Impact of multiplex respiratory virus testing on antimicrobial consumption in adults in acute care: a randomized clinical trial.

OBJECTIVES: Inappropriate use of antibiotics is associated with development of antimicrobial resistance. In respiratory infections it is often difficult to differentiate between viral and bacterial infections, and empirical treatment is common. Enhanced viral testing is expected to clarify clinical decision-making and reduce the prescription of antibacterial agents, but the impact of such information on patient care is unclear. METHODS: We conducted a (1:1) randomized controlled clinical trial involving 998 adults with respiratory symptoms, fever, chest pain or poor general condition in the emergency unit of a tertiary hospital. Multiplex PCR results for 496 patients were available in 24 hours (intervention group) and those for the remaining 502 patients were available in 7 days (control group). Our primary outcome measures were the duration of hospitalization and the consumption of antibiotics within 30 days of enrolment. RESULTS: In all, 841 of 998 (84%) patients had respiratory symptoms at study entry. A respiratory virus was detected in 175 (17.5%). The mean duration of hospitalization was 4.2 days (SD 5.4) in the intervention group and 4.1 days (SD 4.9) in the control group (difference 0.1, 95% CI -0.5 to 0.6, p 0.810). The mean days on antibiotics were 11.3 days (SD 12.6) in the intervention group and 10.4 days (SD 11.4) in the control group (difference 0.9, 95% CI -0.6 to 2.4, p 0.235). CONCLUSIONS: Multiplex PCR testing for respiratory viruses with results available within 24 hours did not reduce the consumption of bacterial antibiotics or the length of hospital stay in adults presenting with respiratory symptoms, fever, chest pain or reduced general condition in acute care.

Tonsillar microbiota in children with PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and adenitis) syndrome.

Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) is a childhood febrile syndrome of unknown origin that is often cured with tonsillectomy. We aimed to compare the bacterial microbiota of the tonsils removed from PFAPA patients with those of controls. We used next-generation sequencing technology to investigate the bacterial microbiota of the tonsils of 30 PFAPA patients and 24 controls. We found significant differences in the presence and relative abundance of many bacteria between PFAPA cases and controls. For example, cyanobacteria, potential producers of microcystins and other toxins, were more common in the case samples (14/30, 47 %) than in the controls (4/24, 17 %, p = 0.02), and the mean relative abundance of cyanobacteria was higher in the case samples (0.2 %) than in the controls (0.01 %, p = 0.01). Streptococci were present in all samples in both groups, but their mean relative abundance was lower in the case samples (3.7 %) than in the controls (9.6 %, p = 0.01). Typical nasopharyngeal microbes such as fusobacteria, Prevotella, Tannerella, Porphyromonas, and Parvimonas dominated the microbiota of the tonsils in both groups. The microbiota of the tonsils removed from PFAPA patients differed significantly from those of the controls. Tonsillar microbiota may play a role in triggering the inflammatory processes that lead to symptoms of PFAPA.

Escherichia coli biofilm formation and recurrences of urinary tract infections in children.

It has been suggested that biofilm formation by uropathogenic Escherichia coli (UPEC) isolates is associated with recurrence and persistence of urinary tract infection (UTI). We compared the in vitro biofilm formation of UPEC isolates from children with acute or recurrent UTI. Employing 206 consecutive clinical UPEC isolates from children with proven UTI, i.e., pyelonephritis (n = 78), recurrent pyelonephritis (n = 10), cystitis (n = 84) or recurrent cystitis (n = 34), we applied 1 % crystal violet staining to polystyrene microtitre plates at 72 h and measured the optical density (OD) values. The method had been validated to measure biofilm formation against confocal laser scanning microscopy and scanning electron microscopy. The OD values were lower in the recurrent cystitis group than in the other groups (mean OD 0.36, SD 0.21 vs mean 0.47, SD 0.36, P = 0.04) and higher in the recurrent pyelonephritis group than in the other groups (mean OD 0.69, SD 0.33 vs mean OD 0.44, SD 0.34, P = 0.006) indicating biofilm formation of strains causing recurrent pyelonephritis. It appears that the properties of UPEC isolates required for effective biofilm growth on an abiotic surface are important for recurrent pyelonephritis, but not for recurrent cystitis. It would be valuable in the future to analyze whether the biofilm properties of E. coli observed in vitro predict a slower clinical response to antimicrobial treatment and increased renal scar formation after UTI.

Biofilm formation and virulence of uropathogenic Escherichia coli in urine after consumption of cranberry-lingonberry juice.

Cranberry-lingonberry juice (CLJ) was effective in preventing urinary tract infections (UTIs) in our earlier randomized clinical trial. We aimed to test whether consumption of CLJ at a similar dose to earlier reduces the biofilm formation and virulence of uropathogenic Escherichia coli in urine. Twenty healthy women drank 100 ml of CLJ daily for two weeks. Urine samples were obtained 2-4 hours after the last dose. Control samples were taken after a one-week period without berry consumption. Biofilm formation of 20 E. coli strains was measured at 72 hours by the polystyrene microtitre plate method. Quantitative real-time PCR analyses were performed for selected genes. Four of the 20 clinical strains produced more biofilm in urine after CLJ consumption (P < 0.05) and one produced less. Expression levels of the pga, cpxA, fimA and papF genes did not differ between bacteria grown in control urine and urine obtained after CLJ consumption, except for pga gene expression, which was reduced in one strain after CLJ (P = 0.04). It appears that the effect of CLJ in preventing UTIs is not explained by mechanisms that reduce biofilm formation or the expression of selected virulence genes of Escherichia coli in urine.

Post-discharge follow-up of hospital-associated infections in paediatric patients with conventional questionnaires and electronic surveillance.

BACKGROUND: Viral infections are common causes of hospital-associated infections (HAIs) in paediatric patients, with most of these infections only becoming evident after discharge. AIM: To analyse the benefits and costs of conventional and electronic surveillance methods for conducting HAI follow-ups. METHODS: A comparison was made between response rate, time required per patient and costs to the healthcare system of conventional and electronic surveillance methods (sms, e-mail, telephone call). FINDINGS: Altogether 1927 patients participated in the conventional followed up in 2001-2003, of whom 1175 (61%) returned the questionnaire; during the electronic surveillance period in 2005-2007, 2309 patients were followed-up in hospital, and 1940 of them (84%) returned the post-discharge information to us. The time needed by HCWs was 33 min per patient in the conventional follow-up and 13 min in the electronic follow-up, the total costs per patient being €15.07 and €13.61 respectively. A decrease of 17.1% in annual expenses was achieved with the electronic follow-up. The incidence of HAI was 8.4% in the conventional period and 12.2% in the electronic surveillance period, most cases becoming symptomatic after hospitalization. CONCLUSION: Electronic data collection was a convenient way of implementing a continuous HAI follow-up, achieving both a higher participation rate and lower costs.

Hospital-associated infections in children: a prospective post-discharge follow-up survey in three different paediatric hospitals.

BACKGROUND: Reported viral hospital-associated infection (HAI) frequencies have ranged from 1% to 24% between paediatric wards and hospitals. Reasons for this variation remain unclear. AIM: To evaluate the rate of viral HAIs and risk factors in three different paediatric hospitals. METHODS: Data were collected prospectively for two years in one infectious disease ward and three general paediatric wards in Finland and Switzerland. Infections were recorded during the hospitalization and one week after discharge. Ward-specific risk factors for HAIs within each ward were searched by using multivariate logistic regression analysis. FINDINGS: Altogether 5119 patients were hospitalized. Total HAI frequency was 12.2%, with 2.4% of the patients developing HAI in hospital, most often gastroenteritis, and 9.8% [95% confidence interval (CI): 8.9-10.8%] within 72 h of discharge. HAI rates varied from 5.8% to 17.1% between the wards, the highest rate being in a general paediatric ward where shared rooms were common and active cohorting according to viral aetiology was not done. Shared room (OR: 5.45; 95% CI: 2.44-12.2 in a general ward treating infants), longer hospitalization (OR: 1.42 per day; 95% CI: 1.20-1.67 in an infectious disease ward) and young age (OR: 0.71 per year; 95% CI: 0.51-0.98 in general paediatric ward for children aged >1 year) increased risk of HAI in hospital. CONCLUSION: Most viral HAIs in paediatric wards become evident after discharge. Single room bedding appears to be effective in preventing HAIs, especially the spread of respiratory viruses. It also appears that caring for patients with contagious diseases in a separate unit is advantageous.

Cardiac troponin-I as a screening tool for myocarditis in children hospitalized for viral infection.

AIM: The incidence of myocarditis in children is uncertain because patients with minor symptoms can remain undiagnosed. We hypothesized that screening all children who are hospitalized for an acute infection with troponin-I (TnI) would reveal myocarditis cases and performed a prospective screening study. METHODS: Between October 2005 and July 2008, a blood sample for TnI measurement was taken every time a sample for C-reactive protein measurement was drawn. If TnI value was above the screening limit (0.06 microg/L), electrocardiogram (ECG) and cardiac ultrasound were performed. TnI measurements were repeated until at normal level. RESULTS: Altogether, 1009 children were screened during the 33 months. TnI was above the screening limit (0.06 microg/L) in six children. None of them had any signs of myocarditis in ECG or cardiac ultrasound. Five of those six children were younger than 30 days. All had a respiratory infection as a cause for hospitalization, three of which was caused by RSV. In four children, all younger than 30 days, TnI levels remained high (>0.37 microg/L) for two months, but decreased after that to normal levels. CONCLUSION: The incidence of myocarditis during viral infections is low and a routine TnI screening for asymptomatic myocarditis is not useful.

Biofilm formation by Escherichia coli isolated from patients with urinary tract infections.

AIMS: The significance of biofilm formation for the clinical picture of urinary tract infections (UTI) is largely unknown. We wanted to find out whether Escherichia coli (E. coli) strains isolated from UTI patients differ in their ability to form biofilms and whether this ability is associated with the clinical presentation of UTI. MATERIAL AND METHODS: 70 E. coli strains were isolated from patients with cystitis (43 strains), pyelonephritis (11 strains) and urosepsis (16 strains) and biofilm formation was assessed on polystyrene microtiter plates by measuring the optical density (OD) of the attached material after 72 h of incubation and crystal violet staining of the bacteria. The formation of organized biofilm structures and the viability of the attached bacteria were verified by scanning electron microscopy and confocal scanning laser microscopy in a subsample of 22 strains. RESULTS: 31% of the E. coli strains formed a biofilm. The strains isolated from patients with pyelonephritis had higher ODs than those from patients with cystitis (difference of the means 0.19, 95% confidence limits (CL) 0.06 - 0.32, p = 0.02). The E. coli strains susceptible to antibiotics had higher ODs than the resistant strains (difference of the means 0.21, 95% CL 0.03 - 0.27, p = 0.016). CONCLUSIONS: The ability of bacteria to persist and grow in a biofilm seems to be one of the important factors in both the resistance to antibiotics and the severity of urinary tract inflammation.

Hospital-associated infections during and after care in a paediatric infectious disease ward.

Viruses are important causes of paediatric hospital-associated infections (HAIs). We evaluated the frequency of viral HAIs during hospitalisation and after discharge in a paediatric infection ward. Data were collected prospectively for two years with follow-up questionnaires in which parents reported symptoms of new infections. Infections occurring >72 h after admission to hospital or <72 h after discharge were regarded as hospital-associated. The mean age of patients was 3.0 years and the mean hospitalisation time 3.0 days. Twenty-one out of the 1927 patients [1.1%, 95% confidence interval (CI): 0.7-1.7] developed an HAI during hospitalisation, in every case diarrhoea. A total of 1175 (61%) questionnaires were returned. In all, 86 children (7.3%, 95% CI: 5.9-9.0) had new symptoms within 72 h of discharge, most often diarrhoea (49%). Older age protected against HAI [odds ratio (OR, per year in age): 0.92; 95% CI: 0.85-0.99; P=0.02]. Among the patients hospitalised for respiratory infections, a shared room increased the risk of HAI (OR: 2.3; 95% CI: 1.1-4.8; P=0.03). Eight percent of the patients in our ward, where alcohol hand gel is actively used and single rooms are common, developed an HAI. Eighty percent of the HAIs appeared at home, which emphasises the importance of post-discharge follow-up.

Nasopharyngeal dimensions in magnetic resonance imaging and the risk of acute otitis media.

BACKGROUND: We have previously found by lateral cephalometry an association between nasopharyngeal anatomy and the risk of acute otitis media (AOM). We evaluate here the association of nasopharyngeal dimensions in magnetic resonance imaging (MRI) with the occurrence of AOM in otherwise healthy children. METHODS: Sixty-one healthy children (mean age 5.7 years, range 3.9-6.9) were recruited from child care centres. The parents filled in a questionnaire on the child's history of ear infections and adenoidectomy. MRI was performed with a 4 mm slice thickness during an upper respiratory infection. Five dimensions and two angles expressing the structure of the bony nasopharynx were measured in sagittal images. RESULTS: The dimension from the caudal edge of the septum to the midpoint of the sella, reflecting the height of the nasopharynx, was on average 2.2 mm smaller in the children who had had AOM attacks during the last 12 months than those without attacks (95% confidence interval (CI) 0.9 to 3.4, p=0.001) and the nasal base angle was on average 2.1 degrees smaller (95% CI 0.7 to 3.5, p=0.004). These differences remained significant after adjustment for age, sex and previous adenoidectomy in the logistic modelling. A history of adenoidectomy did not have any effect on the dimensions. CONCLUSIONS: The nasopharynx was smaller in the children with AOM attacks during the last year. The value of this finding for predicting susceptibility to recurrent AOM and directing preventive procedures should be evaluated.

Xylitol concentrations in the saliva of children after chewing xylitol gum or consuming a xylitol mixture.

Xylitol prevents otitis media when given to children regularly five times per day. To find a more convenient dosing schedule, an enzymatic assay was used to measure xylitol concentrations in the saliva of 65 children after giving them xylitol chewing gum or syrup in doses equal to those used in clinical trials. Although concentrations high enough to have an antimicrobial effect were attained, the xylitol disappeared from the saliva within 15 min. This finding indicates that high peak concentrations are more important for efficacy than the amount of time the xylitol concentration exceeds that needed to produce an antimicrobial effect. A schedule with the same single doses given less frequently could be clinically effective in preventing otitis media.

Effect of xylitol on growth of Streptococcus pneumoniae in the presence of fructose and sorbitol.

Xylitol is effective in preventing acute otitis media by inhibiting the growth of Streptococcus pneumoniae. To clarify this inhibition we used fructose, which is known to block similar growth inhibition observed in Streptococcus mutans. In addition, we evaluated the efficacy of sorbitol in inhibiting the growth of pneumococci, as sorbitol is widely used for indications similar to those for which xylitol is used. The addition of 5% xylitol to the growth medium resulted in marked growth inhibition, an effect which was totally eliminated in the presence of 1, 2.5, or 5% fructose but not in the presence of 1 or 5% glucose, 1% galactose, or 1% sucrose. This finding implies that xylitol-induced inhibition of pneumococcal growth is mediated via the fructose phosphotransferase system in a way similar to that in which mutans group streptococcal growth is inhibited. The addition of sorbitol at concentrations of 1, 2.5, or 5% to the growth medium did not affect the growth of pneumococci and neither inhibited nor enhanced the xylitol-induced growth impairment. Thus, it seems that xylitol is the only commercially used sugar substitute proven to have an antimicrobial effect on pneumococci.

Xylitol in preventing acute otitis media.

Xylitol is a polyol sugar alcohol and is referred to as birch sugar, because it can be produced from birch. Natural sources of xylitol include plums, strawberries, raspberries and rowan berries. Xylitol inhibits the growth of Streptococcus pneumoniae and it inhibits the attachment of both pneumococci and Haemophilus influenzae on the nasopharyngeal cells. In two clinical trials xylitol was found efficient to prevent the development of acute otitis media with a daily dose of 8.4-10 g of xylitol given in five divided doses. The efficacy in these 2-3 months follow-up trials was approximately 40% when chewing gum was used and approximately 30% with xylitol syrup. The need to use antimicrobials reduced markedly when using xylitol. In a high-risk group of children with tympanostomy tubes xylitol was ineffective in preventing otitis. Xylitol appears to be an attractive alternative to prevent acute otitis media. A more practical frequency of doses should be found before its use can be widely recommended.

TPA decreases the p53 response to benzo[a]pyrene-DNA adducts in vivo in mouse skin.

TPA, a well-known tumor promoter, decreased the response of nuclear p53 immunoreactivity to benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE)-DNA adducts in C57BL/6 mouse skin in vivo. A dose-dependent increase in both the level of BPDE-DNA adducts and nuclear p53 immunoreactivity was found in mice treated topically with 50-750 microg benzo[a]pyrene. Such a positive correlation between the adducts and p53 positivity was suggested by an earlier study. Since p53 probably functions in DNA damage control, interference by TPA with the p53 response could be a mechanism in TPA-induced tumor promotion. Whether such a mechanism is more general in tumor promotion deserves further study.