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The incidence of asymptomatic bacteriuria (ABU) increases with age and is most common for persons 80 years of age and above and in elderly living in nursing homes. The distinction between ABU and urinary tract infection (UTI) is often difficult, especially in individuals, who are unable to communicate their symptoms, and there is a lack of objective methods to distinguish between the two entities. This can lead to overuse of antibiotics, which results in the selection and dissemination of antibiotic resistant isolates. Materials and methods: From voided midstream urine samples of 211 participants ≥60 years old from nursing homes, an activity center and a general practitioners clinic, we collected 19 ABU, 16 UTI and 22 control urine samples and compared them with respect to levels of complement component C3 in urine as determined by an ELISA assay relative to creatinine levels in the same urine samples, as measured by a creatinine assay. Further, we studied all Escherichia coli isolates for selected virulence genes by multiplex PCR, and by whole-genome sequencing (WGS) for genotypes and phylogenetic clustering. Antibiotic susceptibility was determined by microtiter broth dilution. Results: We identified a prevalence of ABU of 18.9% in nursing home residents, whereas ABU was only found in 4% of elderly living in the community (p &lt, 0.001). E. coli from ABU patients were significantly more antibiotic resistant than E. coli from UTIs (p = 0.01). Prevalence of classical virulence genes, detected by multiplex PCR, was similar in E. coli isolates from ABU and UTI patients. Whole-genome sequencing of the E. coli isolates showed no specific clustering of ABU isolates compared to UTI isolates. Three isolates from three different individuals from one of the nursing homes showed signs of transmission. We demonstrated a significantly increased level of C3/creatinine ratio in ABU and UTI samples compared to healthy controls, however, there was no significant difference between the ABU and UTI group with respect to C3 level, or virulence factor genes. Conclusion: ABU was significantly more prevalent in the elderly residing in nursing homes than in the elderly living at home. Antibiotic resistance was more prevalent in E. coli from nursing homes than in UTI isolates, but there was no difference in prevalence of virulence associated genes between the two groups and no phylogenetic clustering, as determined by WGS relative to the two types of E. coli bacteriuria. The similar complement C3 response in ABU and UTI patients may indicate that ABU should be reconsidered as an infection albeit without symptoms.

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.

Recurrent urinary tract infection (rUTI) remains a major problem for many women and therefore the pursuit for genomic and phenotypic traits which could define rUTI has been ongoing. The present study applied a genomic approach to investigate recurrent urinary tract infections by comparative analyses of recurrent and non-recurrent Escherichia coli isolates from general practice. From whole-genome sequencing data, phylogenetic clustering and genomic traits were studied on a collection of isolates which caused recurrent infection compared to non-recurrent isolates. In addition, genomic variation between the 1st and following infection was studied on a subset of the isolates. Evidence of limited adaptation between the recurrent infections based on single nucleotide polymorphism analyses with a range of 0–13 non-synonymous single nucleotide polymorphisms (SNPs) between the paired isolates. This included an overrepresentation of SNPs in metabolism genes. We identified several genes which were more common in rUTI isolates, including nine fimbrial genes, however, not significantly after false-discovery rate. Finally, the results show that recurrent isolates of the present dataset are not distinctive by variation in the core genome, and thus, did not cluster distinct from non-rUTI isolates in a SNP phylogeny.

Pivmecillinam (amdinocillin pivoxil) is the recommended first choice antibiotic used to treat urinary tract infections (UTIs) in Denmark. Yet, in laboratory settings the frequency of mutation to mecillinam resistance has been found to be very high. Treatment of UTI has a good clinical response, but low bacteriological cure rates. Prevalence of mecillinam resistance in Escherichia coli remains low in spite of many years of use. We describe occurrence of in vivo mecillinam resistance in a clinical isolate of extended-spectrum β-lactamase producing E. coli following pivmecillinam treatment. The only identified phenotypic differences in MEC-R compared to the original MEC-S isolate were full-length lipopolysaccharides with O-antigen (O25), mecillinam resistance, and a lower minimum inhibitory concentration for ceftazidime. Whether the serotype change and mutation in fhlA is the cause of the mecillinam resistance is unknown. Further studies are required to elucidate this possible mechanism. We continue to recommend the use of pivmecillinam as first-line treatment for UTI, yet mecillinam treatment for other foci should be investigated.

Background: Pivmecillinam has good pharmacokinetic properties for treatment of infections in the urinary tract, and the mecillinam resistance rate in Enterobacteriaceae is very low. In a European guideline pivmecillinam is recommended as a first-line drug for treatment of lower urinary tract infections. In Danish and Norwegian guidelines pivmecillinam is also recommended for acute uncomplicated pyelonephritis, although with very sparse documentation of effect.

We surveyed European medical schools regarding teaching of prudent antibiotic prescribing in the undergraduate curriculum. We performed a cross-sectional survey in 13 European countries (Belgium, Croatia, Denmark, France, Germany, Italy, Netherlands, Norway, Serbia, Slovenia, Spain, Switzerland, United Kingdom) in 2013. Proportional sampling was used, resulting in the selection of two to four medical schools per country. A standardized questionnaire based on literature review and validated by a panel of experts was sent to lecturers in infectious diseases, medical microbiology and clinical pharmacology. In-depth interviews were conducted with four lecturers. Thirty-five of 37 medical schools were included in the study. Prudent antibiotic use principles were taught in all but one medical school, but only four of 13 countries had a national programme. Interactive teaching formats were used less frequently than passive formats. The teaching was mandatory for 53% of the courses and started before clinical training in 71%. We observed wide variations in exposure of students to important principles of prudent antibiotic use among countries and within the same country. Some major principles were poorly covered (e.g. reassessment and duration of antibiotic therapy, communication skills). Whereas 77% of the respondents fully agreed that the teaching of these principles should be prioritized, lack of time, mainly due to rigid curriculum policies, was the main reported barrier to implementation. Given the study design, these are probably optimistic results. Teaching of prudent antibiotic prescribing principles should be improved. National and European programmes for development of specific learning outcomes or competencies are urgently needed. Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved

Asymptomatic human carriage of antimicrobially drug-resistant pathogens prior to infection is increasing worldwide. Further investigation into the role of this fecal reservoir is important for combatting the increasing antimicrobial resistance problems. Additionally, the damage on the intestinal microflora due to antimicrobial treatment is still not fully understood. Animal models are powerful tools to investigate bacterial colonization subsequent to antibiotic treatment. In this chapter we present a mouse-intestinal colonization model designed to investigate how antibiotics select for an ESBL-producing E. coli isolate. The model can be used to study how antibiotics with varying effect on the intestinal flora promote the establishment of the multidrug-resistant E. coli. Colonization is successfully investigated by sampling and culturing stool during the days following administration of antibiotics. Following culturing, a precise identification of the bacterial strain found in mice feces is applied to ensure that the isolate found is in fact identical to the strain used for inoculation. For this purpose random amplified of polymorphic DNA (RAPD) PCR specifically developed for E. coli is applied. This method allows us to distinguish E. coli with more than 99.95% genome similarity using a duplex PCR method.

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.

In a mouse model using intraperitoneal inoculation of Streptococcus pneumoniae type 3, the 50% effective dose, ED50, after single doses one hour post-inoculation was considerably lower for ceftriaxone (CRO) than for cefuroxime (CXM) and cefotaxime (CTX), in spite of the same minimal inhibitory concentration, MIC, of 0.02 mcg/ml against the pneumococcus for all 3 drugs. The bactericidal activity as measured by time-kill curves was similar for the 3 drugs, as was the post-antibiotic effect in vitro. Protein binding in mouse serum was considerably higher for CRO (87%) than for both CTX (35%) and CXM (15%), respectively. Of pharmacokinetic parameters investigated on doses equal to the ED50s, the time the serum antibiotic concentration remained above the MIC (delta T(MIC)) was the factor that varied the least among 3 drugs. Therefore, the superior in vivo effect for CRO is not due to higher intrinsic activity against the pathogen but to the long serum-elimination half-life resulting in an extended delta T(MIC), probably related to the high serum protein binding.

Fluoroquinolones are among the drugs most extensively used for the treatment of bacterial infections in human and veterinary medicine. Resistance to quinolones can be chromosome or plasmid mediated. The chromosomal mechanism of resistance is associated with mutations in the DNA gyrase- and topoisomerase IV-encoding genes and mutations in regulatory genes affecting different efflux systems, among others. We studied the role of the acquisition of a mutation in the gyrA gene in the virulence and protein expression of uropathogenic Escherichia coli (UPEC). The HC14366M strain carrying a mutation in the gyrA gene (S83L) was found to lose the capacity to cause cystitis and pyelonephritis mainly due to a decrease in the expression of the fimA , papA , papB , and ompA genes. The levels of expression of the fimA , papB , and ompA genes were recovered on complementing the strain with a plasmid containing the gyrA wild-type gene. However, only a slight recovery was observed in the colonization of the bladder in the GyrA complement strain compared to the mutant strain in a murine model of ascending urinary tract infection. In conclusion, a mutation in the gyrA gene of uropathogenic E. coli reduced the virulence of the bacteria, likely in association with the effect of DNA supercoiling on the expression of several virulence factors and proteins, thereby decreasing their capacity to cause cystitis and pyelonephritis.

Modern urine-meters are provided with the urine collection bag directly attached to the measuring device, thus providing a closed collection system. The systems vary, however, in respect to how the measuring devices are emptied into the urine collection bag. Using an in vitro ascending contamination model we compared three systems: the Unometer (Unomedical), the Bard Urinemeter and the Curity Urinemeter (Kendall), which all differ in the methods of emptying. The urine collection bags were inoculated with Pseudomonas aeruginosa , and subsequently sampled daily at six different sites for up to seven days in order to determine the degree and timing of ascending contamination of the systems. Unometer was significantly less contaminated at the urine-meter level at day seven than both Bard (0/8 vs. 4/4, P=0.002) and Curity (0/8 vs. 8/8, P=0.0002), respectively, as well as significantly less contaminated in the infusion-catheter above the urine-meter at day seven than Bard (0/8 vs. 4/4, P= 0.002), but not so as compared to Curity (0/8 vs. 1/8, P =1,0). The Bard and Curity systems empty the devices by tilting thereby probably contaminating the devices, while the Unometer is emptied via a non-return valve in the bottom of the device.

Objective 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. Patients and methods 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. Results 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 andin 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 ≈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). Conclusion 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 correlation between pharmacokinetic parameters and the in-vivo effect of antibiotics in relation to bacterial growth phases was evaluated using the mouse peritonitis model with a penicillin-resistant pneumococcus. Different 8 h dosing regimens were applied, with different total doses and initiated at different times during the bacterial growth phase. The effect was measured as the decline in bacterial counts in the peritoneal cavity. The pharmacokinetic parameters showed major changes during the phases of growth, as the serum elimination of penicillin decreased during the infection. The same effect of dosing regimens was observed in the exponential and stationary phases. In two regimens where T(>MIC) (the time the serum concentration exceeded the MIC) was 50% of the treatment period, a significantly better effect was achieved with a 2 hourly regimen than with a regimen with treatments every 20 min. The T(>MIC) of each dose was shown to be a critical parameter for achieving an effect in all growth phases. The maximum effect of penicillin, a 5-6 x log10 decline in bacterial counts in the peritoneum of the mice, was achieved when T(>MIC) was >50% of the treatment time or longer than approximately 40 min of each dose. The 50% effective dose for protection after a single injection, ED50, was measured in the different phases of the infection and found to increase with the duration of the pneumococcal infection, while mice treated 24 h after challenge were beyond therapeutic range. The correlation between the effect of penicillin and pharmacokinetic parameters appears to follow the same rules during the different in-vivo growth phases of pneumococci.

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 Danish Integrated Antimicrobial Resistance Monitoring and Research Programme (DANMAP) has published its annual report

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.

Sixty-two aminoglycoside-resistant Gram-negative enteric bacteria were isolated over a 3-year period from two hospitals (Bispebjerg and Esbjerg) among a total of almost 270,000 isolates. These hospitals were selected because of their different aminoglycoside policies during the years investigated. At Bispebjerg Hospital the principal aminoglycoside used was tobramycin, while gentamicin was the first choice at Esbjerg Hospital. Escherichia coli was the most frequently found aminoglycoside-resistant species. Among the 61 aminoglycoside-resistant strains studied, resistance was due to aminoglycoside-modifying enzymes in all except two Xanthomonas maltophilia strains. The ANT(2") enzyme occurred significantly more often at Esbjerg Hospital (p = 0.001), while enzymes of the AAC(3) or AAC(6') moieties were more common, but not significantly so, at Bispebjerg Hospital. The phenotypic pattern of aminoglycoside resistance, as determined by disc diffusion, correlated 100% with the ANT(2") and AAC(3)-V (the two most common enzymes among the isolates) genotype of the organisms as established using DNA probes. Median minimum inhibitory concentrations (MICs) (mg/l) for clinically utilized aminoglycosides were: amikacin (1.6), gentamicin (25.0), kanamycin (50.0), netilmicin (1.6-25.0) and tobramycin (12.5-50.0). Isolates from Bispebjerg Hospital revealed significantly higher MICs for netilmicin and tobramycin (p0.01) as compared to isolates from Esbjerg Hospital.

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.

A collection of 99 clinical isolates of Streptococcus pneumoniae, chosen due to their different susceptibilities to penicillin, were investigated with respect to their susceptibility to the macrolides azithromycin, clarithromycin, dirithromycin, erythromycin, roxithromycin, spiramycin, and to clindamycin and tetracycline by the agar dilution method. We found complete cross resistance among the macrolides. The pneumococci were either susceptible, MICor = 0.5 micrograms/ml, or resistant, MICor = 16 micrograms/ml, to the tested macrolides, giving a bimodal distribution. In addition, complete cross resistance was observed between clindamycin and macrolides. Pneumococci resistant to macrolides were also resistant to tetracycline, and 26% of the macrolide-susceptible strains were tetracycline resistant.

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.

The in vitro activity of deferoxamine (DFO) combined with cephalothin, gentamicin, cefotaxime, vancomycin, and fusidic acid, in the presence or absence of the reductant ascorbic acid (AA) was investigated against Staphylococcus aureus by a macrobroth dilution technique and killing curve kinetics. DFO and in particular DFO + AA lowered the MICs of cephalothin, gentamicin, cefotaxime, and fusidic acid for most of the strains and in some instances also the MICs of vancomycin. To characterize the interaction between DFO or DFO + AA and antimicrobials we applied the growth constants of logarithmic growth phase. Generally DFO acted synergistically with cephalothin, gentamicin, vancomycin, and fusidic acid, particularly in the presence of AA, and in some cases synergy was demonstrated with cefotaxime, too.

A total of 49 gentamicin-resistant strains of Staphylococcus aureus isolated from blood (n = 26) or from other sites (n = 23) during the years 1979 to 1987 were evaluated for the presence of aminoglycoside-inactivating enzymes on the basis of minimum inhibitory concentrations measured by agar dilution as well as inhibition zone diameters determined by disc diffusion. Enzymatic activity was caused by AAC (6')III/APH (2") in 45 strains, and by AAC (6')III/APH (2") + APH (3') in four strains. No changes in the distribution of enzymatic activity were observed during the eight years.

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.