Kegg Pathway: Cephalosporins - oral agents

Euro Surveill. 2009; 14(33):
Dimiņa E, Kūla M, Caune U, Vīgante D, Liepiņs M, Zeidaka L, Nikitina O, Kūriņa D, Mironovska A, Dumpis U

Antibiotic resistance and nosocomial infections have recently been recognised as a growing threat in Latvian hospitals. We used a modified point prevalence study design to gain accurate information on the antibiotic prescription pattern and the prevalence of nosocomial infections in different hospital departments. A given department was observed on a given day in a given month (May) five years in a row. All antibiotic treatments, dose and route of administration were recorded, in addition to demographic data. The most commonly used antibiotic groups were first generation Cephalosporins (35.6-38.9%), broad-spectrum penicillins (17.5-23.0%), fluoroquinolones (8.4-14.5%) and aminoglycosides (7.7-12.6%). Cefazolin was the most commonly used antibiotic. Antibiotics were predominantly used intravenously. The proportion of oral administration varied from 15.1% to 21.8%. A large proportion (13.3%) of the antibiotics was administered without clear reason. The crude prevalence rate of infection treated with antibiotics was 19.3%. The average prevalence of nosocomial infections was found to be 3.6%. These prevalence studies provided an opportunity to compare hospitals and outline variations and problem areas. They indicated the main problems in antibiotic prescription: large interhospital variations in the choice of an antibiotic for the most common infections, frequent antibiotic use without clear reason, and predominant intravenous administration.

J Antimicrob Chemother. 2009 Sep; 64 Suppl 1: i29-36
Livermore DM

Antibiotic resistance is a major public health concern, with fears expressed that we shortly will run out of antibiotics. In reality, the picture is more mixed, improving against some pathogens but worsening against others. Against methicillin-resistant Staphylococcus aureus (MRSA)--the highest profile pathogen--the range of treatment options is expanding, with daptomycin, linezolid and tigecycline all launched, and telavancin, ceftobiprole, ceftaroline and dalbavancin anticipated. There is a greater problem with enterococci, especially if, as in endocarditis, bactericidal activity is needed and the isolate has high-level aminoglycoside resistance; nevertheless, daptomycin, telavancin and razupenem all offer cidal potential. Against Enterobacteriaceae, the rapid and disturbing spread of extended-spectrum beta-lactamases, AmpC enzymes and quinolone resistance is forcing increased reliance on carbapenems, with resistance to these slowly accumulating via the spread of metallo-, KPC and OXA-48 beta-lactamases. Future options overcoming some of these mechanisms include various novel beta-lactamase-inhibitor combinations, but none of these overcomes all the carbapenemase types now circulating. Multiresistance that includes carbapenems is much commoner in non-fermenters than in the Enterobacteriaceae, depending mostly on OXA carbapenemases in Acinetobacter baumannii and on combinations of chromosomal mutation in Pseudomonas aeruginosa. No agent in advanced development has much to offer here, though there is interest in modified, less-toxic, polymyxin derivatives and in the siderophore monobactam BAL30072, which has impressive activity against A. baumannii and members of the Burkholderia cepacia complex. A final and surprising problem is Neisseria gonorrhoeae, where each good oral agent has been eroded in turn and where there is now little in reserve behind the oral oxyimino Cephalosporins, to which low-level resistance is emerging.

J Pediatr Hematol Oncol. 2009 Sep; 31(9): 635-41
Gupta A, Swaroop C, Agarwala S, Pandey RM, Bakhshi S

BACKGROUND: Outpatient oral therapy is infrequently used in pediatric low-risk febrile neutropenia (LRFN) as there is insufficient data regarding its equivalence as compared with parenteral therapy. METHODS: This is a single institutional, randomized control trial in pediatric LRFN aged 2 to 15 years, in which 123 episodes in 88 patients were randomized to outpatient oral ofloxacin 7.5 mg/kg 12 hourly and amoxycillin-clavulanate 12.5 mg/kg 8 hourly or outpatient intravenous (IV) ceftriaxone 75 mg/kg and amikacin 15 mg/kg once daily after blood cultures. RESULTS: Out of 119 evaluable episodes, one-third were leukemia patients in maintenance and rest were solid tumors. Success was achieved in 55/61 (90.16%) and 54/58 (93.1%) in oral and IV arms, respectively, (P=0.56). There were 3 hospitalizations but no mortality. Median days to resolution of fever, absolute neutrophil count >500/mm(3) and antibiotic use were 3, 5, and 6 days in both arms. There were 5 blood culture isolates (3 gram-positive and 2 gram-negative bacteria). Failure of outpatient therapy was associated with perianal infections, bacteremia, febrile neutropenia onset before day 9 of chemotherapy in solid tumors and Vincristine, actinomycin-D, and cyclophosphamide chemotherapy for rhabdomyosarcoma. All gram-positive isolates were successes, whereas both gram-negative isolates were failures. Diarrhea in IV arm and Vincristine, actinomycin-D, and cyclophosphamide chemotherapy in the oral arm predicted failure in subgroup analysis. CONCLUSIONS: Outpatient therapy is efficacious and safe in pediatric LRFN. There was no difference in outcome in oral versus IV outpatient therapy. Amoxycillin-clavulanate and ofloxacin may be the oral regimen of choice.

Vojnosanit Pregl. 2009 Jul; 66(7): 544-50
Matijević S, Lazić Z, Kuljić-Kapulica N, Nonković Z

BACKGROUND/AIM: The most common cause of acute dental infections are oral streptococci and anaerobe bacteria. Acute dentoalveolar infections are usually treated surgically in combination with antibiotics. Empirical therapy in such infections usually requires the use of penicillin-based antibiotics. The aim of this study was to investigate the clinical efficiency of amoxicillin and cefalexin in the empirical treatment of acute odontogenic abscess and to assess the antimicrobial susceptibility of the isolated bacteria in early phases of its development. METHODS: This study included 90 patients with acute odontogenic abscess who received surgical treatment (extraction of a teeth and/or abscess incision) and were divided into three groups: two surgical-antibiotic groups (amoxicillin, cefalexin) and the surgical group. In order to evaluate the effects of the applied therapy following clinical symptoms were monitored: inflammatory swelling, trismus, regional lymphadenitis and febrility. In all the patients before the beginning of antibiotic treatment suppuration was suched out of the abscess and antibiotic susceptibility of isolated bacteria was tested by using the disk diffusion method. RESULTS: The infection signs and symptoms lasted on the average 4.47 days, 4.67 days, and 6.17 days in the amoxicillin, cefalexin, and surgically only treated group, respectively. A total of 111 bacterial strains were isolated from 90 patients. Mostly, the bacteria were Gram-positive facultative anaerobs (81.1%). The most common bacteria isolated were Viridans streptococci (68/111). Antibiotic susceptibility of isolated bacteria to amoxicillin was 76.6% and cefalexin 89.2%. CONCLUSION: Empirical, peroral use of amoxicillin or cefalexin after surgical treatment in early phase of development of dentoalveolar abscess significantly reduced the time of clinical symptoms duration in the acute odontogenic infections in comparison to surgical treatment only. Bacterial strains isolated in early stages of dentoalveolar abscess showed high sensitivity to amoxicillin and cefalexin.

Jpn J Antibiot. 2009 Apr; 62(2): 103-15
Yamagishi Y, Izumi K, Tanaka K, Watanabe K, Mikamo H

In Japan, as a measure to prevent puerperal infection, oral antimicrobial prophylaxis has been conducted after delivery in many maternity clinics. However, there are only a few reports on the evidence supporting the validity of antimicrobial prophylaxis following normal delivery. There is concern that unnecessary antimicrobial administration may be conducted in such clinics. In the present study, the puerperal females after normal delivery were placed on different treatments. A group of females received no oral antimicrobial administration. The remaining females were given cefteram pivoxil (CFTM-PI) in the two different doses. In this manner, we evaluated usefulness of antimicrobial prophylaxis. We compared three treatment groups with respect to the incidence of infection for the period until the first week after discharge, and obtained the following results: non-antimicrobial prophylaxis group (group A), 5.83%; antimicrobial prophylaxis group (group B), 1.77%; antimicrobial prophylaxis group (group C), 0%. In group B, the puerperal females were orally given CFTM-PI in a total daily dose of 300 mg, three times daily for three days. In group C, the puerperal females were orally given CFTM-PI in a total daily dose of 300 mg, three times daily for five days. The incidence of infection was the lowest in group C which was followed by group B and group A in this order and the significant intergroup difference was recognized (p=0.004). We also compared the total counts of bacteria, aerobes and anaerobes in lochia on the fifth day during the puerperal period with those on the first day in each treatment group. The decrease in bacterial count was the largest in group C, which was followed by group B and group A in this order. Compared with the total bacterial counts obtained on the first day, those obtained on the fifth day decreased significantly (p<0.001). The results of the present study showed usefulness of antimicrobial prophylaxis after normal delivery. As one of the factors, a significant decrease in the count of bacteria in lochia seems to contribute toward producing the satisfactory outcome.

Arch Dis Child. 2009 Aug; 94(8): 607-14
Karageorgopoulos DE, Valkimadi PE, Kapaskelis A, Rafailidis PI, Falagas ME

OBJECTIVE: To evaluate the effectiveness and safety of short-course antibiotic therapy for bacterial meningitis, by performing a meta-analysis of randomised controlled trials (RCT). REVIEW METHODS: PubMed and the Cochrane Central Register of Controlled Trials were searched for RCT on patients of all ages with community-acquired acute bacterial meningitis that compared treatment with the same antibiotics, in the same daily dosage, administered for a short course (up to 7 days) versus a longer course (2 days or more than corresponding short course). RESULTS: Five open-label RCT involving children (3 weeks to 16 years) were included. No difference was demonstrated between short-course (4-7 days) and long-course (7-14 days) treatment (intravenous ceftriaxone) regarding: end-of-therapy clinical success (five RCT, 383 patients, fixed effect model (FEM), odds ratio (OR) 1.24, 95% CI 0.73 to 2.11); long-term neurological complications (five RCT, 367 patients, FEM, OR 0.60, 95% CI 0.29 to 1.27); long-term hearing impairment (four RCT, 241 patients, FEM, OR 0.59, 95% CI 0.28 to 1.23); total adverse events (two RCT, 122 patients, FEM, OR 1.29, 95% CI 0.57 to 2.91); or secondary nosocomial infections (two RCT, 139 patients, random effects model, OR 0.45, 95% CI 0.05 to 3.71). The duration of hospitalisation was lower with short-course treatment (two RCT, 137 patients, FEM, weighted mean difference -2.17 days, 95% CI -3.85 to -0.50). The available data did not allow for analysis by causative organism. CONCLUSION: This meta-analysis of the rather limited available relevant data could not show differences between short and long-course antibiotic treatment for bacterial meningitis in children. Further research on this issue is required.

J Chemother. 2009 Aug; 21(4): 378-82
Mezzatesta ML, Gona F, Marchese G, Nicolosi D, Toscano MA, Stefani S, Nicoletti G

The time-kill method was used to determine the bactericidal activity of cefditoren compared with oral Cephalosporins, amoxicillin, amoxicillin/clavulanate and levofloxacin against a randomly selected group of strains isolated from community-acquired respiratory tract infections (CARTIs). Cefditoren was the only agent showing significant bactericidal activity (>or=3 log(10 )reduction of viable cells) within 4 h against all Streptococcus pneumoniae strains, both penicillin-susceptible (PEN S) or -resistant (PEN R), as well as against Streptococcus pyogenes, and Moraxella catarrhalis. Against beta-lactamase positive strains of Haemophilus influenzae, cefditoren was comparable to the quinolone and more active than other Cephalosporins at 24 h. Cefditoren showed the best killing kinetic profiles and this observation may be important when choosing an oral third-generation cephalosporin as initial or sequential therapy.

Zhonghua Nan Ke Xue. 2009 Jun; 15(6): 499-504
Wang DN, Luo ZH, Wang H

OBJECTIVE: To explore the influence of non-gonococcal Neisseria on the diagnosis and treatment of male genitourinary infection. METHODS: The samples of urethral exudates, prostatic secretions or/and semen were collected from 8 cases of male patients with acute urethritis or chronic prostatitis, then inoculated into gonococcal agar medium, blood agar medium, Sabouraud agar medium and Mycoplasma agar medium, respectively. Neisseria gonorrhoeae, Mycoplasmae, fungi and other bacteria were isolated, Chlamydiae examined by Gemenez staining, and the gram-negative diplococci from the samples identified by oxidase test, biochemical examination and drug sensitivity test. The PCR products of the cryptic plasmid pJD1 gene of the isolated strains were amplified for the identification of Neisseria gonorrhoeae. Based on the results of drug sensitivity tests, intravenous or oral antibiotics were selected for treatment. RESULTS: Eight strains of gram-negative diplococci were isolated in this study, 3 identified as N. mucosa, 4 as N. cinerea and the other 1 as N. lactamica. The PCR identification test of the cryptic plasmid pJD1 gene showed the same positive results in all the strains as in N. gonorrhoeae. The non-gonococcal Neisseria isolated from the male genital tract secretions exhibited a multidrug resistance, especially to quinolones and fosfomycin. All the symptoms disappeared and no pathogens were detected in the patients after a 7-day treatment with Cephalosporins or/and Minocycline. CONCLUSION: Some Neisseria species normally parasitizing the upper respiratory tract can also cause male genitourinary infections, such as gonorrhea-like urethritis and chronic prostatitis. Neisseria gonorrhea could be clinically and etiologically misdiagnosed through such conventional methods as morphological examination, oxidase test and PCR identification test of cryptic plasmid and other nonspecific genes. Intravenous and/or oral antibiotic medication based on the results of drug sensitivity tests can cure acute urethritis and chronic prostatitis induced by non-gonococcal Neisseria in males. Drug resistance of non-gonococcal Neisseria directly affects the success of treatment.

J Toxicol Sci. 2009; 34 Suppl 2: SP217-22
Ito T

Congenital disorders of metabolism show a wide spectrum of symptoms as a consequence of impairment of a certain metabolic pathway by mutated enzymes resulting in abnormal accumulation of enzyme substrates, deficiency of expected products, and abnormal burden to collateral metabolic pathways, etc. However, in some occasions, depending on which pathway up to what degree of disturbance, it can be asymptomatic until a certain kind of burden is placed on to the patient. Enzyme deficiency involved in pyrimidine degradation, such as Dihydropyrimidine dehydrogenase (DPD) and Dihydropyrimidinase (DHP), has been reported with convulsion or autism as symptoms, but many asymptomatic cases are also reported. However, when the patients are treated with 5-fluorouracil, a pyrimidine analogue anticancer drug, lethal side-effects can be seen even in asymptomatic patients. Some oral cephem antibiotics have pivalic acid side chain to increase absorption rate at intestine. These antibiotics degrade into active antibiotics and pivalic acid at the intestinal wall. This pivalic acid is carnitine-conjugated and excreted into urine. Carnitine acts as a carrier of long chain fatty acid to mitochondria and to beta-oxidation, thus an important molecule for energy production by beta-oxidation and maintenance of mitochondrial function. Because of this, long term administration of such antibiotics could induce depletion of carnitine from the body and lead to low ketotic hypoglycemia, convulsion and consciousness disturbance. This paper reports some possible serious side effects closely linked to drug metabolism.

Korean J Ophthalmol. 2009 Jun; 23(2): 108-11
Yoo C, Kim SK, Huh K, Oh J

A 48-year-old man presented with visual dimness in the right eye that had developed 2 weeks previously. Dilated fundus examination showed few vitreous cells and numerous yellow, placoid lesions in both eyes. His right eye had more severe serous retinal detachment involving the macula. Fluorescein angiography demonstrated early irregular hypofluorescence with late staining in the areas of the yellow placoid lesions. He started a regimen of 60 mg of oral prednisone daily. Two weeks later, a serologic fluorescent treponemal antigen absorption test was positive for Ig G and Ig M. He was referred to an infectious disease specialist for antibiotic therapy. A week later, he returned, having stayed on prednisone only and not having taken the internist's antibiotic prescription. Meanwhile, the chorioretinitis in his right eye, which had initially been at a more advanced stage, was resolved with the use of steroids. The chorioretinitis in his left eye, which was aggravated at an earlier stage, ultimately recovered. Our case had atypical courses such that one eye improved and the other worsened during the same steroid treatment period. This result was inconsistent with that of previous reports showing that oral steroid influences the clinical course of acute syphilitic posterior placoid chorioretinitis.

BMC Infect Dis. 2009; 9: 104
Bágyi K, Haczku A, Márton I, Szabó J, Gáspár A, Andrási M, Varga I, Tóth J, Klekner A

BACKGROUND: Post-operative pulmonary infection often appears to result from aspiration of pathogens colonizing the oral cavity. It was hypothesized that impaired periodontal status and pathogenic oral bacteria significantly contribute to development of aspiration pneumonia following neurosurgical operations. Further, the prophylactic effects of a single dose preoperative cefazolin on the oral bacteria were investigated. METHODS: A matched cohort of 18 patients without postoperative lung complications was compared to 5 patients who developed pneumonia within 48 hours after brain surgery. Patients waiting for elective operation of a single brain tumor underwent dental examination and saliva collection before surgery. Bacteria from saliva cultures were isolated and periodontal disease was scored according to type and severity. Patients received 15 mg/kg cefazolin intravenously at the beginning of surgery. Serum, saliva and bronchial secretion were collected promptly after the operation. The minimal inhibitory concentrations of cefazolin regarding the isolated bacteria were determined. The actual antibiotic concentrations in serum, saliva and bronchial secretion were measured by capillary electrophoresis upon completion of surgery. Bacteria were isolated again from the sputum of postoperative pneumonia patients. RESULTS: The number and severity of coexisting periodontal diseases were significantly greater in patients with postoperative pneumonia in comparison to the control group (p = 0.031 and p = 0.002, respectively). The relative risk of developing postoperative pneumonia in high periodontal score patients was 3.5 greater than in patients who had low periodontal score (p < 0.0001). Cefazolin concentration in saliva and bronchial secretion remained below detectable levels in every patient. CONCLUSION: Presence of multiple periodontal diseases and pathogenic bacteria in the saliva are important predisposing factors of postoperative aspiration pneumonia in patients after brain surgery. The low penetration rate of cefazolin into the saliva indicates that its prophylactic administration may not be sufficient to prevent postoperative aspiration pneumonia. Our study suggests that dental examination may be warranted in order to identify patients at high risk of developing postoperative respiratory infections.

J Antimicrob Chemother. 2009 Sep; 64(3): 630-4
Hitchcock J, Jepson AP, Main J, Wickens HJ

BACKGROUND: Outpatient and home parenteral antimicrobial therapy (OHPAT) is becoming increasingly commonplace in the UK, enabling those patients who would previously have been obliged to remain in hospital for intravenous treatment to be managed as outpatients or in their own homes. The OHPAT service at St Mary's Hospital, London, was established in 2004. This paper describes the types of infection, antimicrobial management and outcomes of patients referred to the service in the 3.5 years since its inception. PATIENTS AND METHODS: All inpatients were eligible for OHPAT, provided that they had a serious infection requiring parenteral therapy, were well enough to leave hospital and fulfilled other criteria. We initially used an outpatient clinic model, but as the service developed, treatment was often delivered in patients' homes, with the OHPAT team providing training and assessment of primary care staff. RESULTS: Four hundred and sixty-seven patients were referred to the service between September 2004 and April 2008. Of these, 273 received 303 courses of OHPAT, 48 were discharged on oral therapy and 3 patients declined outpatient therapy; the remaining 143 patients were deemed unsuitable for inclusion, most commonly because the patient was too unwell for discharge (28.7%) or their social situation was inappropriate (14.7%). Causative organisms were identified in two-thirds of cases, with methicillin-resistant Staphylococcus aureus implicated in one-third of these. Mean treatment length was 24 days (range 1-165 days), with 7394 inpatient bed-days saved. Less than 5% of patients were readmitted within 28 days with infection- or drug-related problems. There were no cases of Clostridium difficile-associated diarrhoea during or after outpatient treatment, despite extensive use of Cephalosporins and other broad-spectrum agents. Patients found the service highly satisfactory and felt that it had improved their quality of life during the treatment period. CONCLUSIONS: The introduction of the OHPAT service at St Mary's Hospital has proved to be of benefit to patients and hospital efficiency alike.

Antimicrob agents Chemother. 2009 Sep; 53(9): 4032-4
Pandori M, Barry PM, Wu A, Ren A, Whittington WL, Liska S, Klausner JD

Using a real-time PCR assay specific for a mosaic penA allele that has been associated with oral cephalosporin resistance in Asia, 54 available Neisseria gonorrhoeae isolates collected in San Francisco, CA, from January to October 2008 were analyzed. Five isolates tested positive for the mosaic penA gene by real-time PCR. DNA sequencing revealed two mosaic penA alleles (SF-A and SF-B). Isolates with SF-A and SF-B alleles possessed elevated MICs for the oral Cephalosporins cefpodoxime and cefixime.

J Travel Med. 2009 May-Jun; 16(3): 186-90
Wyss MN, Steffen R, Dhupdale NY, Thitiphuree S, Mutsch M

BACKGROUND: There is an ongoing debate as to whether patients with travelers' diarrhea (TD) should self-medicate with a travel kit in developing countries or whether they should consult local doctors. Thus, we have analyzed TD management conducted by local health professionals. METHODS: Practicing physicians recommended to tourists in Goa (India), Mombasa (Kenya), and Phuket (Thailand) were invited to participate in a cross-sectional questionnaire survey. Three TD case descriptions were presented, and suggested diagnostic and therapeutic procedures were analyzed. RESULTS: In each of the three locations, approximately 20 physicians (59 in total, response rate 95%) completed the questionnaires. oral rehydration was proposed by more than 80% of the physicians for mild cases of TD and for TD with vomiting, while 73% of them would have treated febrile TD patients orally and 17% would have used intravenous (IV) fluids. Antimicrobials, primarily fluoroquinolones, would have been prescribed for 61, 73, and 95%, respectively, of these three cases. Cephalosporins, aminoglycosides (usually IV gentamicin), IV amoxicillin, and once co-trimoxazole were recommended. Many medical doctors added nitroimidazole to the antibiotic therapy. Multiple symptomatic drugs would have been prescribed. The rate of invasive procedures (infusions, injections, and diagnostic venipuncture) would have ranged from 20% to 86% in the scenarios of the different patients. Mainly practitioners who owned a clinic would have hospitalized patients with TD. CONCLUSIONS: Many physicians in destination countries treat TD patients similarly to the treatments prescribed in the "Western world." A minority uses obsolete antimicrobials. Polypharmacy and the high rate of invasive procedures with a theoretical risk of nosocomial infection are of concern. Training initiatives for both local physicians and travelers might be beneficial, and the guidelines should be based on internationally accepted expert advice.

Curr Opin Infect Dis. 2009 Feb; 22(1): 87-91
Tapsall JW

PURPOSE OF REVIEW: Antibiotic resistance in Neisseria gonorrhoeae poses on-going problems for individual case management and disease control for gonorrhoea. Considerable reliance is now placed on third-generation Cephalosporins for the treatment of gonorrhoea following the loss of efficacy of penicillins and quinolones. Current clinical and laboratory perspectives on N. gonorrhoeae with decreased susceptibility to third-generation Cephalosporins are provided. RECENT FINDINGS: Treatment failures following therapy with the oral third-generation Cephalosporins cefixime and ceftibuten have been reported, but not with the injectable ceftriaxone. The gonococci involved have raised minimal inhibitory concentrations to these agents, including to ceftriaxone. The presence of multiple chromosomal changes form the basis for this 'resistance', prominent among which is a mosaic penicillin-binding protein 2 found in association with additional known and unknown mutations in other genes. The imprecise nature of laboratory criteria for detecting these gonococci means that the distribution and prevalence of these strains is also uncertain. SUMMARY: Concerns regarding the appearance of gonococci associated with treatment failure with oral Cephalosporins are increasing. The origins, causes and patterns of spread of these clinically resistant gonococci are reminiscent of the earlier experiences with quinolone-resistant gonococci. Preventive measures require simultaneous implementation of disease-control principles, coupled with those for antimicrobial resistance.

Antimicrob agents Chemother. 2009 Aug; 53(8): 3462-71
Bulitta JB, Landersdorfer CB, Kinzig M, Holzgrabe U, Sorgel F

Cefuroxime axetil is widely used to treat respiratory tract infections. We are not aware of a population pharmacokinetic (PK) model for cefuroxime axetil. Our objectives were to develop a semiphysiological population PK model and evaluate the pharmacodynamic profile for cefuroxime axetil. Twenty-four healthy volunteers received 250 mg oral cefuroxime as a suspension after a standardized breakfast. Liquid chromatography-tandem mass spectrometry was used for drug analysis, NONMEM and S-ADAPT (results reported) were used for parametric population PK modeling, and NPAG was used for nonparametric population PK modeling. Monte Carlo simulations were used to predict the duration for which the non-protein-bound-plasma concentration was above the MIC (fT(>MIC)). A model with one disposition compartment, a saturable and time-dependent drug release from the stomach, and fast drug absorption from the intestine yielded precise (r > 0.992) and unbiased curve fits and an excellent predictive performance. The apparent clearance was 21.7 liters/h (19.8% coefficient of variation [CV]) and the volume of distribution 38.7 liters (18.3% CV). Robust (>or=90%) probabilities of target attainment (PTAs) were achieved by 250 mg cefuroxime given every 12 h (q12h) or q8h for MICs of MIC) of >or=40% and for MICs of MIC) of >or=65%. For the >or=40% fT(>MIC) target, the PTAs for 250 mg cefuroxime q12h were >or=97.8% for Streptococcus pyogenes and penicillin-susceptible Streptococcus pneumoniae. Cefuroxime at 250 mg q12h or q8h achieved PTAs below 73% or 92%, respectively, for Haemophilus influenzae, Moraxella catarrhalis, and penicillin-intermediate S. pneumoniae for susceptibility data from various countries. Depending on the MIC distribution, 250 mg oral cefuroxime q8h instead of q12h should be considered, especially for more-severe infections that require near-maximal killing by cefuroxime.

Perit Dial Int. 2009 May-Jun; 29(3): 297-302
Davenport A

BACKGROUND: Over the past two decades, the rate of peritonitis in patients treated by peritoneal dialysis (PD) has been significantly reduced. However, peritonitis remains a major complication of PD, accounting for considerable mortality and hospitalization among PD patients. OBJECTIVE: To compare the outcome of peritonitis in a large unselected group of PD patients with that from single-center and selected groups. METHOD: We audited the outcome of peritonitis in PD patients attending the 12 PD units in the Thames area in 2002 and 2003. There were 538 patients on continuous ambulatory PD (CAPD) and 325 patients on automated PD (APD) and/or continuous cycling PD (CCPD) at the end of 2002, and 635 CAPD and 445 APD/CCPD patients at the end of 2003. RESULTS: There were 1467 episodes of PD peritonitis during the 2-year period, including 129 recurrent episodes, with the average number of months between peritonitis episodes being 14.7 for CAPD and 18.1 for APD/CCPD, p < 0.05. However there was considerable variation between units. Coagulase-negative staphylococcus (CoNS) was the most common cause, accounting for around 30% of all peritonitis episodes, including recurrences, followed by non-pseudomonas gram negatives and Staphylococcus aureus. Cure rates were 77.2% for CoNS, 46.6% for S. aureus, and 7.7% for methicillin-resistant S. aureus. The cure rate for pseudomonas was 21.4%, and other gram negatives 56.7%. In total, there were 351 episodes of culture-negative peritonitis, with an average cure rate of 76.9%. Cure rates were higher for those centers that used a combination of intraperitoneal gentamicin and Cephalosporins than those centers that used oral-based regimes. A total of 296 PD catheters were removed as a direct consequence of PD peritonitis: 121 due to gram-positive and 123 due to gram-negative organisms. Only 49 catheters were reinserted and the patients returned to PD. 52 patients died during or subsequent to their episode of PD peritonitis, with an overall mortality rate of 3.5%. CONCLUSION: This audit showed that, in a large unselected population of PD patients, the incidence of peritonitis was significantly greater than that reported in single-center short-term studies, and varied from unit to unit. Similarly, the success of treating PD peritonitis varied not only with the cause of the infection but also from unit to unit. PD peritonitis remains a major cause of patients discontinuing PD and switching to hemodialysis.

Pediatr Dent. 2009 Mar-Apr; 31(2): 145-8
Thibodeau B

The purpose of this report is to present the case of a patient wherein revascularization of the necrotic infected pulp space of an immature permanent maxillary central incisor tooth was induced in vivo by stimulation of a blood clot from the periapical tissues into the canal space. This was achieved after disinfecting the canal space with a topical antibiotic paste followed by inducing a blood clot scaffold from the periapical tissues. This treatment approach offers great potential to avoid the need for traditional apexification with calcium hydroxide or the need to achieve an artificial apical barrier with mineral trioxide aggregate. Furthermore, this treatment approach can help rescue infected immature teeth by physiologically strengthening the root walls.

Minerva Stomatol. 2009 May; 58(5): 233-45
Pappalardo S, Pollicino A, Cantalupo Milazzo D, Brutto D, Carlino V, Astuto M

Deep face and neck infections are potentially life threatening if they are not diagnosed in time and then treated quickly. This report describes a case of face and deep neck infection, associated with a semi-impacted and decayed wisdom tooth in a cardiopathic, immunosuppressed patient suffering from, diabetes, hypothyroidism, osteoporosis, breathlessness, chronic bronchitis, with oral, cutaneous and vaginal erythematous lichen, Cushing's Syndrome, penicillin allergy, subjected to past hypophysectomy. The swelling was, first of all, treated in urgency, with an intravenous antibiotic therapy and, immediately afterwards, the phlegmonous infiltration linked to the avulsion of the lower third molar was surgically drained. The patient was then treated with intravenous multiple antibiotics, with the aim of eradicating the predominating bacteria that was encountered in the microbiological culture test. A complete remission of the pathological picture was obtained .

J Chemother. 2009 Apr; 21(2): 170-80
Weiss G, Reimnitz P, Hampel B, Muehlhofer E, Lippert H,

This prospective, randomized, open, international, multicenter study of adults with complicated intra-abdominal infections (cIAI) compared the efficacy and safety of sequential intravenous (i.v.) to oral (p.o.) moxifloxacin 400 mg once daily, with that of i.v. ceftriaxone 2 g once daily, plus metronidazole 500 mg three times daily, followed by p.o. amoxicillin/clavulanate 625 mg three times daily. The primary efficacy variable was clinical cure at test of cure (TOC) (day 28-42 after study entry) in the per protocol (PP) population. Of 595 patients in the study, 511 patients were valid for PP analysis (246 moxifloxacin, 265 ceftriaxone/metronidazole). Sequential moxifloxacin was noninferior to the comparator regimen--clinical cure rates at TOC were 80.9% versus 82.3% (moxifloxacin versus ceftriaxone/metronidazole; 95% CI -8.9, 4.2%). The incidence of adverse events was comparable between the two treatment groups. Therefore, sequential moxifloxacin monotherapy is as effective and safe as combination therapy with i.v. ceftriaxone plus i.v. metronidazole followed by oral amoxicillin/clavulanate for the treatment of cIAI.