Cost-effectiveness analysis of Chlamydia trachomatis screening in Dutch pregnant women.

Chlamydia trachomatis infections during pregnancy may have serious consequences for women and their offspring. Chlamydial infections are largely asymptomatic. Hence, prevention is based on screening. The objective of this study was to estimate the cost-effectiveness of C. trachomatis screening during pregnancy. We used a health-economic decision analysis model, which included potential health outcomes of C. trachomatis infection for women, partners and infants, and premature delivery. We estimated the cost-effectiveness from a societal perspective using recent prevalence data from a population-based prospective cohort study among pregnant women in the Netherlands. We calculated the averted costs by linking health outcomes with health care costs and productivity losses. Cost-effectiveness was expressed as net costs per major outcome prevented and was estimated in base-case analysis, sensitivity, and scenario analysis. In the base-case analysis, the costs to detect 1000 pregnant women with C. trachomatis were estimated at €527,900. Prevention of adverse health outcomes averted €626,800 in medical costs, resulting in net cost savings. Sensitivity analysis showed that net cost savings remained with test costs up to €22 (test price €19) for a broad range of variation in underlying assumptions. Scenario analysis showed even more cost savings with targeted screening for women less than 30 years of age or with first pregnancies only. Antenatal screening for C. trachomatis is a cost-saving intervention when testing all pregnant women in the Netherlands. Savings increase even further when testing women younger than 30 years of age or with pregnancies only.

Chlamydia trachomatis respiratory infection in Dutch infants.

Chlamydia trachomatis is the most common bacterial pathogen causing sexually transmitted infections in Dutch adults. As prenatal screening for C trachomatis and treatment of pregnant women is not routine practice in The Netherlands, perinatal transmission of C trachomatis may therefore occur. The presence of C trachomatis in infants less than 6 months of age who presented with respiratory complaints to the Erasmus MC-Sophia hospital was evaluated. Respiratory specimens, primarily nasopharyngeal swabs, were tested for C trachomatis, respiratory viruses and Mycoplasma pneumoniae using PCR, viral isolation in cell cultures and direct immunofluorescence. C trachomatis respiratory tract infection was confirmed to be relatively common with detection in 10 of 148 (7%) infants tested. C trachomatis had not been tested for by the attending physicians, but was the second most frequently detected respiratory pathogen after human Respiratory Syncitial Virus, which was found in 41 (28%) infants.

Use of pooled urine samples and automated DNA isolation to achieve improved sensitivity and cost-effectiveness of large-scale testing for Chlamydia trachomatis in pregnant women.

The success of large-scale screening for Chlamydia trachomatis depends on the availability of noninvasive samples, low costs, and high-quality testing. To evaluate C. trachomatis testing with pregnant women, first-void urine specimens from 750 consecutive asymptomatic pregnant women from the Rotterdam area (The Netherlands) were collected. Initially, we investigated the performance of three different DNA isolation methods with 350 of these urines and 70 pools of 5 of the same subset of urine samples. The routinely used COBAS AMPLICOR test was compared to the COBAS AMPLICOR test with prior DNA isolation by use of the MagNA Pure large-volume kit and the MagNA Pure bacterial DNA isolation kit. The latter combination provided the best DNA test for pooled urines, with a sensitivity twice that of the other methods. Next, using all 750 urines, the COBAS AMPLICOR performance for individual testing was compared to pooled testing with the standard COBAS AMPLICOR procedure and subsequently to pooled testing with COBAS AMPLICOR in combination with the MagNA Pure bacterial DNA isolation kit. The sensitivity of COBAS AMPLICOR was 65% on individual and 42% on pooled urines but improved to 92% on pooled urines with the MagNA Pure bacterial DNA isolation kit, making this combination the best screening method. The C. trachomatis prevalence in this population appeared to be 6.4%. Additionally, the cost of the combined MagNA Pure bacterial DNA isolation kit and COBAS AMPLICOR method on pooled urines was only 56% of the cost of the standard COBAS AMPLICOR test applied to individual urines. Costs per positive case detected in the combined method were 39% of standard costs.

Prevalence of STD and HIV infections among attenders of the Erasmus MC STD clinic, Rotterdam, The Netherlands, during the years 1996 to 2000.

The purpose of the study was to investigate possible changes in the prevalence of STD and HIV collected at a Dutch STD clinic in the period 1996 to 2000. Age, gender, ethnic background, sexual preference, intravenous drug use and STD or HIV infection in persons attending an STD outpatient clinic were analysed and compared. The prevalence of HIV infection among the clinic visitors remained stable. The prevalence of Neisseria gonorrhoeae and Chlamydia trachomatis infections increased significantly among heterosexual men and heterosexual women. Among homo- and bisexual men a significant increase was seen in chlamydial infections only. Because of the increasing prevalence of gonococcal and chlamydial infections among STD clinic visitors in Rotterdam, more attention should be paid to coordinated preventive activities, such as health education and contact tracing. Further subgroup analyses should be done in order to get more information on risk behaviour in the different groups.

Sensitivity and specificity of three new commercially available Chlamydia trachomatis tests.

In order to determine the value of new Chlamydia trachomatis (Ct) specific tests for routine serological diagnosis of Ct infections, we evaluated several commercially available assays (C. trachomatis enzyme immunoassay (EIA), Labsystems (CtL); SeroCT, Savyon (CtS); pELISA, Medac (CtMp)) in various study populations. The prevalence of C. trachomatis-specific IgA antibodies in a blood donor population (n = 443) as determined by the peptide based tests CtL, the CtS and the CtMp was 5%, while for IgG antibodies this was 6% (CtL and CtS) and 12% (CtMp) respectively. Prevalence was negatively correlated with age, concording with C. trachomatis specificity. None of the three tests showed significant titre rises in serum samples taken from patients with a proven infection of Chlamydia pneumoniae (n = 22), indicating species-specificity for all three tests. In patients with a polymerase chain reaction proven (n = 324) Ct infection, 75%, 70% and 68% were positive for IgG and 45%, 38% and 47%, positive for IgA as determined by the CtMp, CtL and CtS respectively. We conclude that the new synthetic peptide-based EIA tests are able to detect species-specific Ct antibodies, which are strongly correlated to (active) infection.

Tubal factor pathology caused by Chlamydia trachomatis: the role of serology.

One of the causes of infertility in females is tubal pathology as a result of pelvic inflammatory disease (PID) caused by Chlamydia trachomatis (Ct). Diagnosis and identification of patients is hampered by the lack of rapid, easy, sensitive and specific methods. The introduction of Ct-specific enzyme-linked immunosorbent assay (ELISA) tests, based upon synthetic peptides may subsequently increase the sensitivity and specificity for the detection of tubal factor infertility caused by Ct. In order to determine the value of these tests for serological diagnosis of Ct infections, we evaluated several commercially available assays (C. trachomatis enzyme immunoassay (EIA), Labsystems (CtL); SeroCT, Savyon (CtS); pELISA, Medac (CtMp); and a reference assay rELISA, Medac (CtMr)) in two study populations. The first group consisted of 134 female patients with infertility problems. Tubal factor infertility was observed in 85 of these patients (63%). A higher % positivity was found for Ct-specific IgG for the CtL, CtS and CtMp, 41% vs 10%, 57% vs 18% and 55% vs 25% respectively as compared to patients with infertility due to other problems. A similar trend was observed for Ct-specific IgA. The specificity of Ct-specific IgA and IgG in this patient group varied between 92 to 98% and 76 to 90%, respectively. The second group consisted of 107 consecutive gynaecology patients with fertility problems or suspected PID. In this particular patient group, the specificity of the peptide based tests were around 80% and 90% for Ct-specific IgA and 75% and 85% for Ct-specific IgG, respectively. The negative predictive values exceeded 90%, while the positive predictive values varied from 30% to 47% for Ct-specific IgA and was around 30% for Ct-specific IgG. Testing Ct-specific IgG had no additional value above Ct-specific IgA alone. We conclude that the new synthetic peptide-based EIA tests are able to detect species-specific antibodies, which are correlated to (active) infection, and that in particular IgA may be useful in the serodiagnosis of tubal factor infertility caused by C. trachomatis, and will contribute in simplifying the work-up in patients with infertility.

Molecular detection of Mycoplasma pneumoniae in adults with community-acquired pneumonia requiring hospitalization.

Mycoplasma pneumoniae infection was diagnosed in 18 (12.5%) of 144 adults hospitalized with community-acquired pneumonia. The infection was demonstrated by PCR in 15 patients and by serology, using two methods, in 10 patients. The mean age of the 8 patients with positive M. pneumoniae PCR and negative serology was significantly higher than that of the 10 patients with positive serology.

Impact of hospital-wide surveillance on hospital-acquired infections in an acute-care hospital in the Netherlands.

The goal of surveillance is to identify hospital-acquired infections (HAI) and risk factors, to apply targeted interventions and to evaluate their effect in an ongoing system. Continuing active surveillance in a 270-bed acute-care hospital is being performed on clinical patients, excluding day-care. The period 1984-1997 is described here. Specific surveillance-based interventions included the introduction of antimicrobial prophylaxis in gynaecology patients with postoperative urinary tract catheters and inpatients scheduled for appendicectomy and hysterectomy. General measures included education, implementation of protocols, feedback of surgeon-specific infection rates. In total, 3545 HAI were found in 13 years of surveillance. The incidence was 4.7/100 admissions and 4. 5/1000 patient days. Age-specific incidences ranged from 1.3 in the age-category 1-14 years, to 10.2 in patients aged 75 years and above. If age-specific incidences had remained at their 1984 level, over 3000 additional infections would have occurred, affecting all age groups except those up to 14 years. The distribution of types of infections differed between services. Following the targeted interventions, the rate of infections in gynaecology decreased from 19.4 per 1000 patient days in 1984 to 2.4 per 1000 patient days in 1996. The rates of wound infection following appendicectomy and hysterectomy decreased by 69% and 82%, respectively, in the period following the institution of antimicrobial prophylaxis. Over 4000 micro-organisms were isolated from the HAI; multi-resistant strains were isolated sporadically. We conclude that hospital-wide surveillance of hospital-acquired infections provides appropriate targets for interventions tailored to the specific needs of the hospital. The impact of such interventions can readily be documented from the surveillance data.

[Prevalence of sexually transmitted diseases (STD) and HIV-infection among attendees of STD Outpatient Clinic, Dijkzigt University Hospital in Rotterdam; comparative analysis of years 1993 and 1998]. / Prevalentie van seksueel overdraagbare aandoeningen (SOA) en HIV-infectie bij bezoekers van de SOA-polikliniek van het Academisch Ziekenhuis Rotterdam-Dijkzigt; een vergelijking van de jaren 1993 en 1998.

OBJECTIVE: To gain an impression as to the possible trends in the prevalence of VD and HIV between 1993 and 1998. DESIGN: Retrospective. METHOD: Data of age, gender, ethnic background, sexual preference, intravenous drug use and a diagnosis of VD or HIV infection for persons attending the VD Outpatient Clinic of the Department of Dermato-Venereology of the Dijkzigt University Hospital in Rotterdam, the Netherlands, for the first time were compared for the years 1993 and 1998. RESULTS: The number of patients examined was 3099 (1894 men and 1205 women) in 1993 and 3696 (1878 men and 1818 women) in 1998. No diagnosis of venereal disease was made in 58.9% and 56.2% of them, respectively. The prevalence of HIV infection decreased from 1.3% in 1993 to 0.6% in 1998. This was caused mainly by a decline in the prevalence of HIV-antibodies among men with homosexual contacts. In the total population, the prevalence of Neisseria gonorrhoeae and Chlamydia trachomatis decreased significantly (from 5.4% to 2.5% and from 9.3% to 7.5%, respectively), but there was no similar decrease among the men with homosexual contacts.

Chlamydial and gonococcal infections in Curacao: prevalence and determinants

OBJECTIVE: To determine prevalence and determinants of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections among asymptomatic women and men in Curacao. DESIGN AND METHODS: This was a cross-sectional population-based study. Urine samples (n=579) were collected from Antillean people, > 18 years, randomly selected from participants of a 1994 population survey (the Curacao Health Study, n=2,248). For the detection of CT and Erasmus Medical Center, Rotterdam. RESULTS: CT and NG infections were found in 6.1 percent and 1.0 percent of samples, respectively. Concomitant CT and NG infection did not occur. Most CT infections were found in persons <44 years of age, the highest prevalence was found in the 18-24 year age group, 17.4 percent (13/75). In contrast, most NG infections were found in persons >44 years. CT infection, but not NG infection, was correlated with indices of low socio-economic status. Multiple regression confirmed the association of CT infection with age and socio-economic class. CONCLUSION: In Curacao, CT and NG infections are not epidemiologically linked. CT infection is highly prevalent and calls for a screening-intervention model based on prevalence and risk factors. (Au)

Evaluation of PCR, culture, and serology for diagnosis of Chlamydia pneumoniae respiratory infections.

We prospectively studied 156 patients with a diagnosis of community-acquired pneumonia requiring admission. Several respiratory specimens were obtained for the detection of Chlamydia pneumoniae by cell culture and PCR. Three serum samples were obtained from each patient. Serological diagnosis of a C. pneumoniae infection was determined by the microimmunofluorescence (MIF) test, the complement fixation (CF) test, and recombinant lipopolysaccharide (LPS) enzyme-linked immunosorbent assay (ELISA; referred to as the rDNA LPS ELISA). Twenty-three patients (15%) had serological results compatible with acute C. pneumoniae infection; nine (39%) of these subjects were C. pneumoniae PCR positive. Twenty-two patients (14%) had positive PCR results without serological evidence of an acute C. pneumoniae infection. An attempt was made to calculate the sensitivities and specificities of the MIF test, rDNA LPS ELISA, and PCR for the diagnosis of chlamydial community-acquired pneumonia. Several "gold standards" were defined. Generally, the sensitivities of the rDNA LPS ELISA and MIF were comparable, while the sensitivity of the CF test was shown to be very low. Independent of the gold standard used, the best PCR results were obtained with nasopharyngeal specimens. However, the predictive value of a positive C. pneumoniae PCR result for patients with community-acquired pneumonia remains unknown and may be low. Although a widely accepted gold standard is still lacking, the rDNA LPS ELISA may currently be the preferred tool for diagnosing acute respiratory Chlamydia infections in routine clinical practice. However, the MIF test remains the method of choice for determining the prevalence of C. pneumoniae infections in a given community.

Diagnosis of Chlamydia pneumoniae infection in patients with chronic obstructive pulmonary disease by micro-immunofluorescence and ELISA.

The incidence of Chlamydia pneumoniae infection was determined in patients with chronic obstructive pulmonary diseases (COPD) by prospective serial serology. Chlamydia-specific IgG, IgM and IgA antibodies were detected with a recombinant DNA lipopolysaccharide (LPS) ELISA as well as with a micro-immunofluorescence (MIF) assay with C. pneumoniae elementary bodies. From 271 consecutive COPD patients who visited the outpatient clinic of the department of pulmonary diseases (211 males, 60 females, age range 34-88 years, mean age 66 SD 10 years), blood samples (n = 1058) were taken every 2-7 months; the observation period ranged from 3 to 19 months (mean 15 SD 4). The prevalence of chlamydial IgG was 72% with the MIF and 53% with the rDNA LPS ELISA. More than 90% of the COPD patients had no significant changes in their chlamydia-specific IgG, IgA and IgM titres in either test during the observation period. Seven (3%) patients had MIF results indicating acute C. pneumoniae infection during their surveillance period, of whom five were confirmed by rDNA LPS ELISA. Eleven (4%) additional patients were infected during observation, as determined by rDNA LPS ELISA only. These patients had significantly elevated C. pneumoniae-specific IgG and IgA MIF titres, as compared with the patients without infection. All 18 patients with serological evidence of acute infection during their surveillance period were re-tested in a commercial MIF test that can distinguish between C. pneumoniae, C. trachomatis and C. psittaci LPS-specific antibodies, but no evidence of C. trachomatis or C. psittaci infection was found. The incidence of chlamydial infection was 2.2 and 5.3/100 person-years, when diagnosed by MIF and rDNA LPS ELISA, respectively. It is concluded that the rDNA LPS chlamydia assay may currently be the most sensitive serological tool for diagnosing recent respiratory chlamydia infections and that C. pneumoniae infection occurs frequently in COPD patients.

Comparison of three commercially available amplification assays, AMP CT, LCx, and COBAS AMPLICOR, for detection of Chlamydia trachomatis in first-void urine.

We compared the Gen-Probe transcription-mediated amplification assay (AMP CT), the Abbott LCx assay, and the Roche COBAS AMPLICOR assay for the detection of Chlamydia trachomatis in a mixed population in urine samples. First-void urine, urethral specimens, and cervical specimens in females were obtained from 1,000 patients (544 males and 456 females) visiting the outpatient sexually transmitted disease clinic of our hospital. The prevalence of C. trachomatis infection was 7.7% as determined by tissue culture of urethral and cervical specimens. The sensitivities of LCx, COBAS AMPLICOR, and AMP CT compared to cell culture were 79, 86, and 78%, respectively. Sensitivity and specificity were recalculated by using a new "gold standard", i.e., a sample was considered to be true positive if two or more techniques yielded positive results. Specimens positive only by cell culture or positive in only one commercial amplification technique were retested by a previously described in-house PCR. After discordance analysis the sensitivities of LCx, COBAS AMPLICOR, and AMP CT were 84, 93, and 85%, respectively. Specificity exceeded 99% for all three assays. With each method the sensitivity was lower for urine samples from females compared to urine samples from males. By application of this new gold standard, existing differences between methods are highlighted; future evaluations of new techniques should be validated against two or more amplification assays.

Widely used, commercially available Chlamydia pneumoniae antigen contaminated with mycoplasma.

Mycoplasma contamination was detected in a widely used commercially available Chlamydia pneumoniae antigen preparation. Contamination was studied with a mycoplasma group-specific 16S rRNA polymerase chain reaction (PCR) and sequence analysis. Several lots of the purified C. pneumoniae antigen from the Washington Research Foundation appeared to be contaminated with the same Mycoplasma species, which appeared to be closely related to M. arginini. Antigen slides prepared for the detection of chlamydia antibodies by MRL Diagnostics were contaminated with the same Mycoplasma sp. Chlamydia antigen slides from Labsystems OY and two chlamydia complement fixation reagents (Virion International Distribution Ltd and Behring Werke) were not contaminated. It is concluded that commercially available C. pneumoniae antigens may contain mycoplasma antigens as well. Although the impact of such mycoplasma contamination on the results of chlamydia serology may not be significant, routine screening of all antigen preparations obtained by tissue culture before their distribution and use is recommended.

Detection of PCR inhibitors in cervical specimens by using the AMPLICOR Chlamydia trachomatis assay.

To determine that susceptibility of AMPLICOR Chlamydia trachomatis PCR to inhibitory factors possibly present in cervical specimens, we obtained cervical specimens from 200 gynecology patients attending our outpatient clinic. The prevalence of C. trachomatis infection was 4.1%, as determined by cell culture. All AMPLICOR specimens were tested in one procedure as described by the manufacturer, and after the specimen was spiked with C. trachomatis, several other pretreatment protocols were used. Complete inhibition of the PCR was observed in 38 (19%) cervical specimens. Heat treatment at 95 degrees C, freeze-thawing, or 10-fold dilution of the samples reduced the initial inhibition to 9, 16, or 9%, respectively. A combination of heat treatment and 10-fold dilution reduced the inhibition to 4% of the samples. A second specimen type (swabs inoculated in 0.2 M sucrose phosphate buffer [2SP]) was also evaluated. A 10-fold dilution of the spiked 2SP specimen resulted in an inhibition rate of 6%, which was comparable to that obtained by centrifugation of the 2SP specimen prior to processing. Furthermore, it was shown that the inhibition was not correlated with blood contamination. Processing the specimens on the day of collection or the day after resulted in a higher inhibition rate than did delayed processing (27.6 versus 15.5%, respectively). An inverse correlation was found between the concentration of C. trachomatis added to the sample and the rate of inhibition observed. The inhibition was partly correlated with the pH of the cervical mucosa. Decreased inhibition was found at pH values of > or = 7.5. The effects of blood, pH, and delay in processing were all evaluated by using the AMPLICOR specimen. We conclude that the susceptibility of AMPLICOR C. trachomatis PCR to inhibiting factors in cervical specimens can be significantly reduced if the pretreatment procedure includes heat treatment or the use of 2SP transport medium. Also, a 10-fold dilution of the clinical specimen followed by heat treatment will largely prevent the inhibition of this PCR.

Mesothelial cell adherence to vascular prostheses and their subsequent growth in vitro.

Cell seeding may decrease the thrombogenicity of implanted vascular grafts, but its application is hampered by the limited availability of autologous endothelial cells. Human peritoneal mesothelial cells have blood flow supporting qualities and are readily available. This study investigated the adherence of mesothelial cells to vascular prostheses and their subsequent growth in vitro. Circular pieces of various vascular prosthetic materials were seeded with 51Chromium-labeled mesothelial and endothelial cells and left for either 5, 15, 30, 60, and 120 minutes. The unattached cells were removed and the degree of cell attachment was measured. The number of mesothelial cells to Dacron increased during the first 60 min up to 35.2% of the seeded inoculum whereafter a plateau was reached. Scanning electron microscopy showed spread mesothelial cells adherent to the Dacron fibers. A significant increase in adherence was observed after preincubation of Dacron with 10 micrograms/mL fibronectin, but no improvement was found after preincubation with human serum albumin or gelatin. Mesothelial cells adhered better to Gel-coated than to Gel-sealed or plain Dacron. The adherence of mesothelial cells to ePTFE (Teflon) was significantly poorer. No significant differences in adherence were found between mesothelial and endothelial cells. Mesothelial cell growth on Dacron resulted in a modest increase in the number of viable cells during 27 days, which implies biocompatibility of Dacron and mesothelial cells in vitro.

Age-related interference with Chlamydia pneumoniae microimmunofluorescence serology due to circulating rheumatoid factor.

Microimmunofluorescence (MIF) serology is commonly used in the diagnosis of chlamydial infections. In the MIF assay, Chlamydia pneumoniae elementary bodies were used to detect C. pneumoniae immunoglobulin G (IgG) and IgM antibodies in paired serum samples from 286 patients with respiratory illnesses. In 69 patients, MIF serology was compared with C. pneumoniae cultures. All C. pneumoniae cultures remained negative. However, 205 (71%) of 286 patients were C. pneumoniae antibody positive and 64 (22%) had MIF test results indicating recent infection; 11 showed a fourfold increase in IgG titer, 18 had IgG titers of greater than or equal to 1:512, and 41 had IgM titers of greater than or equal to 1:16. In 35 (55%) of 64 patients, a recent-infection diagnosis was based on C. pneumoniae IgM antibodies only. However, 78% of C. pneumoniae IgM-positive patients had circulating rheumatoid factor (RF) by rheumatoid arthritis latex assay. RF positivity increased with age. After absorption with anti-human IgG, all C. pneumoniae IgM-positive sera became C. pneumoniae IgM negative in the MIF assay. Twenty-five patients with active rheumatoid arthritis but without respiratory illness were also tested; 14 were C. pneumoniae IgG positive and C. pneumoniae IgM positive as well. Absorption of IgG from these RF-containing sera invariably resulted in disappearance of reactivity in the MIF IgM assay. We conclude that with age the serologic diagnosis of recent C. pneumoniae infection becomes increasingly prone to false-positive results unless sera are routinely absorbed prior to MIF IgM testing.

Prophylactic ciprofloxacin for catheter-associated urinary-tract infection.

Patients receiving antibiotics during bladder drainage have a lower incidence of urinary-tract infections compared with similar patients not on antibiotics. However, antibiotic prophylaxis in patients with a urinary catheter is opposed because of the fear of inducing resistant bacterial strains. We have done a double-blind, placebo-controlled trial of prophylactic ciprofloxacin in selected groups of surgical patients who had postoperative bladder drainage scheduled to last for 3 to 14 days. Patients were randomly assigned to receive placebo (n = 61), 250 mg ciprofloxacin per day (n = 59), or 500 mg ciprofloxacin twice daily (n = 64) from postoperative day 2 until catheter removal. 75% of placebo patients were bacteriuric at catheter removal compared with 16% of ciprofloxacin-treated patients (relative risk [RR] [95% CI] 4.7 [3.0-7.4]). The prevalence of pyuria among placebo patients increased from 11% to 42% while the catheter was in place; by contrast, the rate of pyuria was 11% or less in patients receiving ciprofloxacin (RR 4.0 [2.1-7.3]). 20% of placebo patients had symptomatic urinary-tract infections, including 3 with septicaemia, compared with 5% of the ciprofloxacin groups (RR 4.0 [1.6-10.2]). Bacteria isolated from urines of placebo patients at catheter removal were mostly species of enterobacteriaceae (37%), staphylococci (26%), and Enterococcus faecalis (20%), whereas species isolated from urines of ciprofloxacin patients were virtually all gram-positive. Ciprofloxacin-resistant mutants of normally sensitive gram-negative bacteria were not observed. Ciprofloxacin prophylaxis is effective and safe in the prevention of catheter-associated urinary tract infection and related morbidity in selected groups of patients requiring 3 to 14 days of bladder drainage.

Impact of concurrent antimicrobial therapy on catheter-associated urinary tract infection.

Results of a survey in two Dutch district hospitals which investigated the impact of concurrent administration of antibiotics on the incidence of catheter-associated urinary tract infection (UTI), showed that 61% of catheterized patients received antibiotics at some stage during bladder drainage. The use of antibiotics within 48 hours prior to catheter removal reduced the risk of bacteriuria fivefold. Multivariate analysis of patients who were catheterized for 3-14 days indicated that, apart from the duration of catheter employment, the use of antibiotics was the only variable significantly and independently associated with the development of bacteriuria. The power of this association varied inversely with increasing duration of catheterization but remained significant throughout the 3-14-day interval. Patients with bacteriuria at the time of catheter removal were more likely to have a febrile illness compared to those who remained free of catheter-associated UTI.

Once-daily dosing regimen for aminoglycoside plus beta-lactam combination therapy of serious bacterial infections: comparative trial with netilmicin plus ceftriaxone.

PURPOSE: Once-daily dosing of aminoglycosides has been suggested to improve their efficacy and reduce their toxicity. To test the clinical validity of this suggestion, we conducted a prospective, randomized trial comparing a conventional multiple-daily-dosing regimen of netilmicin with once-daily administration of the same total daily dose of this aminoglycoside. PATIENTS AND METHODS: We enrolled 141 predominantly elderly patients with severe bacterial infections. All patients received once-daily doses of 2 g ceftriaxone, in addition to netilmicin. RESULTS: Patients randomized to either of the two dosing strategies were comparable regarding age, APACHE II score, concomitant diseases, infection site, and rate of culture-proven bacteremia. Netilmicin treatment did not differ significantly in mean daily dose per kg body weight and days of therapy between the two treatment arms. Compared to patients receiving conventional doses, patients treated with a once-daily dose had higher serum peak netilmicin levels and lower trough levels. Outcome of infection and mortality were not influenced by dosing strategy. Although the overall incidence of nephrotoxicity was similar in both groups (16%), the occurrence of nephrotoxicity in patients treated with once-daily doses of netilmicin was significantly shifted to those given prolonged treatment, i.e., beyond 9 days. Auditory toxicity was documented in one patient treated with conventional doses and two patients treated with once-daily doses. CONCLUSION: Once-daily dosing of an aminoglycoside plus a long-acting cephalosporin in these patients constituted cost-effective and safe treatment for severe bacterial infections. Netilmicin-induced toxicity may be reduced by using once-daily dosing regimens and limiting the duration of treatment.