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Pivmecillinam (amdinocillin pivoxil) is the recommended first‐choice antibiotic used to treat urinary tract infections (UTIs) in Denmark. The frequency of mutation to mecillinam (MEC) resistance is described as high in vitro; however, treatment of UTI has a good clinical response and prevalence of mecillinam resistance in Escherichia coli remains low despite many years of use. We describe occurrence of in vivo mecillinam resistance in a clinical isolate of ESBL‐producing E. coli following pivmecillinam treatment. The identified phenotypic differences in the mecillinam resistant isolate compared with the original mecillinam susceptible isolate were a full‐length LPS with O‐antigen (O25), mecillinam resistance and a lower MIC for ceftazidime. Regarding genotype, the resistant isolate differed with a mutation in bla CTX‐M‐15 to bla CTX‐M‐127, loss of a part of a plasmid and a genomic island, respectively, and insertion of a transposase in wbbL, causing the rough phenotype. The observed mecillinam resistance is expected to be caused by the mutation in bla CTX‐M‐15 with additional contribute from the serotype shift. We continue to recommend the use of pivmecillinam as first‐line treatment for UTI., In this study, we investigated the genetics behind mecillinam resistance which occurred in an extended‐spectrum β‐lactamase‐producing Escherichia coli during pivmecillinam treatment of a patient. The genomic comparison of the two isolates points toward a mutational change of blaCTX‐M‐15 into blaCTX‐M‐127 along with a serotype shift from rough to full‐length O25 as the mechanisms contributing to the change in mecillinam susceptibility.

BACKGROUND: The Danish Hospital-Acquired Infections Database (HAIBA) is an automated surveillance system using hospital administrative, microbiological, and antibiotic medication data.AIM: To define and evaluate the case definition for hospital-acquired urinary tract infection (HA-UTI) and to describe surveillance data from 2010 to 2014.METHODS: The HA-UTI algorithm defined a laboratory-diagnosed UTI as a urine culture positive for no more than two micro-organisms with at least one at ≥10(4)cfu/mL, and a probable UTI as a negative urine culture and a relevant diagnosis code or antibiotic treatment. UTI was considered hospital-acquired if a urine sample was collected ≥48h after admission and FINDINGS: HAIBA detected a national incidence rate of 42.2 laboratory-diagnosed HA-UTI per 10,000 risk-days with an increasing trend. Compared to PPS the laboratory-diagnosed HA-UTI algorithm had a sensitivity of 50.0% (26/52) and a specificity of 94.2% (1842/1955). There were several reasons for discrepancies between HAIBA and PPS, including laboratory results being unavailable at the time of the survey, the results considered clinically irrelevant by the surveyor due to an indwelling urinary catheter or lack of clinical signs of infection, and UTIs being considered HA-UTI in PPS even though the first sample was taken within 48h of admission.CONCLUSION: The HAIBA algorithm was found to give valid and valuable information and has, among others, the advantages of covering the whole population and allowing continuous standardized monitoring of HA-UTI.

Adherence of 18 staphylococcal strains to 13 types of uncoated plastic tubes made from 10 different plastic materials were investigated by binding of radiolabelled bacteria in phosphate-buffered saline for 2 h at 37 degrees C. The different materials could be divided into five groups based on their ability to bind staphylococci. Lowest adhesion was found for plasticised polyvinylchloride. Simple assays for the relative binding of peroxidase-labelled human IgG or fibrinogen did not predict the result of adhesion studies. Neither bacterial surface hydrophobicity measured in a two-phase partitioning assay, nor hydrophobicity of materials (wettability) as measured by their contact angles in water correlated with bacterial adhesion. Adhesion of staphylococci to certain plastic materials was greatly influenced by the method used for sterilisation of the material.

European Council resolutions on tattoo ink introduce sterility and preservation of inks to protect customers. Inks used in Denmark are typically purchased over the internet from international suppliers and manufacturers from the US and the UK. In Denmark tattoo inks are regulated and labelled according to REACH as if they were plain chemicals.The objective of this study was to check the microbial product safety of unopened and opened tattoo ink stock bottles. Packaging, labelling, preservation, sterility and contamination with micro-organisms were studied.Physical inspection and culture of bacteria and fungi.Six of 58 unopened stock bottles (10%) were contaminated with bacteria and one of six samples (17%) of previously used stock bottles was contaminated. The bacterial species represented bacteria considered pathogenic in humans as well as non-pathogenic environmental bacteria. Yeast or moulds were detected in none of the samples. A total of 31% of the manufacturers informed only about the brand name. No information about content, sterility, risks or expiry date was indicated on the label. A total of 42% claimed sterility of their inks. A total of 54% labelled a maximum period of durability of typically 2-3 years. The physical sealing was leaking in 28% of the products.The European Council resolutions regarding safety of tattoo inks are not effective. Stock bottles of tattoo ink may contain bacteria pathogenic to humans and environmental bacteria, and packaging, labelling and preservation of inks are of inadequate quality. Claim of sterility can be erroneous.

BACKGROUND: Pleural empyema is a well known complication of pneumonia. Attitudes differ, however, about the best treatment of this condition and the place of drainage, early operation, and local antibiotics. METHODS: In a retrospective study 94 consecutive patients with verified empyema caused by pneumonia were admitted to the department of either pulmonary medicine or thoracic surgery. Treatment was either by a lavage regimen (daily thoracocentesis, saline rinse, systemic antibiotics, and in some patients instillation of local antibiotics) in the medical ward (51 patients) or by tube drainage and systemic antibiotics in the surgical unit (43 patients). RESULTS: The stay in hospital was significantly shorter in the medically treated patients than in the surgical group--2.3 v 5.0 weeks respectively. Furthermore, pleurocutaneous and bronchopleural fistulas developed more frequently in patients treated by tube drainage than in those treated with the thoracocentesis regimen alone (13 (30%) v 5 (10%) and 6 (14%) v 2 (4%) for each complication respectively). The overall mortality was 8.5% with no differences between treatments. CONCLUSIONS: Treatment with a lavage regimen plus local and systemic antibiotics seems to be associated with a lower frequency of complications and a shorter duration of hospital stay than tube drainage and systemic antibiotics. These results should be confirmed by a prospective, randomised study.

Summary Background Staphylococcus aureus in atopic skin has been associated with exacerbation of eczema. Objectives To investigate a possible association between neonatal colonization with S. aureus and the risk of atopic dermatitis (AD) during the first 3 years of life. Materials and methods The study participants were 356 children born of mothers with asthma from the Copenhagen Prospective Study on Asthma in Childhood. Swabs from the vestibulum nasi and the perineum were cultured at 1 month and 1 year, from acute eczema, and from parents (vestibulum nasi and pharynx). AD development and severity were monitored prospectively. Results Of the neonates, 5·3% had positive swabs for S. aureus cultured from the vestibulum nasi (51·3%) and/or the perineum (11·3%). Forty-two per cent developed AD, but without association between colonization with S. aureus at 1 month of age and risk of developing AD at 3 years of age. There was a 70% concordance for S. aureus carriage between neonates and parents. At 1 year of age 11·3% children had swabs positive for S. aureus. Fourteen per cent of children tested at the 1-year visit developed AD after the visit but before 3 years of age, but again, there was no association between colonization with S. aureus and the risk of AD. In children seen at acute visits the severity of AD measured by scoring of atopic dermatitis (SCORAD) was significantly higher in children with a positive culture for S. aureus in lesions. Conclusions Colonization with S. aureus at 1 month of age is not associated with an increased risk of developing AD during the first 3 years of life.

The aim was to study whether an audit of treatment of infections in general practice resulted in changed prescribing habits. In 1995-1996 forty-six general practitioners (GP's) from the County of Roskilde participated in an audit regarding infectious diseases (incl. course participation and preparation of treatment guidelines). The effect evaluation was done on the basis of 1) two self-registrations of antibiotic prescriptions carried out with one year's interval, and 2) prescribing data from the National Insurance database collected over two periods, before the first and second self-registration respectively. The number of patients not receiving antibiotics increased significantly from 47.2% to 52.4% after intervention. The self-registration did not show any change in choice of antibiotics, while the registry data showed a shift from broad-spectrum to narrow-spectrum penicillin. This change was, however, also found among the GP's, who did not participate in the audit. The study demonstrated that audit can result in changes in prescribing patterns, but at the same time emphasizes the need for inclusion of external data sources and control groups in the evaluation of intervention effects.

Ciprofloxacin 500 mg orally twice daily was compared to pivampicillin 700 mg orally twice daily for 10 days in 172 men (41-85 years) with acute epididymitis. Failure of treatment occurred in 48 patients, in 15/76 (19.7%) receiving ciprofloxacin versus in 33/82 (40.2%) receiving pivampicillin (p = 0.006). Ciprofloxacin 500 mg orally twice daily is more effective than pivampicillin 700 mg orally twice daily and has fewer adverse events.

The central S. aureus surveillance in Denmark made it possible to analyze the clinical features of S. aureus endocarditis in a nation-wide population of non-drug addicts. Almost all cases of bacteraemia with S. aureus are reported to the Staphylococcus laboratory, Copenhagen. The medical records were reviewed in cases from 1982 to 1991 in which the diagnosis of endocarditis was reported or suspected. Two hundred and sixty patients fulfilled the diagnostic criteria. In 83 patients the diagnosis of endocarditis was not suspected clinically. The overall mortality rate among those patients whose disease was diagnosed clinically was 46% and significantly associated with late congestive heart failure, age and involvement of the central nervous system. A more frequent use of echocardiography as a screening method seems essential to improve the prognosis of patients with S. aureus endocarditis. Involvement of the CNS constitutes a relative indication for early valve replacement.

To compare the efficacy and safety of ciprofloxacin 500 mg orally twice daily with pivampicillin 700 mg orally twice daily for 10 days in men with acute epididymitis and over 40 years of age.The study comprised 172 men who entered a prospective, controlled, randomized, double-blind, trial of pivampicillin and ciprofloxacin. The median (range) age of the 158 patients eligible for the efficacy analysis was 58 (41-85) years; 41% had previously had a urinary tract infection and 27% had previously had epididymitis. Only one patient had a urethral catheter and 38% were sexually active. About half of the patients were admitted to hospital.No bacteria could be cultured from samples in 53% of the patients; Escherichia coli could be cultured from 35% and the remaining isolates were the expected urinary pathogens. None of the patients had Gonococci and only one in each group had Chlamydia. Mycoplasma hominis was detected in three patients only and M. genitalium was detected in three, while Ureaplasma was detected in 24 (15%). The treatment failed in 48 patients; in 15 of 76 (20%) receiving ciprofloxacin and in 33 of 82 (40%) receiving pivampicillin. This corresponds to a reduction in the risk of failure of 20.5% (95% confidence limits 6.6-40.2%, P=0. 006). The principal cause of failure was an unsatisfactory clinical response requiring changed antibiotic treatment in 27 patients; adverse events were responsible for failure in 14. The in vitro resistance of cultured bacteria was low in both groups, at approximately 4%. Adverse events, mainly gastro-intestinal, occurred in 17 of 83 (21%) patients starting on ciprofloxacin and in 33 of 89 (37%) receiving pivampicillin (P=0.04).For epididymitis in men over the age of 40 years ciprofloxacin 500 mg orally twice daily is more effective than pivampicillin 700 mg orally twice daily. Furthermore, ciprofloxacin has a lower incidence of adverse events.

The purpose of the study was to evaluate the effect and side-effects of once daily (OD) administration of gentamicin. The study was a retrospective analysis of patients treated with gentamicin OD for at least two days for proven or suspected infection. Of the 101 patients included, 60 were female, and the median age was 64 years (range: 20-90 years). Median duration of treatment was six days (2-63 days). All patients received combination therapy with two (36 patients), three (64 patients) or four (one patient) antibiotics, apart from gentamicin usually ampicillin, cefuroxime and/or metronidazole. Gentamicin doses were usually 240 mg on a fixed basis, but reduced in patients with pre-treatment impairment of serum-creatinine. Bacteriological cultures were taken in 90% of the patients, of which 59% were positive, most often with Enterobacteriaceae (57%) or other Gram-negative rods (11%). Effect of antibiotic treatment was seen in 82% of the patients. Nephrotoxicity defined as a 44 umol/l increase in serum-creatinine during treatment was found in five patients (5%). Ototoxicity, i.e. clinical signs of tinnitus, dizziness and/or impaired hearing, was reported in two patients. In conclusion, gentamicin OD with 240 mg is easy to administer, appears to be sufficient with regard to effect and has a low frequency of side-effects.

The clinical manifestations and epidemiological data of 11 patients infected with Vibrio vulnificus found in Denmark during the unusually warm summer of 1994 are reported. All patients had been exposed to seawater prior to illness, but none had consumed seafood. Nine patients, including four with bacteraemia, developed skin manifestations of various degrees of severity. One patient died of septic shock despite surgery and treatment with relevant antibiotics. Four patients contracted the disease while fishing. High seawater temperature increases the risk of V. vulnificus infections even in temperate climates such as the Danish. Exposure to seawater, including handling of fresh seafood, during warm periods carries a risk of infection with V. vulnificus.

Despite of extensive use of antibiotics for respiratory tract infections pleural empyema is still seen as a complication to pneumonia (7-10 cases/100.000 inhabitants pr. year). Pleural empyema as a complication to pulmonary surgery is reported in 2-3% of the patients even with use of antibiotic prophylaxis. Pleural empyema is most often a serious disease of long duration. The diagnosis is obtained with microbiological and histological examination of the pleural fluid. Mixed infection occurs in over half of the cases, most often including anaerobic bacteria, but most human pathogens have been reported as etiological agents. Treatment includes drainage of pus and administration of relevant antibiotics, systemically and pleurally. Drainage can be performed via thoracocentesis, by tubes, or by resection of a part of the rib. The optimal treatment strategy is so far unknown, since good prospective comparative clinical studies are lacking.

The number of Staphylococcus aureus bacteremia cases has increased annually in Denmark during the latest decades. This increase has occurred among older patients with hospital-acquired bacteremia. Methicillin-resistance, which earlier was a property of strains of the 83A phage-complex, has nearly disappeared, while the frequency of penicillin-resistance has increased. Today both the phage-type pattern and antibiotic resistance are nearly similar for strains from hospital-acquired and community-acquired cases. In hospitals the frequency of bacteremia after postoperative wound infections has decreased, while cases associated with intravascular catheters has increased, and these infections are now the most common cause of hospital-acquired S. aureus bacteremia. Endocarditis is most commonly found in community-acquired cases without an identified primary focus in patients between 21-50 years. Also hematogenous osteomyelitis is most common in community-acquired cases, but these infections have changed to having a high predilection for the vertebral column, and the prevalence of chronic cases has decreased.

The in vitro activity of deferoxamine (DFO) both per se and in combination with the reductant ascorbic acid (AA) was determined against 10 E. coli strains, 5 P. mirabilis strains, and 10 coagulase-negative staphylococci. In terms of interaction, the influence of DFO on the activities of cephalothin and gentamicin was furthermore investigated against the same panel of strains employing a macrobroth dilution technique and killing-curve kinetics. The MICs of cephalothin and gentamicin were lowered for one half of the strains. Moreover, DFO prolonged the generation times of logarithmic growth phase considerably, especially when the reductant AA was present. The interactions between DFO or DFO+AA and subinhibitory concentrations of antibiotics were established by the application of growth constants, and resulted in synergy for 15 out of 25 strains with cephalothin and 9 out of 25 strains with gentamicin.

Among 3394 patients with Staphylococcus aureus bacteraemia from the years 1986–1989, 88 patients were found whose intravenous catheter and blood grew organisms of the same phage type. Strains of phage type 95 were more frequent among the patients with confirmed catheter-related bacteraemia than among other bacteraemia cases. Strains with particular phage-type patterns occurring with increasing frequency in Denmark during recent years also occurred with significantly higher frequencies among the confirmed catheter-related bacteraemias. No major differences in antibiotic resistance were observed. Patients with catheter-related bacteraemia had, in spite of a higher frequency of underlying diseases, a lower mortality compared with other bacteraemia patients, and endocarditis occurred less frequently (2% vs . 6%). Among 201 S. aureus isolates from catheters in 1988 only strains of group I occurred with increased frequency. The possible role of catheters as selection pressure on the S. aureus population is discussed.

The purpose of this study was to assess the accuracy of test strips for urinary nitrite and leucocytes for detection of bacteriuria in elderly patients. The material consisted of 213 urine samples from 85 women and 26 men (median age 79 years, range 60-93 years) within the first two days in hospital. The results of the test strip reactions were read in the department and in the laboratory. The strip test results and symptoms of UTI were compared with culture results. 27% of the samples showed significant bacteriuria on culture (or = 10(5) colonies/ml urine). 21% of the 102 patients who had submitted two urine samples within the first two days had significant bacteriuria in both samples. Less than half of these patients had symptoms of UTI. The false negative rate of test strips (defined as the number of proven laboratory UTIs not demonstrated by the test strips, expressed as a percentage of the total number of proven UTIs) was 29% in the department and in the laboratory it was 13%. 15% of the test strips at the laboratory failed to detect significant E. coli infections which were predominant. In conclusion, we found that it is advisable to perform urine culture if symptoms of urinary tract infections are present.

The most important postoperative infections in general pulmonary surgery are empyema, pneumonia and wound infection. Risk factors are underlying malignant disease and the duration of the operation. The extent of pulmonary resection also appears to be of a certain significance. Five prospective randomized, double-blind, placebo-controlled investigations are available. Together, these investigations demonstrate that prophylactic antibiotic treatment, in which the first dose is administered immediately prior to operation, reduces the frequency of pneumonia (from 27% to 17%) and the frequency of wound infection (from 18% to 4%). Despite antibiotic prophylaxis, empyema occurs with frequency of 3%. Prophylactic antibiotic treatment has also reduced the duration of hospitalization and the postoperative employment of antibiotics. The relatively few comparative investigations have not indicated unanimously that any particular antibiotic was more advantageous than other. At present, we have insufficient knowledge about the pathogenesis of the above mentioned postoperative infections. Such knowledge could increase the possibility of other prophylatic measures.

Of the 15,170 cases of bacteremia due to Staphylococcus aureus that occurred in Denmark between 1959 and 1988, we review 525 cases of acute hematogenous osteomyelitis and 185 cases of septic arthritis that developed subsequent to the bacteremia and 134 cases of contiguous osteomyelitis in which the bacteremia developed secondarily. The pattern of acute infections of bones and joints has changed over the three decades studied. The frequency of secondary bone or joint infections due to S. aureus bacteremia has changed, as have the phage-type pattern and antibiotic resistance of the infective strains. The prevalence of hospital-acquired cases has increased and the age distribution of patients has changed, as is reflected in an increasing number of older patients. The localization of hematogenous osteomyelitis has shifted, and the vertebral column is now the most common site of infection. The rate of chronic cases of osteomyelitis that occur following acute hematogenous osteomyelitis has been reduced from 34% to 6%. The mortality associated with S. aureus bacteremic infections of bones or joints is low compared to that associated with other cases of S. aureus bacteremia.

The bacteriology, epidemiology, infection types and mortality were reviewed in 407 cases of Staphylococcus aureus bacteraemia in the period 1967–1984 in children less than one year old. The number of bacteraemia cases in this age group increased in the seventies, but only 4% of the bacteraemias seemed to be due to epidemic spreading. Neonates might be at higher risk for 5. aureus bacteraemia than older children less than one year old, and nearly all infections in the neonatal period were hospital-acquired. The mortality was 24%, and did not correlate with type of infection, but in neonates it correlated with low birthweight.

A total of 157 strains of Staphylococcus aureus of different phage patterns and penicillinase production were investigated for their susceptibility to methicillin, oxacillin, cloxacillin, dicloxacillin, flucloxacillin and cephalothin by an agar dilution method. Only strains of the 52, 52A, 80, 81 complex had significantly higher IC-50 values than the rest of the strains. No correlation was found between penicillinase production and the IC-50 values. Penicillinase susceptibility divided the antibiotics into two groups: one including methicillin, oxacillin and cephalothin, and the other included dicloxacillin, cloxacillin and flucloxacillin. Nineteen strains of S. aureus which existed in both a penicillinase producing and a penicillinase non-producing form were examined for susceptibility to the six antibiotics. The difference between penicillinase positive and penicillinase negative variants was especially marked for flucloxacillin and cephalothin. Methicillin induction prior to susceptibility testing had only a minor influence on the results. Investigation of the stability of methicillin and the four isoxazolyl penicillins against penicillinase production by 37 strains of S. aureus showed methicillin to be the most stable antibiotic. This was followed by dicloxacillin, cloxacillin, flucloxacillin, and oxacillin in that order. The order of stability was identical and independent of phage pattern and quantitative penicillinase production.

The correlation between in vitro activity, pharmacokinetic properties and effect in vivo of antibiotics has so far received relatively little attention, and the optimal dosing strategy for most antibiotics is still a matter of dispute. A review on this subject is presented based on observations from an experimental pneumococcus infection model in mice. The pneumococcus is particularly suitable as pathogen in experimental infection models for antibiotic research, since it is clinically relevant, susceptible to a range of antibiotics, and naturally virulent to most laboratory animals without the need for potentiating factors. The course of pneumococcus infection in animals is discussed in detail, including the parameters for measuring antibiotic effect in vivo. In screening models the most simple and relevant parameter is survival/death of the animal, which is usually incorporated in the determination of a 50% endpoint, e.g. the ED50 (50% effective dose). Among the variety of factors of potential influence upon the ED50, the importance of the bacterial growth kinetics in vivo is emphasized. Considering the correlation of pharmacokinetic properties with effect in vivo three parameters are considered important: The peak antibiotic concentration, the area under the drug concentration curve (AUC), and the time the antibiotic concentration remains above the minimal inhibitory concentration (time greater than MIC). For the beta-lactam antibiotics evidence is accumulating that the time greater than MIC is the most important. Comparing 14 cephalosporins in the mouse-protection test with intraperitoneal inoculation of a pneumococcus type 3, the time greater than MIC calculated from the pharmacokinetic profiles of a 5 mg/mouse dose for all the 14 cephalosporins showed a high correlation with the ED50. When studying the serum antibiotic concentrations at doses similar to the ED50's for various cephalosporins and penicillins, the time greater than MIC was the parameter that varied the least. Neither the peak drug concentrations nor the AUC's showed any correlation with effect in vivo. The role of the time greater than MIC in context with other factors such as extravascular penetration of antibiotics, serum protein binding and the post-antibiotic effect is discussed. Most other experimental studies concerning dosing strategy for the beta-lactam antibiotics, including the few clinical studies available, confirm the importance of the time factor. The clinical implication for this group of antibiotics therefore is to strive for a constant, not necessarily high, concentration above the MIC.(ABSTRACT TRUNCATED AT 400 WORDS)

Netilmicin was investigated in the treatment of complicated urinary tract infection in 169 elderly male patients. It was found to be safe and effective at the dose levels of 1.0-2.5 mg/kg, three times a day, or 2 mg/kg twice a day, eliminating approximately 50-60% of the infections. The serum half-life of netilmicin was 2-3 hours in subjects with normal renal function but increased to 10-14 hours in subjects with severe uremia. When the dosage was adjusted according to the patient's weight and serum creatinine, some nephrotoxicity occurred, possibly due to drug accumulation. Therefore, we suggest that the dose be adjusted according to reduction in creatinine clearance and when possible, monitoring serum concentrations during treatment.

A prospective investigation was undertaken to compare quantitative culture of 739 samples of urine in a microbiological laboratory with the screening methods: phase contrast microscopy examination, test strip examinations for nitrite and leukocyte esterase (Multistix-2, Ames) and "Autotrak" (automatic quantitating of the bacterial content in fluids: BBT instruments). The three screening methods were, by and large, of equal value as regards true positive diagnostic frequency (0.48-0.55) and true negative diagnostic frequency (0.92). The methods were also equally rapid but microscopy examination was by far the cheapest (0.15 Danish crowns per test as compared with 1.75 for test strips and 3.10 for "Autotrak"). In addition, microscopic examination has the further advantage, although this of lesser value where cocci are concerned, of being capable of differentiating the morphology of the bacteria and their motility. It is noted that test strips have a false negative rate of approximately 13%.