Presentation, pattern, and natural course of severe symptoms, and role of antibiotics and antibiotic resistance among patients presenting with suspected uncomplicated urinary tract infection in primary care: observational study.

OBJECTIVE: To assess the natural course and the important predictors of severe symptoms in urinary tract infection and the effect of antibiotics and antibiotic resistance. DESIGN: Observational study. SETTING: Primary care. PARTICIPANTS: 839 non-pregnant adult women aged 18-70 presenting with suspected urinary tract infection. MAIN OUTCOME MEASURE: Duration and severity of symptoms. RESULTS: 684 women provided some information on symptoms; 511 had both laboratory results and complete symptom diaries. For women with infections sensitive to antibiotics, severe symptoms, rated as a moderately bad problem or worse, lasted 3.32 days on average. After adjustment for other predictors, moderately bad symptoms lasted 56% longer (incidence rate ratio 1.56, 95% confidence interval 1.22 to 1.99, P<0.001) in women with resistant infections; 62% longer (1.62, 1.13 to 2.31, P=0.008) when no antibiotics prescribed; and 33% longer (1.33, 1.14 to 1.56, P<0.001) in women with urethral syndrome. The duration of symptoms was shorter if the doctor was perceived to be positive about diagnosis and prognosis (continuous 7 point scale: 0.91, 0.84 to 0.99; P=0.021) and longer when the woman had frequent somatic symptoms (1.03, 1.01 to 1.05, P=0.002; for each symptom), a history of cystitis, urinary frequency, and more severe symptoms at baseline. CONCLUSION: Antibiotic resistance and not prescribing antibiotics are associated with a greater than 50% increase in the duration of more severe symptoms in women with uncomplicated urinary tract infection. Women with a history of cystitis, frequent somatic symptoms (high somatisation), and severe symptoms at baseline can be given realistic advice that they are likely to have severe symptoms lasting longer than three days.

Effectiveness of five different approaches in management of urinary tract infection: randomised controlled trial.

OBJECTIVE: To assess the impact of different management strategies in urinary tract infections. DESIGN: Randomised controlled trial. SETTING: Primary care. PARTICIPANTS: 309 non-pregnant women aged 18-70 presenting with suspected urinary tract infection. INTERVENTION: Patients were randomised to five management approaches: empirical antibiotics; empirical delayed (by 48 hours) antibiotics; or targeted antibiotics based on a symptom score (two or more of urine cloudiness, urine smell, nocturia, or dysuria), a dipstick result (nitrite or both leucocytes and blood), or a positive result on midstream urine analysis. Self help advice was controlled in each group. MAIN OUTCOME MEASURES: Symptom severity (days 2 to 4) and duration, and use of antibiotics. RESULTS: Patients had 3.5 days of moderately bad symptoms if they took antibiotics immediately. There were no significant differences in duration or severity of symptoms (mean frequency of symptoms on a 0 to 6 scale: immediate antibiotics 2.15, midstream urine 2.08, dipstick 1.74, symptom score 1.77, delayed antibiotics 2.11; likelihood ratio test for the five groups P=0.177). There were differences in antibiotic use (immediate antibiotics 97%, midstream urine 81%, dipstick 80%, symptom score 90%, delayed antibiotics 77%; P=0.011) and in sending midstream urine samples (immediate antibiotics 23%, midstream urine 89%, dipstick 36%, symptom score 33%, delayed antibiotics 15%; P<0.001). Patients who waited at least 48 hours to start taking antibiotics reconsulted less (hazard ratio 0.57 (95% confidence interval 0.36 to 0.89), P=0.014) but on average had symptoms for 37% longer than those taking immediate antibiotics (incident rate ratio 1.37 (1.11 to 1.68), P=0.003), particularly the midstream urine group (73% longer, 22% to 140%; none of the other groups had more than 22% longer duration). CONCLUSION: All management strategies achieve similar symptom control. There is no advantage in routinely sending midstream urine samples for testing, and antibiotics targeted with dipstick tests with a delayed prescription as backup, or empirical delayed prescription, can help to reduce antibiotic use. STUDY REGISTRATION: National Research Register N0484094184 ISRCTN: 03525333.

Dipsticks and diagnostic algorithms in urinary tract infection: development and validation, randomised trial, economic analysis, observational cohort and qualitative study.

OBJECTIVES: To estimate clinical and dipstick predictors of infection and develop and test clinical scores; to compare management using clinical and dipstick scores with commonly used alternative strategies; to estimate the cost-effectiveness of each strategy; and to understand the natural history of urinary tract infection (UTI) and women's concerns about its presentation and management. DESIGN: There were six studies: (1) validation development for diagnostic clinical and dipstick scores; (2) validation of the scores developed; (3) observation of the natural history of UTI; (4) randomised controlled trial (RCT) of scores developed in study 1; (5) economic analysis of the RCT; (6) qualitative study of patients in the RCT. SETTING: Primary care. PARTICIPANTS: Women aged 17-70 with suspected UTI. INTERVENTIONS: Patients were randomised to five management approaches: empirical antibiotics; empirical delayed antibiotics; target antibiotics based on a higher symptom score; target antibiotics based on dipstick results; or target antibiotics based on a positive mid-stream specimen of urine (MSU). MAIN OUTCOME MEASURES: Antibiotic use, use of MSUs, rates of reconsultation and duration, and severity of symptoms. RESULTS: (1) 62.5% of women had confirmed UTI. Only nitrite, leucocyte esterase and blood independently predicted diagnosis of UTI. A dipstick rule--based on having nitrite or both leucocytes and blood--was moderately sensitive (77%) and specific (70%) [positive predictive value (PPV) 81%, negative predictive value (NPV) 65%]. A clinical rule--based on having two of urine cloudiness, offensive smell, reported moderately severe dysuria, moderately severe nocturia--was less sensitive (65%) (specificity 69%, PPV 77%, NPV 54%). (2) 66% of women had confirmed UTI. The predictive values of nitrite, leucocyte esterase and blood were confirmed. The dipstick rule was moderately sensitive (75%) but less specific (66%) (PPV 81%, NPV 57%). (3) Symptoms rated as moderately bad or worse lasted 3.25 days on average for infections sensitive to antibiotics; resistant infections lasted 56% longer, infections not treated with antibiotics 62% longer and symptoms associated with urethral syndrome 33% longer. Symptom duration was shorter if the doctor was perceived to be positive about prognosis, and longer with frequent somatic symptoms, previous history of cystitis, urinary frequency and more severe symptoms at baseline. (4) 66% of the MSU group had laboratory-confirmed UTI. Women suffered 3.5 days of moderately bad symptoms if they took antibiotics immediately but 4.8 days if they delayed taking antibiotics for 48 hours. Taking bicarbonate or cranberry juice had no effect. (5) The MSU group was more costly over 1 month but not over 1 year. Cost-effectiveness acceptability curves showed that for a value per day of moderately bad symptoms of over 10 pounds, the dipstick strategy is most likely to be cost-effective. (6) Fear of spread to the kidneys, blood in the urine, and the impact of symptoms on vocational and leisure activities were important triggers for seeking help. When patients are asked to delay taking antibiotics the uncomfortable and worrying journey from 'person to patient' needs to be acknowledged and the rationale behind delaying the antibiotics made clear. CONCLUSIONS: To achieve good symptom control and reduce antibiotic use clinicians should either offer a 48-hour delayed antibiotic prescription to be used at the patient's discretion or target antibiotic treatment by dipsticks (positive nitrite or positive leucocytes and blood) with the offer of a delayed prescription if dipstick results are negative.

Community and hospital spread of Escherichia coli producing CTX-M extended-spectrum beta-lactamases in the UK.

OBJECTIVES: During 2003, the Health Protection Agency's Antibiotic Resistance Monitoring and Reference Laboratory began to receive isolates of Escherichia coli for confirmation of extended-spectrum beta-lactamase production with a phenotype implying a CTX-M-type beta-lactamase, i.e. MICs of cefotaxime > or = 8-fold higher than MICs of ceftazidime. Many were referred as being from community patients. We examined 291 CTX-M-producing isolates from the UK and investigated the genetic basis of their phenotype. METHODS: PCR was used to detect alleles encoding CTX-M enzymes and to assign these to their blaCTX-M phylogenetic groups. Selected alleles were sequenced. Producers were compared by analysis of banding patterns generated by pulsed-field gel electrophoresis of XbaI-digested genomic DNA. MICs were determined by an agar dilution method or by Etest. RESULTS: Of 291 CTX-M-producing E. coli isolates studied from 42 UK centres, 70 (24%) were reportedly from community patients, many of whom had only limited recent hospital contact. Community isolates were referred by 12 centres. Two hundred and seventy-nine (95.9%) producers contained genes encoding group 1 CTX-M enzymes and 12 contained blaCTX-M-9-like alleles. An epidemic CTX-M-15-producing strain was identified, with 110 community and inpatient isolates referred from six centres. Representatives of four other major strains also produced CTX-M-15, as did several sporadic isolates examined. Most producers were multi-resistant to fluoroquinolones, trimethoprim, tetracycline and aminoglycosides as well as to non-carbapenem beta-lactams. CONCLUSIONS: CTX-M-producing E. coli are a rapidly developing problem in the UK, with CTX-M-15 particularly common. The diversity of producers and geographical scatter of referring laboratories indicates wide dissemination of blaCTX-M genes. Because of the public health implications, including for the treatment of community-acquired urinary tract infections, the spread of these strains--and CTX-M-15 beta-lactamase in particular--merits close monitoring.

Surgery for active culture-positive endocarditis: determinants of early and late outcome.

BACKGROUND: The purpose of this study was to describe a single unit experience in the surgical treatment of active culture-positive endocarditis and identify determinants of early and late outcome. PATIENTS AND METHODS: One hundred eighteen consecutive patients with positive blood culture up to 3 weeks before operation (or positive valve culture) and macroscopic evidence of lesions typical for endocarditis, undergoing operation between January 1973 and December 1996 in Southampton, were evaluated. The aortic valve was infected in 53 (48.9%), the mitral in 46 (39%), both aortic and mitral in 12 (10.1%), the tricuspid in 4 (3.9%), and the pulmonary valve in 3 (2.5%). Native valve endocarditis was present in 83 (70.3%) and prosthetic valve endocarditis in 35 (29.7%). Streptococci and staphylococci were the most common pathogens. Mean follow-up was 5.6 years (range, 0 to 25 years). RESULTS: Operative mortality was 7.6% (9 patients). Endocarditis recurred in 8 (6.7%). A reoperation was required in 12 (10.2%). There was 24 late deaths, 17 of them cardiac. Actuarial freedom from recurrent endocarditis, reoperation, late cardiac death, and long-term survival at 10 years were 85.9%, 87.2%, 85.2%, and 73.1%, respectively. On multiple regression analysis the following were independent adverse predictors: pulmonary edema (p = 0.007) and impaired left ventricular function (p = 0.02) for operative mortality; prosthetic valve endocarditis (p = 0.01) for recurrent infection; myocardial invasion by the infection (p = 0.01) and reoperation (p = 0.04) for late cardiac death; and coagulase-negative staphylococcus (p = 0.02), annular abscess (p = 0.02), and longer intensive care unit stay (p = 0.02) for long-term survival. CONCLUSIONS: Operation for active culture-positive endocarditis carries an acceptable mortality. Freedom from recurrent infection, reoperation, and long-term survival are satisfactory. In our data, patients' hemodynamic status at operation was the major determinant of operative mortality. Prosthetic valve endocarditis, coagulase-negative staphylococcus, and annular or myocardial infectious invasion were the critical adverse determinants of late outcome.

The systemic inflammatory response syndrome as a predictor of bacteraemia and outcome from sepsis.

Criteria defining the systemic inflammatory response syndrome (SIRS) were used to assess prospectively 270 clinical episodes in which blood cultures were taken from patients in general medicine. SIRS, severe sepsis and septic shock occurred in 149 (55%), 13 (5%) and 9 (3%) episodes, respectively. However, evidence of organ hypoperfusion indicating severe sepsis was recorded as sought in only 26% of episodes of SIRS. Crude mortality at 28 days increased sequentially as more SIRS criteria were met, rising from 12% in non-SIRS blood culture episodes, to 36% when all four criteria were met. Mortality from severe sepsis and septic shock was 38% and 56%, respectively. In 61/64 (95%) episodes of clinically important bacteraemia, patients fulfilled SIRS criteria when the blood culture was taken. However, the positive predictive value of SIRS for predicting bacteraemia was only 7%. Patients who did not fulfil SIRS criteria when blood cultures were taken were at low risk of bacteraemia and comprised 45% (121/270) of the study population. Three patients in this low-risk group had bacteraemia. Mortality in bacteraemic patients with severe sepsis or septic shock who were initially treated with ineffective antibiotics for up to 48 h was 80%, compared to 42% in those always treated appropriately.

An atypical case of Corynebacterium diphtheriae endocarditis and subsequent outbreak control measures.

An atypical case of Corynebacterium diphtheriae endocarditis with severe rhabdomyolysis and cerebral emboli is presented. The patient underwent successful mitral and aortic valve replacements and is only the third reported case with a successful outcome following surgery. Outbreak control measures were complicated by an equivocal result from guinea pig toxin tests.

Polymerase chain reaction detection of small round-structured viruses from two related hospital outbreaks of gastroenteritis using inosine-containing primers.

Two outbreaks of gastroenteritis in the UK which occurred nine days apart at Lymington and Southampton hospitals were investigated. The clinical and epidemiological features of both outbreaks were characteristic of small round-structured virus (SRSV) infection with rapid onset of diarrhoea and/or nausea and vomiting and propagation of the outbreaks by secondary spread. SRSV particles were observed by immune electron microscopy (EM) in 60% of faecal samples from both outbreaks and no other pathogens were detected. The index case for the second outbreak was a patient who was admitted with diarrhoea and vomiting after being discharged from Lymington hospital during the first outbreak. The possibility that the two outbreaks were caused by the same strain of SRSV was investigated by the polymerase chain reaction (PCR). New inosine-containing PCR primers were designed to amplify the RNA polymerase region of SRSV cDNA from genetic groups I and II. The PCR using the group II primers achieved a higher detection rate for SRSVs in faecal samples (68% of samples positive from both outbreaks) than immune EM. SRSVs were not detected using the group I primers or using conventional degenerate PCR primers. The nucleotide sequences of PCR amplicons from both outbreaks were identical providing molecular epidemiological evidence for the involvement of a single SRSV strain. Comparison of the RNA polymerase region of this virus with the equivalent regions of genetic group I (69.4-75.0% amino acid identify) and genetic group II (88.9-100% amino acid and 77.1-88.1% nucleotide identity) SRSVs revealed that the causative SRSV was a distinct member of genetic group II.

Prevention of sepsis following endoscopic retrograde cholangiopancreatography.

Ora; ciprofloxacin was studied as a prophylactic antimicrobial agent in high- and low-risk patients undergoing endoscopic retrograde cholangiography. Ciprofloxacin appeared to be effective, good serum levels were attained, and the drug compared favourably on grounds of cost and convenience with a parenterally-administered cephalosporin.

Antibiotic exposure delays intestinal colonization by Clostridium difficile in the newborn.

Two antibiotic regimens commonly used in neonatal intensive care were compared for the rate at which Clostridium difficile appeared in the faeces. Over a nine month period neonates with suspected sepsis admitted to a Special Care Baby Unit (SCBU) were randomly allocated to receive either cefotaxime or penicillin and netilmicin. A contemporaneous group also admitted to SCBU but without sepsis served as non-treated controls. Four hundred and sixteen stool specimens from 158 neonates without diarrhoea were analysed every five to seven days until discharge. The results showed that these antibiotics did not encourage gut colonization by C. difficile, that they might even be protective in this respect and that monotherapy with cefotaxime was no more likely to generate C. difficile overgrowth than the penicillin-aminoglycoside regimen.

Carbohydrate fermentation by gut microflora in preterm neonates.

To study organic acid excretion, urine was collected from 52 preterm infants at weekly intervals and analysed by capillary gas chromatography-mass spectrometry. Twelve of 22 babies born before 33 weeks' gestation excreted 2,3-butanediol, as did six born between 33 and 36 weeks. Six very immature babies also excreted acetoin, the metabolic precursor of the diol. Other products derived from carbohydrate included methylmalonic and ethylmalonic acids in one baby, and D-lactic acid in five. Acetoin has never been found in urine before, and the other four acids have been found only rarely. Excretion of these metabolites by preterm babies can be explained by increased intestinal permeability, unabsorbed lactose in the colon, and colonisation with certain opportunistic micro-organisms prevalent in neonatal units, including klebsiella, serratia, and enterobacter. The findings support evidence from breath hydrogen analysis that carbohydrate fermentation takes place in the gut of preterm infants.

Neonatal renal function assessment.

Urine samples from neonates admitted to a special care baby unit were analysed to establish ranges for urinary retinol binding protein, albumin, and total protein concentrations in healthy term and preterm infants and to investigate changes seen in disease states. Urinary excretion of retinol binding protein was greater in preterm infants and was increased in sick infants. This was greater than would be predicted from changes in creatinine excretion with gestational or postconceptional age. Urinary retinol binding protein appeared more sensitive to illness than did urinary albumin or total protein.

A randomised prospective comparison of cefotaxime versus netilmicin/penicillin for treatment of suspected neonatal sepsis.

In an open prospective study performed in 2 neonatal units, infants with suspected neonatal sepsis (SNS) of unknown microbial cause were randomly allocated to receive treatment with either cefotaxime (CTX) or netilmicin plus penicillin (N + P). 236 patients were entered into the trial, of whom 222 were evaluable. The number of 'definitely' and 'probably' infected babies was similar in both groups. There was no difference in clinical outcome between patients in the 2 treatment groups and no side effects were recorded for either of the antibiotic regimens. Antibiotic sensitivity testing of bacterial isolates from peripheral sites showed almost universal sensitivity of potential pathogens to both antibiotic regimens at the start of treatment in all infants. Thereafter, organisms resistant to CTX were isolated from patients in both treatment groups, possibly reflecting the antibiotic sensitivity profile of the colonising bacteria in both neonatal units. The results of this study indicate that either CTX or N + P are suitable, in our units, for the 'blind' treatment of early SNS. In units where listerial infections are prevalent, specific cover should be added to CTX. For SNS developing after admission, the choice of antibiotics will depend upon the background antibiotic sensitivity profile of the colonising bacteria.

Skin rash associated with Candida guilliermondii.

We report a case in which the development of a skin rash in a neutropenic patient was associated with multiple blood culture isolates of Candida guilliermondii--an unusual isolate not previously documented to cause rashes.

A hospital outbreak caused by a chlorhexidine and antibiotic-resistant Proteus mirabilis.

An outbreak of urinary-tract infection involving a strain of Proteus mirabilis resistant to gentamicin and several other antibiotics affected 90 patients in Southampton between July 1980 and May 1985. The outbreak strain was also resistant to chlorhexidine and this, in combination with the antibiogram and Dienes' test, permitted differentiation from other P. mirabilis strains. The outbreak had features in common with other Enterobacteriaceae outbreaks, although certain aspects of the population involved have made it particularly difficult to control. The outbreak commenced shortly after the introduction of a catheter care policy which involved the use of chlorhexidine, and although the majority of the cases were colonized before this policy was enforced, chlorhexidine had been used extensively for other procedures within the district. Preliminary evidence suggests that there is no genetic linkage between the chlorhexidine and multiple antibiotic resistance.

An outbreak of gastroenteritis on a passenger cruise ship.

In an outbreak of gastroenteritis on board a cruise ship 251 passengers and 51 crew were affected and consulted the ship's surgeon during a 14-day period. There was a significant association between consumption of cabin tap water and reported illness in passengers. Enterotoxigenic Escherichia coli were isolated from passengers and crew and coliforms were found in the main water storage tank. Contamination of inadequately chlorinated water by sewage was the most likely source of infection. A low level of reported illness and late recognition of the outbreak delayed investigation of what was probably the latest in a series of outbreaks of gastrointestinal illness on board this ship. There is a need for a national surveillance programme which would monitor the extent of illness on board passenger cruise ships as well as a standard approach to the action taken when levels of reported illness rise above a defined level.

An investigation into in vitro methods for the detection of chlorhexidine resistance.

During an outbreak of catheter-related urinary tract infection, due to Proteus mirabilis, it was suggested that the epidemic strain was resistant to chlorhexidine. In this study, the minimum inhibitory concentrations (MICs) of chlorhexidine to the epidemic Pr. mirabilis and other laboratory isolates were tested in different media. Results were compared with killing times using 1/4 strength Ringers solution, normal human urine and the in vivo killing times in two patients' catheter bags. It was found that the MIC test was unreliable in the assessment of chlorhexidine resistance as it was dependent on the medium used, the inoculum size, and the age of the culture. The test which gave results closest to the in vivo experiments was the killing curve in normal human urine. It is concluded that chlorhexidine resistance is a complex phenomenon which is difficult to evaluate. If in vitro tests are to be used to evaluate the clinical relevance of reduced sensitivity to chlorhexidine, they must mimic the in-use conditions as closely as possible.