The role of postoperative prophylactic antibiotics in the treatment of facial fractures: a randomised, double-blind, placebo-controlled pilot clinical study. Part 1: orbital fractures in 62 patients

The aim of this study was to evaluate the difference between the effects of a 5-day and a 1-day course of antibiotics on the incidence of postoperative infection after displaced fractures of the orbit. A total of 62 patients with orbital blow-out fractures were randomly assigned to two groups, both of which were given amoxicillin/clavulanic acid 1.2g intravenously every 8h from the time of admission to 24h postoperatively. The 5-day group were then given amoxicillin/clavulanic acid 625mg orally every 8h for 4 further days. The 1-day group were given placebo orally at the same time intervals. Follow up appointments were 1, 2, 4, 6, and 12 weeks, and 6 months, postoperatively. An infection in the orbital region was the primary end point. Sixty of the 62 patients completed the study. Two of the 29 patients in the 5-day group (6.8%) and 1/31 patients in the 1-day group (3.2%) developed local infections. In the 5-day group 1 patient developed diarrhoea. In the 1-day group 1 patient developed a rash on the trunk. There were no significant differences in the incidence of infection or side effects between the groups. We conclude that in displaced orbital fractures a postoperative 1-day course of antibiotics is as effective in preventing infective complications as a 5-day regimen.

Genetic variations in bile acid homeostasis are not overrepresented in alcoholic cirrhosis compared to patients with heavy alcohol abuse and absent liver disease

Increased serum bile salt levels have been associated to a single-nucleotide polymorphism in the bile salt export pump (BSEP; ABCB11) in several acquired cholestatic liver diseases but there is little evidence in alcoholic liver disease (ALD). Furthermore, a crosstalk between vitamin D and bile acid synthesis has recently been discovered. Whether this crosstalk has an influence on the course of ALD is unclear to date. Our aim was to analyse the role of genetic polymorphisms in BSEP and the vitamin D receptor gene (NR1I1) on the emergence of cirrhosis in patients with ALD. Therefore, 511 alcoholic patients (131 with cirrhosis and 380 without cirrhosis) underwent ABCB11 genotyping (rs2287622). Of these, 321 (131 with cirrhosis and 190 without cirrhosis) were also tested for NR1I1 polymorphisms (bat-haplotype: BsmI rs1544410, ApaI rs7975232 and TaqI rs731236). Frequencies of ABCB11 and NR1I1 genotypes and haplotypes were compared between alcoholic patients with and without cirrhosis and correlated to serum bile salt, bilirubin and aspartate aminotransferase levels in those with cirrhosis. Frequencies of ABCB11 and NR1I1 genotypes and haplotypes did not differ between the two subgroups and no significant association between genotypes/haplotypes and liver function tests could be determined for neither polymorphism. We conclude that ABCB11 and NR1I1 polymorphisms are obviously not associated with development of cirrhosis in patients with ALD.

A systematic review of prophylactic antibiotics in the surgical treatment of maxillofacial fractures

PURPOSE: A systematic review was performed to find evidence for prophylactic administration of antibiotics in relation to treatment of maxillofacial fractures. METHODS: Four studies were retrieved that fulfilled most of the requirements of being randomized controlled clinical trials. RESULTS: An analysis of these studies showed a 3-fold decrease in the infection rate of mandibular fractures in the antibiotic treated groups compared with the control groups. A variety of antibiotics had been used with an apparently uniform effect. A "1-shot" regimen or a 1-day treatment course had a similar or perhaps even better effect than 7 days of treatment. No infections were related to condylar, maxillary, or zygoma fractures. CONCLUSION: A 1-shot or 1-day administration of prophylactic antibiotics seem to be the best documented to reduce infections in the management of mandibular fractures not involving the condylar region.

Validity and reliability of the German version of the short understanding of substance abuse scale

This paper presents the German version of the Short Understanding of Substance Abuse Scale (SUSS) [Humphreys et al.: Psychol Addict Behav 1996;10:38-44], the Verstandnis von Storungen durch Substanzkonsum (VSS), and evaluates its psychometric properties. The VSS assesses clinicians' beliefs about the nature and treatment of substance use disorders, particularly their endorsement of psychosocial and disease orientation. The VSS was administered to 160 treatment staff members at 12 substance use disorder treatment programs in the German-speaking part of Switzerland. Because the confirmatory factor analysis of the VSS did not completely replicate the factorial structure of the SUSS, an exploratory factor analysis was undertaken. This analysis identified two factors: the Psychosocial model factor and a slightly different Disease model factor. The VSS Disease and Psychosocial subscales showed convergent and discriminant validity, as well as sufficient reliability.

[Antibiotic resistance: infections of the upper respiratory tract and bronchi. When are antibiotics necessary?]

Antimicrobial resistance among respiratory tract pathogens has become an increasing problem worldwide during the last 10-20 years. The wide use of antimicrobial agents in ambulatory practice has contributed to the emergence and spread of antibiotic-resistant bacteria in the community, namely Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. The pneumococcus has developed resistance to most antibiotics used for its treatment. Classes with important resistance problems include the beta-lactams, the macrolides, the lincosamides, trimethoprim-sulfamethoxazole, and the tetracyclines. Unfortunately, resistance to more than one class of antibiotics is common. In Haemophilus influenzae and Moraxella catarrhalis, resistance to beta-lactam antibiotics is the main concern currently. It is important to know the local resistance pattern of the most common respiratory tract pathogens in order to make reasonable recommendations for an empirical therapy for respiratory tract infection, when antibiotic therapy is indeed indicated.

Comparative efficacies of antibiotics in a rat model of meningoencephalitis due to Listeria monocytogenes

The antibacterial activities of amoxicillin-gentamicin, trovafloxacin, trimethoprim-sulfamethoxazole (TMP-SMX) and the combination of trovafloxacin with TMP-SMX were compared in a model of meningoencephalitis due to Listeria monocytogenes in infant rats. At 22 h after intracisternal infection, the cerebrospinal fluid was cultured to document meningitis, and the treatment was started. Treatment was instituted for 48 h, and efficacy was evaluated 24 h after administration of the last dose. All tested treatment regimens exhibited significant activities in brain, liver, and blood compared to infected rats receiving saline (P < 0.001). In the brain, amoxicillin plus gentamicin was more active than all of the other regimens, and trovafloxacin was more active than TMP-SMX (bacterial titers of 4.1 +/- 0.5 log10 CFU/ml for amoxicillin-gentamicin, 5.0 +/- 0.4 log10 CFU/ml for trovafloxacin, and 5.8 +/- 0.5 log10 CFU/ml for TMP-SMX; P < 0.05). In liver, amoxicillin-gentamicin and trovafloxacin were similarly active (2.8 +/- 0.8 and 2.7 +/- 0.8 log10 CFU/ml, respectively) but more active than TMP-SMX (4.4 +/- 0. 6 log10 CFU/ml; P < 0.05). The combination of trovafloxacin with TMP-SMX did not alter the antibacterial effect in the brain, but it did reduce the effect of trovafloxacin in the liver. Amoxicillin-gentamicin was the most active therapy in this study, but the activity of trovafloxacin suggests that further studies with this drug for the treatment of Listeria infections may be warranted.

Quinolone antibiotics in therapy of experimental pneumococcal meningitis in rabbits

Using a rabbit model of pneumococcal meningitis, we compared the pharmacokinetics and bactericidal activities in cerebrospinal fluid (CSF) of older (ciprofloxacin, ofloxacin) and newer (levofloxacin, temafloxacin, CP-116,517, and Win 57273) quinolones with those of the beta-lactam ceftriaxone. All quinolones penetrated into the inflamed CSF better than ceftriaxone, and the speed of entry into CSF was closely related to their degrees of lipophilicity. At a dose of 10 mg/kg.h, which in the case of the quinolones already in use in clinical practice produced concentrations attainable in the sera and CSF of humans, ciprofloxacin had no antipneumococcal activity (delta log10 CFU/ml.h, +0.20 +/- 0.14). Ofloxacin (delta log10 CFU/ml.h, -0.13 +/- 0.12), temafloxacin (delta log10 CFU/ml.h, -0.19 +/- 0.18), and levofloxacin (delta log10 CFU/ml.h, -0.24 +/- 0.16) showed slow bactericidal activity (not significantly different from each other), while CP-116,517 (delta log10 CFU/ml.h, -0.59 +/- 0.21) and Win 57273 (delta log10 CFU/ml.h, -0.72 +/- 0.20) showed increased bactericidal activities in CSF that was comparable to that of ceftriaxone at 10 mg/kg.h (delta log10 CFU/ml.h, -0.80 +/- 0.17). These improved in vivo activities of the newer quinolones reflected their increased in vitro activities. All quinolones and ceftriaxone showed positive correlations between bactericidal rates in CSF and concentrations in CSF relative to their MBCs. Only when this ratio exceeded 10 did the antibiotics exhibit rapid bactericidal activities in CSF. In conclusion, in experimental pneumococcal meningitis the activities of new quinolones with improved antipneumococcal activities were comparable to that of ceftriaxone.

Pharmacodynamics of antibiotics in the therapy of meningitis: infection model observations

Detailed studies of pharmacodynamic principles relevant to the therapy of bacterial meningitis are difficult to perform in man, while the rabbit model of bacterial meningitis has proved to be extremely valuable and has led to insights that appear relevant for the treatment of humans. Most importantly in the light of the restricted penetration of antibiotics into the CSF, animal studies have shown that in meningitis there is a dose-response curve between the CSF concentrations achieved by antibiotics and their bactericidal activity. This appears to be true for all classes of antibiotics thus far examined, including the beta-lactams, which do not show such a dose-response behaviour in other infections. Only CSF concentrations that exceed the MBC of the infecting organism by at least 10-30-fold achieve consistent and rapid bactericidal activity. Such rapid bactericidal activity is a requirement for successful therapy with beta-lactams and can be impaired with certain antibiotics by the specific conditions in infected CSF (protein content; acidic pH; slow-growing bacteria). However, rapid antibiotic killing of the infecting organisms may not be without adverse effects either. Some antibiotics, particularly beta-lactams lead to the brisk liberation of bacterial cell wall components (e.g. endotoxin, in the case of Gram-negative organisms) which have an inflammatory effect on the host and can lead to a temporary deterioration of the disease. Dexamethasone, when administered with the antibiotic, can prevent some of the adverse effects of rapid bacterial lysis.

Antibacterial activity of beta-lactam antibiotics in experimental meningitis due to Streptococcus pneumoniae

In order to define the characteristics of the antibacterial activity of beta-lactam antibiotics in the treatment of bacterial meningitis, the relationship between cerebrospinal fluid (CSF) drug concentrations and the rate of bacterial killing was investigated for penicillin G and four new cephalosporins in an animal model of meningitis due to Streptococcus pneumoniae. All five drugs showed a significant correlation between increasing drug concentrations in CSF and increasing bactericidal rates. Minimal activity was observed in CSF at drug concentrations of approximately the broth minimal bactericidal concentration (MBC). Maximal activity occurred with CSF concentrations 10-30 times higher. In vitro tests did not reproduce the unique correlation of increasing drug concentrations and killing activity found in vivo. When evaluating new beta-lactam antibiotics for the treatment of bacterial meningitis, it is reasonable to establish a minimum standard of CSF drug concentrations of greater than or equal to 30 times the MBC against the infecting organism.

Pharmacodynamics of antibiotics in experimental bacterial meningitis--two sides to rapid bacterial killing in the cerebrospinal fluid

In bacterial meningitis, several pharmacodynamic factors determine therapeutic success--when defined as sterilization of the cerebrospinal fluid (CSF); (i) local host defense deficits require the use of bactericidal antibiotics; (ii) CSF antibiotic concentrations that are at least 10-fold above the MBC are necessary for maximal bactericidal activity; (iii) high CSF peak concentrations that lead to rapid bacterial killing appear more important than prolonged suprainhibitory concentrations, probably because very low residual levels in the CSF prevent bacterial regrowth even during relatively long dosing intervals; (iv) penetration of antibiotics into the CSF is significantly impaired by the blood-brain barrier, thus requiring high serum levels to achieve the CSF concentrations necessary for rapid bacterial killing. Beyond these principles, recent data suggest that rapid lytic killing of bacteria in the CSF may have harmful effects on the brain because of the release of biologically active bacterial products. The conflict between the need for rapid CSF sterilization and the harmful consequences of bacterial lysis must be addressed in the therapy of meningitis.

Abuse of vasoconstrictive eyedrops mimicking an ocular pemphigoid

To describe conjunctival histopathologic alterations induced by excessive chronic astringent use.

Prophylactic antibiotics or G-CSF for the prevention of infections and improvement of survival in cancer patients undergoing chemotherapy

BACKGROUND: Febrile neutropenia (FN) and other infectious complications are some of the most serious treatment-related toxicities of chemotherapy for cancer, with a mortality rate of 2% to 21%. The two main types of prophylactic regimens are granulocyte (G-CSF) or granulocyte-macrophage colony stimulating factors (GM-CSF); and antibiotics, frequently quinolones or cotrimoxazole. Important current guidelines recommend the use of colony stimulating factors when the risk of febrile neutropenia is above 20% but they do not mention the use of antibiotics. However, both regimens have been shown to reduce the incidence of infections. Since no systematic review has compared the two regimens, a systematic review was undertaken. OBJECTIVES: To compare the effectiveness of G-CSF or GM-CSF with antibiotics in cancer patients receiving myeloablative chemotherapy with respect to preventing fever, febrile neutropenia, infection, infection-related mortality, early mortality and improving quality of life. SEARCH STRATEGY: We searched The Cochrane Library, MEDLINE, EMBASE, databases of ongoing trials, and conference proceedings of the American Society of Clinical Oncology and the American Society of Hematology (1980 to 2007). We planned to include both full-text and abstract publications. SELECTION CRITERIA: Randomised controlled trials comparing prophylaxis with G-CSF or GM-CSF versus antibiotics in cancer patients of all ages receiving chemotherapy or bone marrow or stem cell transplantation were included for review. Both study arms had to receive identical chemotherapy regimes and other supportive care. DATA COLLECTION AND ANALYSIS: Trial eligibility and quality assessment, data extraction and analysis were done in duplicate. Authors were contacted to obtain missing data. MAIN RESULTS: We included two eligible randomised controlled trials with 195 patients. Due to differences in the outcomes reported, the trials could not be pooled for meta-analysis. Both trials showed non-significant results favouring antibiotics for the prevention of fever or hospitalisation for febrile neutropenia. AUTHORS' CONCLUSIONS: There is no evidence for or against antibiotics compared to G(M)-CSFs for the prevention of infections in cancer patients.

Neighborhood Disadvantage and Birth Weight: The Role of Perceived Danger and Substance Abuse

In this analysis we connect structural neighborhood conditions to birth outcomes through their intermediate effects on mothers’ perceptions of neighborhood danger and their tendency to abuse substances during pregnancy. We hypothesize that neighborhood poverty and racial/ethnic concentration combine to produce environments that mothers perceive as unsafe, thereby increasing the likelihood of negative coping behaviors (substance abuse). We expect these behaviors, in turn, to produce lower birth weights. Using data from the Fragile Families and Child Wellbeing Study, a survey of a cohort mothers and children born between 1998 and 2000 in large cities in the United States, we find little evidence to suggest that neighborhood circumstances have strong, direct effects on birth weight. Living in a neighborhood with more foreigners had a positive effect on birth weight. To the extent that neighborhood conditions influence birth weight, the effect mainly occurs through an association with perceived neighborhood danger and subsequent negative coping behaviors. Poverty and racial/ethnic concentration increase a mother’s sense that her neighborhood is unsafe. The perception of an unsafe neighborhood, in turn, associates with a greater likelihood of smoking cigarettes and using illegal drugs, and these behaviors have strong and significant effects in reducing birth weight. However, demographic characteristics, rather than perceived danger or substance abuse, mediate the influence of neighborhood characteristics on birth weight.