Roel P. Verkooyen

Once-daily dosing regimen for aminoglycoside plus β-Lactam combination therapy of serious bacterial infections: Comparative trial with netilmicin plus ceftriaxone☆

PURPOSEnOnce-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.nnnPATIENTS AND METHODSnWe enrolled 141 predominantly elderly patients with severe bacterial infections. All patients received once-daily doses of 2 g ceftriaxone, in addition to netilmicin.nnnRESULTSnPatients 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.nnnCONCLUSIONnOnce-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.

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.

Prospective randomized study of once-daily versus thrice-daily netilmicin regimens in patients with intraabdominal infections

One hundred and ninety-seven patients with intraabdominal infections were enrolled in a prospective randomized multicenter study of netilmicin administered once daily (n=98) versus thrice daily (n=99) in combination with tinidazole administered once daily. Randomization was achieved for the infection site, clinical severity score, daily and total netilmicin dose, and duration of treatment. The mean maximum peak and trough levels of netilmicin in serum were 21.1 and 1.3 mg/l respectively for once daily treated patients, and 10.0 and 2.3 mg/l for thrice daily treated patients (p<0.05 for both parameters). The clinical response did not differ between patients treated once daily and those treated thrice daily. Overall rates for clinical cure, improvement and failure of therapy were 77 %, 17 % and 6 % respectively. No significant differences were found between once daily and thrice daily regimens in the occurrence of auditory, vestibular and renal toxicity, overall rates being 5 %, 1 % and 10 % respectively. Impairment of renal function was significantly related to higher maximum netilmicin serum trough levels during therapy, a higher clinical severity score and advanced age. It is concluded that netilmicin given once daily is as effective and safe as the multiple dose regimen. However, monitoring of aminoglycoside serum through levels is still advisable, especially in the old and severely ill patient.

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.

Chlamydia pneumoniae and the risk for exacerbation in multiple sclerosis patients

In this prospective study of 73 relapsing remitting multiple sclerosis patients followed up for a mean of 1.7 years, the relation was tested between serologically defined Chlamydia pneumoniae (CP) infection periods and exacerbation rate. Episodes of serologically defined CP infections were observed in a subgroup, and these episodes were associated with increased risk for exacerbation. CP polymerase chain reaction was positive in most of the CP seropositive patients. No correlation was found between the anti–CP antibody increase and titers of control antibodies.

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.

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.