Terms used to describe urinary tract infections--the importance of conceptual clarification.

Inaccuracies in medical language are detrimental to communication and statistics in medicine, and thereby to clinical practice, medical science and public health. The purpose of this article is to explore inconsistencies in the use of some medical terms: urinary tract infection, bacteriuria and urethral syndrome. The investigated literature was collected from medical dictionaries, textbooks, and articles indexed in Medline(R). We found various practices regarding how the medical terms should be defined, and had great difficulty in interpreting the status of the statements under the heading of 'definition'. The lesson to be learned, besides a reminder of the importance of clearly defined medical concepts, is that it must be explicitly stated whether what is presented as a definition is to be considered as defining criterion, as recognising criterion or as characteristic of the disease entity.

Using the MEDLINE database to study the concept of urinary tract infections in different domains of medicine.

As a way of exploring differences between medical domains regarding management of urinary tract infections, we investigated the MEDLINE database for differences in indexing patterns. Further, our intention was to assess the MEDLINE database as a source for studying medical domains. We examined the use of main headings, subheadings and the level of main headings in six medical domains that manage urinary tract infections. Many intuitive but also some counterintuitive results were found indicating that the MEDLINE database is difficult to use for studying medical domains mainly due to unclear semantics both in the headings and the indexing process, which results in variability in indexing. This variability probably hides significant results. We also conclude that the differences found indicate that in addition to differences between domains, there are also large variations within domains.

Difficulties for primary health care staff in interpreting bacterial findings on a device for simplified urinary culture.

The reliability of interpretations of findings from dip-slide devices for culturing urine was investigated in a national Swedish external quality assessment (EQA) programme. Also investigated was the extent of improvement in the examination procedure achieved through personnel training programmes and information. According to Swedish national recommendations, dip-slide should only be used in primary health care (PHC) in cases of uncomplicated urinary tract infection (UTI) in females of childbearing age. The recommendations also define six possible outcomes of a dip-slide examination, outcomes that have formed the basis for the EQA programme since 2001. No improvement in ability to classify readings correctly into the six categories was noted for the period 2001 to 2006. Preparations containing 'mixed flora' presented participants with the greatest difficulty, with only 28 % correct reports. The EQA programme, with educational components and voluntary participation, has not improved quality. The disappointing results might be a reflection of the limited effort and resources allocated by clinical microbiology laboratories for training and for sustaining proficiency in the evaluation of dip-slides. For these reasons, we cannot at present recommend the dip-slide technique for use in PHC settings.

Antimicrobial susceptibility pattern of Clostridium difficile and its relation to PCR ribotypes in a Swedish university hospital.

All 238 Clostridium difficile isolates were susceptible to metronidazole and vancomycin, whereas 84% and 1% were resistant to clindamycin and fusidic acid. Etest MICs for metronidazole were lower than agar dilution MICs (P < 0.01) but without difference in susceptible-intermediate-resistant categorization. No particular PCR ribotype was associated with clindamycin or fusidic acid resistance.

Carbon monoxide prevents apoptosis induced by uropathogenic Escherichia coli toxins.

Urinary tract infections (UTIs) are often caused by Escherichia coli (E. coli). Previous studies have demonstrated that up-regulation of heme oxygenase-1 (HO-1) may trigger a survival mechanism against renal cell death induced by E. coli toxins. The present study analyses the role of carbon monoxide (CO), an end product of HO-1, in the survival mechanism. Moreover, we identified hemolysin as a putative pro-apoptotic toxin in the E. coli supernatant. Tubular cells were incubated with CO in the presence or absence of E. coli toxins. Uropathogenic or transformants of non-pathogenic strains expressing hemolysin were used. We found that the survival pathway during E. coli infection might be activated by HO-1-derived production of CO. The protection by CO was also associated with up-regulation of p21 protein expression. Furthermore, we found that in children with pyelonephritis, all the E. coli strains expressing hemolysin induced apoptosis. In E. coli strains not expressing hemolysin, only 45% of the strains could induce apoptosis. In conclusion, generation of CO elicited by HO-1 could promote survival signaling in renal cells. Hemolysin is one of the secreted toxins that are involved in inducing apoptosis during UTI.

Interpreting definitions: the problem of interpreting definitions of medical concepts.

During the last hundred years medical language has been influenced by scientific and technological progress. As a result uncertainty in medical communication is increasing. This may have serious consequences not only for health care delivery but also for medical science. Disease classification, assessment of the validity of epidemiological investigations and comparison of the results of various investigations are examples of what will become less secure. The purpose of the article is to emphasise a main source of uncertainty--the problem of interpreting definitions. Two issues of interpretation are explored. One concerns the logical status of a statement and the other the function of a statement. It is concluded that the security of medical language can be increased through the elucidation of the logical status and functions of statements making up medical concepts.

Biological costs and mechanisms of fosfomycin resistance in Escherichia coli.

Fosfomycin is a cell wall inhibitor used mainly for the treatment of uncomplicated lower urinary tract infections. As shown here, resistance to fosfomycin develops rapidly in Escherichia coli under experimental conditions, but in spite of the relatively high mutation rate in vitro, resistance in clinical isolates is rare. To examine this apparent contradiction, we mathematically modeled the probability of resistance development in the bladder during treatment. The modeling showed that during a typical episode of urinary tract infection, the probability of resistance development was high (>10(-2)). However, if resistance was associated with a reduction in growth rate, the probability of resistance development rapidly decreased. To examine if fosfomycin resistance causes a reduced growth rate, we isolated in vitro and in vivo a set of resistant strains. We determined their resistance mechanisms and examined the effect of the different resistance mutations on bacterial growth in the absence and presence of fosfomycin. The types of mutations found in vitro and in vivo were partly different. Resistance in the mutants isolated in vitro was caused by ptsI, cyaA, glpT, uhpA/T, and unknown mutations, whereas no cyaA or ptsI mutants could be found in vivo. All mutations caused a decreased growth rate both in laboratory medium and in urine, irrespective of the absence or presence of fosfomycin. According to the mathematical model, the reduced growth rate of the resistant strains will prevent them from establishing in the bladder, which could explain why fosfomycin resistance remains rare in clinical isolates.

Performance of four chromogenic urine culture media after one or two days of incubation compared with reference media.

Four chromogenic urine culture media were compared to culture on blood agar, MacConkey agar, and CLED (cysteine-, lactose-, and electrolyte-deficient) agar for detection of uropathogens in 1,200 urine specimens. After 2 nights of incubation, 96% of all isolates were recovered on blood agar, 96% were recovered on CLED agar, 92% were recovered on CPS ID2, 96% were recovered on CHROMagar Orientation from BBL, 95% were recovered on CHROMagar Orientation from The CHROMagar Company, and 95% were recovered on Chromogenic UTI Medium.

Activation of extracellular signal-regulated kinase mediates apoptosis induced by uropathogenic Escherichia coli toxins via nitric oxide synthase: protective role of heme oxygenase-1.

Pyelonephritis is a risk factor for renal tubular epithelial cell damage in children. The inter- and intracellular regulator nitric oxide (NO) plays a role in the modulation of cellular viability in urinary tract infections, but the role of the NO pathway in renal proximal tubular-cell death remains unclear. The present study demonstrates that, in renal epithelial cells undergoing death mediated by Escherichia coli strain ARD6 serotype O6K13H1 (O6), levels of the phosphorylated extracellular signal-regulated kinase (ERK) 1/2 and inducible NO synthase (iNOS) proteins are up-regulated, but levels of endothelial NO synthase are down-regulated. When NO synthase (NOS) activity is inhibited by the specific inhibitor of NOS or mitogen-activated protein kinase kinase, cells are prevented from death. Moreover, down-regulating protein 53 (p53) does not prevent the cells from dying, although p53 is up-regulated in O6-exposed cells. Up-regulation of heme oxygenase (HO)-1 by sodium nitroprusside or by the specific activator hemin inhibits cell death. In conclusion, the activation of ERK mediates O6 toxin-mediated renal cell death via induction of iNOS. Stimulation of HO-1 protects cells against death.