International guidelines for infectious diseases: a practical guide

A growing number of organisations have become involved in the development of guidelines for infectious diseases (ID). The degree of acceptation of guidelines varies from one country to another. Some of these national differences are determining the practices of prescribing antibiotics, and infection control both in hospitals and in the community. This review provides updated information on ID guideline programmes, in particular on the topic of antimicrobial therapy. It is aimed at clinicians, both in their role as care providers and as designers of local antibiotic guidelines (antibiotic booklets). Definitions are given and the process of development is discussed. International and national ID guideline programmes in the English language are presented. Many URLs provide access to the different websites where most guidelines can be downloaded free of charge

Comparative study of the effects of ceftizoxime, piperacillin, and piperacillin-tazobactam concentrations on antibacterial activity and selection of antibiotic-resistant mutants of Enterobacter cloacae and Bacteroides fragilis in vitro and in vivo in mixed-infection abscesses

The effects of ceftizoxime (CZX), piperacillin (PIP), and PIP-tazobactam (PT) concentrations on the antibacterial activity and selection of resistant mutants of Bacteroides fragilis and Enterobacter cloacae were investigated in vitro in a mixed-culture anaerobic time-kill study and in vivo in a mixed-infection abscess model. Mixed cultures were incubated for 24 h with 0.125 to 512 micro g of CZX per ml or 0.125 to 2,048 micro g of PIP or PT per ml. Mice were treated every 2 h for 24 h with CZX at 6 to 1,536 mg/kg/day or with PIP or PT at 24 to 6,144 mg/kg/day starting 30 min before inoculation with different B. fragilis-E. cloacae combinations. There was a good correlation between the in vitro and in vivo activities of the antibiotics and their MICs obtained with high inocula (10(8) CFU/ml). The respective 50% effective doses (milligrams per kilogram per day) with B. fragilis and E. cloacae 22491 were 771 and 521 for CZX, 416 and 643 for PIP, and 85 and 554 for PT, and with the B. fragilis-E. cloacae 032349 combination, they were 81 and 21 for CZX and 77 and 766 for PT. Resistant mutants of E. cloacae 22491 were preferentially selected in vitro with 2 to 64 micro g of CZX per ml and in vivo with CZX at 12 to 384 mg/kg/day. There was no preferential selection of CZX-resistant B. fragilis or E. cloacae 032349. For CZX-resistant E. cloacae 22491, we found a 16- to 512-fold increase in the MIC of CZX and increased MICs of other expanded-spectrum cephalosporins, owing in part to the production of a stably derepressed cephalosporinase. In vitro and in vivo, PT did not select resistant mutants of E. cloacae and B. fragilis. Results demonstrate the adverse microbiological outcome of choosing an expanded-spectrum cephalosporin like CZX for empirical treatment of mixed infections involving a susceptible Enterobacter strain

Persistent sterile leukocyturia is associated with impaired renal function in human immunodeficiency virus type 1-infected children treated with indinavir

BACKGROUND: Prolonged administration of indinavir is associated with the occurrence of a variety of renal complications in adults. These well-documented side effects have restricted the use of this potent protease inhibitor in children. DESIGN: A prospective study to monitor indinavir-related nephrotoxicity in a cohort of 30 human immunodeficiency virus type 1-infected children treated with indinavir. METHODS: Urinary pH, albumin, creatinine, the presence of erythrocytes, leukocytes, bacteria and crystals, and culture were analyzed every 3 months for 96 weeks. Serum creatinine levels were routinely determined at the same time points. Steady-

Direct molecular versus culture-based assessment of Gram-positive cocci in biopsies of patients with major abscesses and diabetic foot infections

Major abscesses and diabetic foot infections (DFIs) are predominant subtypes of complicated skin and skin structure infections (cSSSIs), and are mainly caused by Staphylococcus aureus and β-hemolytic streptococci. This study evaluates the potential benefit of direct pathogen-specific real-time polymerase chain reaction (PCR) assays in the identification of causative organisms of cSSSIs. One-hundred and fifty major abscess and 128 DFI biopsy samples were collected and microbial DNA was extracted by using the Universal Microbe Detection kit for tissue samples. Pathogen-specific PCRs were developed for S. aureus and its virulence factor Panton–Valentine leukocidin (PVL), Streptococcus pyogenes, S. agalactiae, S. dysgalactiae, and the S. anginosus group. Identification by pathogen-specific PCRs was compared to routine culture and both methods were considered as the gold standard for determination of the sensitivity and specificity of each assay. Direct real-time PCR assays of biopsy samples resulted in a 34 % higher detection of S. aureus, 37 % highe

Effect of recombinant murine granulocyte colony-stimulating factor with or without fluoroquinolone therapy on mixed-infection abscesses in mice.

The aim of the study was to determine if immunomodulation of host defense with recombinant murine granulocyte colony-stimulating factor (G-CSF) improves the efficacy of trovafloxacin or moxifloxacin in abscesses containing Bacillus fragilis ATCC 23745 and different Escherichia coli strains varying in virulence. Treatment of mice inoculated with 10(7) CFU B. fragilis and 10(5) CFU low-virulence E. coli with either trovafloxacin (150 mg/kg/day every 24 hours, days 3 to 7) or moxifloxacin (96 mg/kg/day every 12 hours, days 3 to 7), significantly reduced the number of B. fragilis to 6.9 +/- 0.35 and 5.8 +/- 0.10 and that of E. coli to 4.9 +/- 0.09 and 4.2 +/- 0.07 log CFU/abscess for trovafloxacin and moxifloxacin, respectively, compared to controls (B. fragilis 8.7 and E. coli 7.4 log CFU/abscess) on day 8. Also, moxifloxacin was more potent than trovafloxacin. Addition of G-CSF prophylaxis (1 mug once on day -1) or therapy (1 mug/day on days 3 to 7) to fluoroquinolone treatment did not improve the efficacy of fluoroquinolone therapy alone. The effect of moxifloxacin with or without G-CSF prophylaxis on abscesses with a virulent hemolytic E. coli strain was also studied. In moxifloxacin-treated mice, 75% survived infection compared to 10% of controls. Combining moxifloxacin with G-CSF prophylaxis significantly decreased survival (30%) compared to moxifloxacin alone. In addition, G-CSF prophylaxis resulted in a threefold (E. coli) to 100-fold (B. fragilis) increased outgrowth in the abscesses of surviving mice. In conclusion, the addition of G-CSF to a fluoroquinolone is not advisable since, depending on the virulence of the E. coli strains, this might detrimentally influence the outcome of therapy

Colonization and resistance dynamics of gram-negative bacteria in patients during and after hospitalization.

The colonization and resistance dynamics of aerobic gram-negative bacteria in the intestinal and oropharyngeal microfloras of patients admitted to intensive care units (ICU) and general wards were investigated during and after hospitalization. A total of 3,316 specimens were obtained from patients upon admission, once weekly during hospitalization, at discharge from the ICU, at discharge from the hospital, and 1 and 3 months after discharge from the hospital. Five colonies per specimen were selected for identification and susceptibility testing. In both patient populations, the gram-negative colonization rates in oropharyngeal specimens increased during hospitalization and did not decrease in the 3 months after discharge. In rectal specimens, colonization rates decreased during hospitalization and increased after discharge. There was a change in species distribution among the dominant microfloras during hospitalization. Klebsiella spp., Enterobacter spp., Serratia marcescens, and Pseudomonas aeruginosa were isolated more often, whereas the frequency of Escherichia coli declined. The percentage of ICU patients colonized with ampicillin- and/or cephalothin-resistant fecal E. coli was significantly increased at discharge from the hospital and did not change in the 3 months after discharge. The emergence of multidrug resistance was observed for E. coli during patient stays in the ICU. Resistance frequencies in E. coli significantly increased with the length of stay in the ICU. For the general ward population, no significant changes in resistance frequencies were found during hospitalization. From a population perspective, the risk of dissemination of resistant gram-negative bacteria into the community through hospitalized patients appears to be low for general ward patients but is noticeably higher among ICU patients

Risk factors for urological symptoms in a cohort of users of the HIV protease inhibitor indinavir sulfate: The ATHENA cohort

Background: Nephrolithiasis is a well-known complication of indinavir treatment and may result in urological symptoms ranging from renal colic to renal insufficiency. Objective: To obtain further knowledge regarding the incidence and risk factors of urological symptoms associated with indinavir sulfate use. Methods: This study was performed in the ATHENA (AIDS Therapy Evaluation National AIDS Therapy Evaluation Centre) cohort of patients infected with human immunodeficiency virus (HIV) receiving antiretroviral therapy in the Netherlands. The incidence rate of urological symptoms was assessed in a subcohort of 1219 patients starting HIV protease inhibitor treatment after 1996. Urological symptoms were defined as an initial report of nephrolithiasis, renal colic, flank pain, hematuria, renal insufficiency, or nephropathy. Using multivariate Cox regression analysis, risk factors for urological symptoms during indinavir treatment were subsequently studied among the subset of 644 patients who started indinavir treatment after 1996. Results: The incidence of urological symptoms was 8.3 per 100 treatment-years for indinavir vs 0.8 per 100 treatment-years for other HIV protease inhibitors. Risk factors for urological symptoms during indinavir treatment were low weight (relative risk [RR], 2.1; 95% confidence interval [CI], 1.1-3.9), low lean body mass (RR, 1.7;95% CI, 1.0-2.9), undetectable HIV-1 RNA when starting indinavir treatment (RR, 3.2;95% CI, 1.5-6.0), prior treatment change because of intolerance (RR, 2.4;95% CI, 1.2-5.1), indinavir regimens of 1000 mg or more twice daily (RR, 3.1;95% CI, 1.3-8.2), and warm environmental temperatures (RR, 3.9;95% CI, 1.7-8.8). Risk estimates were highest among patients with a low lean body mass. Conclusion: Increased alertness for urological symptoms is warranted for patients starting indinavir treatment, particularly among those with a low lean body mass, during indinavir regimens of 1000 mg or more twice daily, and in warm weather environments