High Cytokine Levels in Tonsillitis Secretions Regardless of Presence of Beta-Hemolytic Streptococci.

Acute pharyngotonsillitis denotes tonsillar inflammation caused by bacteria or viruses. Here, we investigated if beta-hemolytic streptococci (ß-HS) tonsillitis would differ in inflammatory mediator response from tonsillitis of other causes. Tonsillar secretions were obtained from 36 acute pharyngotonsillitis patients and 16 controls. Bacteria were cultured quantitatively and 18 different viruses were quantified by real-time polymerase chain reaction. Cytokine and prostaglandin E2 (PGE2) levels were determined by enzyme-linked immunosorbent assays. Almost half of the patients' tonsillar secretions yielded high counts of ß-HS, and most samples contained viruses, irrespective of whether ß-HS were present or not. The Epstein-Barr virus (EBV) was the most common virus (patients 62% and controls 13%). Compared to controls, patients' secretions had higher levels of interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor (TNF), and PGE2, while few samples contained IL-12, IL-10, or interferon-gamma (IFN-γ). The presence of ß-HS in tonsillitis secretions could not be distinguished by any of the measured mediators, while the presence of EBV DNA tended to be associated with enhanced levels of IL-1ß and IL-8. The results suggest a common inflammatory response in acute pharyngotonsillitis, regardless of causative agent. The suggested correlation between intense inflammation and the presence of EBV DNA in tonsillitis secretions may be due to reactivation of the virus and/or the EBV-containing B cells.

Mecillinam resistance and outcome of pivmecillinam treatment in uncomplicated lower urinary tract infection in women.

Pivmecillinam (PIV) is a first-line antimicrobial for treatment of lower urinary tract infection in women (LUTIW). Mecillinam, the active substance of PIV, is bactericidal mainly against gram-negative uropathogens, whereas gram-positive species are considered intrinsically resistant. However, successful treatment of LUTIW caused by Staphylococcus saprophyticus has been reported, but more rarely for other gram-positive species. The aim of this study was to compare clinical and bacteriological outcome of PIV vs placebo treatment among uropathogens with special focus on mecillinam-resistant isolates. We analysed data from a prospective, multicentre, placebo-controlled, primary health care, therapy study performed in Sweden in 1995­1998 that included 1143 women with symptoms suggestive of LUTIW. Urine cultures were collected and symptoms registered at inclusion and at follow-up visits. Overall, the efficacy of PIV was superior to that of placebo. Clinical and bacteriological outcomes of PIV treatment were similar for S. saprophyticus, Escherichia coli as for most other uropathogens irrespective of their susceptibility to mecillinam. However, the occurrence of enterococci increased nearly fivefold shortly post PIV treatment, although with mild symptoms and a high spontaneous eradication. As susceptibility to mecillinam in vitro did not predict bacteriological and clinical outcome of PIV treatment, we suggest that the present breakpoints for mecillinam should be revised.

Characteristics of Escherichia coli causing persistence or relapse of urinary tract infections: phylogenetic groups, virulence factors and biofilm formation.

Recurrent urinary tract infections (RUTIs) pose a major problem but little is known about characteristics of Escherichia coli associated with RUTI. This study includes E. coli from 155 women with community-acquired lower urinary tract infections (UTIs) randomized to one of three dosing regiments of pivmecillinam and aimed to identify associations between the presence of 29 virulence factor genes (VFGs), phylogenetic groups and biofilm formation and the course of infection during follow-up visits at 8-10 and 35-49 days post-inclusion, respectively. E. coli causing persistence or relapse were more often of phylogenetic group B2 and had a significantly higher aggregate VFG score than E. coli that were not detectable at follow-up. Specifically, these E. coli causing persistence or relapse were characterized by a higher prevalence of hemolysis and 12 VFGs (sfa/focDE, papAH, agn43, chuA, fyuA, iroN, kpsM II, kpsM II K2, cnf1, hlyD, malX and usp). KpsM II K2 and agn43a(CFT073) were independently associated with persistence or relapse. No specific combination of presence/absence of VFGs could serve as a marker to predict RUTI. Stratifying for VFGs, seven days of pivmecillinam treatment reduced the prevalence of persistence or relapse of UTI compared with three days. In vitro biofilm formation was not higher among E. coli causing persistence or relapse. The presence of agn43a(CFT073) or agn43b(CFT073) was associated with biofilm forming capacity. In conclusion, our results show potential targets for prevention and treatment of persistence/relapse of UTI and potential markers for selecting treatment lengths and warrant studies of these and new VFGs.

Clinical and bacteriological outcome of different doses and duration of pivmecillinam compared with placebo therapy of uncomplicated lower urinary tract infection in women: the LUTIW project.

OBJECTIVE: To analyse associations between symptoms and bacteriuria in uncomplicated lower urinary tract infection in women (LUTIW) and to evaluate outcome of therapy with three different regimens of pivmecillinam or placebo. DESIGN: Prospective, multicentre, randomized, double-blind, and placebo-controlled therapy study. Symptoms registered at inclusion, during therapy and at follow-up visits after 8-10 and 35-49 days. Significant bacteriuria defined according to current European guidelines. SETTING: A total of 18 primary healthcare centres in northern Sweden. Subjects. Women aged 18 years and above with symptoms of urgency, dysuria, supra pubic or loin pain. Main outcome measures. Symptoms and bacteriuria at inclusion and course of symptoms, bacteriuria, and their combinations during and post-therapy. RESULTS: At inclusion, no associations or significant differences were found between symptom scores and bacteriuria, bacterial counts, or species. The 884 patients (77%) with significant bacteriuria were followed up. All pivmecillinam therapies were superior to placebo (p < 0.001). From day six until first follow-up, the mean values of all symptoms were higher and the bacteriological cure was lower at first follow-up in the three days (84%) compared with the seven days regimens (93-94%, p < 0.001). At final follow-up clinical cure was similar in all pivmecillinam regimens (65-72%) as was bacteriological cure (83-89%). Pivmecillinam had few low to mild adverse reactions, comparable to placebo. CONCLUSIONS: Symptoms are not conclusive for diagnosis of LUTIW. Pivmecillinam therapies are superior to placebo and seven days regimens are more efficient than three days. Pivmecillinam 200 mg x 2 x 7 days is recommended as a first-line therapy for LUTIW.

The natural course of uncomplicated lower urinary tract infection in women illustrated by a randomized placebo controlled study.

This prospective, multicentre, randomized, double-blind and placebo controlled study was performed to describe the natural course of uncomplicated lower urinary tract infection (UTI). A total of 1143 women 18 y and above, consulting at 18 primary health care centres in northern Sweden for symptoms suggestive of UTI were included. The symptoms urgency, dysuria, suprapubic pain and loin pain were registered, and urine cultures performed at inclusion and follow-up visits 8-10 d and 5-7 weeks later. Associations between all symptoms and bacteriuria or bacterial counts were unpredictable. Eradication of symptoms and bacteriuria and combinations of them were studied in 288 patients placebo treated for 7 d, of whom 39% dropped out after the first follow-up visit. The spontaneous cure rate of symptoms was 28% after the first week, and 37% had neither symptoms nor bacteriuria after 5-7 weeks. Considering the high dropout rate after the first follow-up visit, the spontaneous cure rate of symptoms and bacteriuria was calculated to 24% at the end of study. We conclude that patient near-laboratory tests are required to establish the diagnosis of lower UTI, and the guidelines for diagnosis of UTI need to be revised.

Is hydrogen peroxide responsible for the inhibitory activity of alpha-haemolytic streptococci sampled from the nasopharynx?

OBJECTIVE: The inhibitory effect of alpha-haemolytic Streptococci (AHS) in vitro on the three commonest otitis media pathogens, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, was previously investigated. The aim of this study was to determine the mechanism of this inhibitory activity. MATERIAL AND METHODS/RESULTS: When fractions of AHS filtrate were assayed to determine their inhibitory activity after size-exclusion chromatography, the inhibitory activity was found in the fractions with a low molecular weight. The inhibitory effect was completely reversed when catalase was added to the cell-free filtrate of AHS. A quantitative method also revealed high production (approximately 3 mmol/l) of hydrogen peroxide in the AHS filtrate with the best inhibitory activity. Electron microscopy of bacteria exposed to AHS filtrate with an inhibitory effect showed changes similar to bacteria exposed to hydrogen peroxide. CONCLUSIONS: We conclude that the inhibitory effect of AHS is most likely due to the production of hydrogen peroxide. The significance of hydrogen peroxide production of AHS is discussed in relation to the non-specific and specific mucosal defence systems.

Bacterial interference between pathogens in otitis media and alpha-haemolytic Streptococci analysed in an in vitro model.

Bacterial interference studied by means of agar methods has shown a decreased number of inhibitory alpha-haemolytic Streptococci among otitis-prone children. Additional information was gained regarding the interplay between alpha-haemolytic Streptococci (AHS) and otitis media (OM) pathogens by comparing the bacterial interference in broth with the interference activity studied using agar overlay methods. We found, that non-typeable Haemophilus influenzae (NTHI) and Moraxella catarrhalis are readily inhibited by AHS in broth. Streptococcus pneumoniae was more bacteriostatically inhibited. If two OM pathogens were inoculated simultaneously, an isolate of AHS with poor inhibitory activity was not able to inhibit the growth, in contrast to an isolate of AHS with good inhibitory activity. The initial amount of AHS inoculated with M. catarrhalis seemed to play a decisive role with respect to the inhibitory activity. M. catarrhalis developed reduced susceptibility against AHS both in vivo and in vitro. In vivo studies showed that children with secretory otitis media had fewer isolates of AHS in their nasopharynx with the ability to inhibit all the test pathogens than healthy children (p < 0.001). Although the factor(s) responsible for the inhibitory activity have thus far not been defined, we could exclude low pH and nutrition depletion as the inhibitory mechanism of AHS with good inhibitory activity.

A nasal spray with alpha-haemolytic streptococci as long term prophylaxis against recurrent otitis media.

Previous studies have shown that children with recurrent acute otitis media (rAOM) have significantly lower quantities of alpha-haemolytic streptococci (AHS) in the nasopharynx than healthy children. Furthermore children with otitis media have AHS with lower inhibitory activity in vitro on Streptococcus pneumoniae and non-typable Haemophilus influenzae compared with healthy children. A randomised, placebo controlled and double blind clinical study among children with rAOM was designed to determine whether or not a nasal spray, containing AHS with very good inhibitory activity on the three most common OM pathogens, could be an alternative to tympanostomy tube insertion. Forty three children under 4 years of age were included in the study. The children sprayed once daily for 4 months and were monitored for 6 months. Sixteen children in the active group and 20 children in the placebo group were evaluated. The result showed no significant differences regarding the number of episodes of AOM, with seven recurrences in the active group and eight in the placebo group. No significant changes of the nasopharyngeal flora could be detected during the study period regarding the OM pathogens. Nasal spray according to the performed schedule is not yet an alternative to tympanostomy tubes in children with rAOM. The possibility of increasing the efficacy of this ecological treatment, by using pre-treatment antibiotics, more adhesive bacteria and alternative treatment schedules is discussed.

Stomatococcus mucilaginosus septicemia in leukemic patients.

OBJECTIVE: To report an unexpectedly high number of cases of septicemia with Stomatococcus mucilaginosus, and try to identify predisposing factors. METHODS: All blood cultures obtained during 1991--93 from patients treated at the hematologic ward were bacteriologically identified. The medical records of patients with S. mucilaginosus-positive blood cultures were retrospectively reviewed and evaluated. The antibiotic susceptibility pattern and restriction fragment length polymorphism (RFLP) of S. mucilaginosus were tested. RESULTS: S. mucilaginosus blood isolates from patients with hematologic malignancies were found to be as common as isolates of Staphylococcus aureus. Eleven patients with myelogenous leukemia and isolation of S. mucilaginosus from the blood are reported on. One patient had concomitant meningitis. All patients were neutropenic and most had oral mucositis and had been given ciprofloxacin prophylaxis. S. mucilaginosus isolates from these patients were resistant to ciprofloxacin in contrast to isolates from patients who had received other prophylactic regimens and seven isolates found in healthy individuals not recently treated with antibiotics. The resistant S. mucilaginosus were found to be of diverse genetic origin as determined by RFLP. CONCLUSIONS: The appearance of resistant strains during ciprofloxacin prophylaxis may be a predisposing factor for S. mucilaginosus septicemia. There was no evidence of a nosocomial spread of S. mucilaginosus strains.