incidence of 4.2/10,000 person-years (6.6 women vs 1.5 men). An annual decreasing trend was observed in women (AAPC average annual percentage change) -2.7 (95% CI -4.4;-0.9), men -3.0 (95% CI -4.5;-1.5), patients aged 18-64 years -2.9 (95% CI -4.7;-0.9) and ≥ 65 years -4.2 (95% CI -5.8;-2.4). The most frequently used groups of antibiotics were cephalosporins (38.7%), quinolones (30%), combined penicillins (22.2%) and fosfomycin (6.8%). Cephalosporin prescription predominated in women (39.8%), and quinolone prescription in men (40.3%). The most prescribed cephalosporins were third and second generation (21% and 17.7% respectively). A downward annual trend was observed in the global use of antibiotics AAPC -0.8 (95% CI -1.4; -0.2), with an increasing AAPC 1.7 (95% CI -0.6; 3.4) in ≥65 years. Among the groups of antibiotics, the prescription of quinolones AAPC -6.9 (95% CI -31.7;17.3) and penicillins AAPC -8.7 (95% CI -11.2;-6.8) decreased and cephalosporins increased AAPC 19.0 (95% CI 12.2;26). Women had a fourfold higher incidence of acute pyelonephritis than men, with a decreasing trend over the study period. Cephalosporins were the most commonly prescribed antibiotics in women, while quinolones were more common in men. An increasing trend in cephalosporin use and a decreasing in quinolone use were observed.