Do dietary interventions exert clinically important effects on the bioavailability of ß-lactam antibiotics? A systematic review with meta-analyses.

BACKGROUND: Managing drug-food interactions may help to achieve the optimal action and safety profile of ß-lactam antibiotics. METHODS: We conducted a systematic review with meta-analyses in adherence to PRISMA guidelines for 32 ß-lactams. We included 166 studies assessing the impact of food, beverages, antacids or mineral supplements on the pharmacokinetic (PK) parameters or PK/pharmacodynamic (PK/PD) indices. RESULTS: Eighteen of 25 ß-lactams for which data on food impact were available had clinically important interactions. We observed the highest negative influence of food (AUC or Cmax decreased by >40%) for ampicillin, cefaclor (immediate-release formulations), cefroxadine, cefradine, cloxacillin, oxacillin, penicillin V (liquid formulations and tablets) and sultamicillin, whereas the highest positive influence (AUC or Cmax increased by >45%) for cefditoren pivoxil, cefuroxime and tebipenem pivoxil (extended-release tablets). Significantly lower bioavailability in the presence of antacids or mineral supplements occurred for 4 of 13 analysed ß-lactams, with the highest negative impact for cefdinir (with iron salts) and moderate for cefpodoxime proxetil (with antacids). Data on beverage impact were limited to 11 antibiotics. With milk, the extent of absorption was decreased by >40% for cefalexin, cefradine, penicillin G and penicillin V, whereas it was moderately increased for cefuroxime. No significant interaction occurred with cranberry juice for two tested drugs (amoxicillin and cefaclor). CONCLUSIONS: Factors such as physicochemical features of antibiotics, drug formulation, type of intervention, and patient's health state may influence interactions. Due to the poor actuality and diverse methodology of included studies and unproportionate data availability for individual drugs, we judged the quality of evidence as low.

Well-Orientation Strategy Biosynthesis of Cefuroxime-Silver Nanoantibiotic for Reinforced Biodentine™ and Its Dental Application against Streptococcus mutans.

Dental caries results from the bacterial pathogen Streptococcus mutans (S. mutans) and is the maximum critical reason for caries formation. Consequently, the present study aims to evaluate the antibacterial activity of a newly synthesized nanoantibiotic-Biodentine formulation. The silver nanoparticles (ROE-AgNPs) were biosynthesized from the usage of Rosmarinus officinalis L. extract (ROE) and conjugated with cefuroxime to form Cefuroxime-ROE-AgNPs. Using Biodentine™ (BIOD), five groups of dental materials were prepared, in which Group A included conventional BIOD, Group B included BIOD with ROE-AgNPs, Groups C and D included BIOD with Cefuroxime-ROE-AgNPs at concentrations of 0.5% and 1.5% cefuroxime, respectively, and Group E included BIOD with 1.5% cefuroxime. The synthesized ROE-AgNPs or Cefuroxime-ROE-AgNPs were characterized for conjugating efficiency, morphology, particle size, and in vitro release. Minimum inhibitory concentration (MIC) of the cefuroxime, ROE-AgNPs, and Cefuroxime-ROE-AgNPs were additionally evaluated against cefuroxime resistant S. mutans, which furthered antibacterial efficacy of the five groups of dental materials. The UV-Visible spectrum showed the ROE-AgNPs or Cefuroxime-ROE-AgNPs peaks and their formation displayed through transmission electron microscopy (TEM), X-ray diffraction (XRD) pattern, and Fourier transforms infrared (FTIR) analysis. The end result of Cefuroxime-ROE-AgNPs showed conjugating efficiency up to 79%. Cefuroxime-ROE-AgNPs displayed the highest antibacterial efficacy against S. mutans as compared to cefuroxime or ROE-AgNPs alone. Moreover, the MIC of ROE-AgNPs and Cefuroxime-ROE-AgNPs was detected against S. mutans to be 25 and 8.5 µg/mL, respectively. Consequently, Cefuroxime-ROE-AgNPs displayed that a decrease in the MIC reached to more than three-fold less than MIC of ROE-AgNPs on the tested strain. Moreover, Cefuroxime-ROE-AgNPs/BIOD was employed as a novel dental material that showed maximum antimicrobial activity. Groups C and D of novel materials showed inhibitory zones of 19 and 26 mm, respectively, against S. mutans and showed high antimicrobial rates of 85.78% and 91.17%, respectively. These data reinforce the utility of conjugating cefuroxime with ROE-AgNPs to retrieve its efficiency against resistant S. mutant. Moreover, the nanoantibiotic delivered an advantageous antibacterial effect to BIOD, and this may open the door for future conjugation therapy of dental materials against bacteria that cause dental caries.

Colo-Pro: a pilot randomised controlled trial to compare standard bolus-dosed cefuroxime prophylaxis to bolus-continuous infusion-dosed cefuroxime prophylaxis for the prevention of infections after colorectal surgery.

Standard bolus-dosed antibiotic prophylaxis may not inhibit growth of antibiotic resistant colonic bacteria, a cause of SSIs after colorectal surgery. An alternative strategy is continuous administration of antibiotic throughout surgery, maintaining concentrations of antibiotics that inhibit growth of resistant bacteria. This study is a pilot comparing bolus-continuous infusion with bolus-dosed cefuroxime prophylaxis in colorectal surgery. This is a pilot randomised controlled trial in which participants received cefuroxime bolus-infusion (intervention arm) targeting free serum cefuroxime concentrations of 64 mg/L, or 1.5 g cefuroxime as a bolus dose four-hourly (standard arm). Patients in both arms received metronidazole (500 mg intravenously). Eligible participants were adults undergoing colorectal surgery expected to last for over 2 h. Results were analysed on an intention-to-treat basis. The study was successfully piloted, with 46% (90/196) of eligible patients recruited and 89% (80/90) of participants completing all components of the protocol. A trialled bolus-continuous dosing regimen was successful in maintaining free serum cefuroxime concentrations of 64 mg/L. No serious adverse reactions were identified. Rates of SSIs (superficial and deep SSIs) were lower in the intervention arm than the standard treatment arm (24% (10/42) vs. 30% (13/43)), as were infection within 30 days of operation (41% (17/43) vs 51% (22/43)) and urinary tract infections (2% (1/42) vs. 9% (4/43)). These infection rates can be used to power future clinical trials. This study demonstrates the feasibility of cefuroxime bolus-continuous infusion of antibiotic prophylaxis trials, and provides safety data for infusions targeting free serum cefuroxime concentrations of 64 mg/L. Trial registration: NCT02445859 .

Changes in Bacterial Resistance Patterns of Pediatric Urinary Tract Infections and Rationale for Empirical Antibiotic Therapy.

BACKGROUND: The causative agent spectrum and resistance patterns of urinary tract infections in children are affected by many factors. AIMS: To demonstrate antibiotic resistance in urinary tract infections and changing ratio in antibiotic resistance by years. STUDY DESIGN: Retrospective cross-sectional study. METHODS: We analysed antibiotic resistance patterns of isolated Gram (-) bacteria during the years 2011-2014 (study period 2) in children with urinary tract infections. We compared these findings with data collected in the same centre in 2001-2003 (study period 1). RESULTS: Four hundred and sixty-five uncomplicated community-acquired Gram (-) urinary tract infections were analysed from 2001-2003 and 400 from 2011-2014. Sixty-one percent of patients were female (1.5 girls : 1 boy). The mean age of children included in the study was 3 years and 9 months. Escherichia coli was the predominant bacteria isolated during both periods of the study (60% in study period 1 and 73% in study period 2). Bacteria other than E. coli demonstrated a higher level of resistance to all of the antimicrobials except trimethoprim-sulfamethoxazole than E. coli bacteria during the years 2011-2014. In our study, we found increasing resistance trends of urinary pathogens for cefixime (from 1% to 15%, p<0.05), amikacin (from 0% to 4%, p<0.05) and ciprofloxacin (from 0% to 3%, p<0.05) between the two periods. Urinary pathogens showed a decreasing trend for nitrofurantoin (from 17% to 7%, p=0.0001). No significant trends were detected for ampicillin (from 69% to 71%), amoxicillin-clavulanate (from 44% to 43%), cefazolin (from 39% to 32%), trimethoprim-sulfamethoxazole (from 32% to 31%), cefuroxime (from 21% to 18%) and ceftriaxone (from 10% to 14%) between the two periods (p>0.05). CONCLUSION: In childhood urinary tract infections, antibiotic resistance should be evaluated periodically and empiric antimicrobial therapy should be decided according to antibiotic sensitivity results.

Coupling Data Mining and Laboratory Experiments to Discover Drug Interactions Causing QT Prolongation.

BACKGROUND: QT interval-prolonging drug-drug interactions (QT-DDIs) may increase the risk of life-threatening arrhythmia. Despite guidelines for testing from regulatory agencies, these interactions are usually discovered after drugs are marketed and may go undiscovered for years. OBJECTIVES: Using a combination of adverse event reports, electronic health records (EHR), and laboratory experiments, the goal of this study was to develop a data-driven pipeline for discovering QT-DDIs. METHODS: 1.8 million adverse event reports were mined for signals indicating a QT-DDI. Using 1.6 million electrocardiogram results from 380,000 patients in our institutional EHR, these putative interactions were either refuted or corroborated. In the laboratory, we used patch-clamp electrophysiology to measure the human ether-à-go-go-related gene (hERG) channel block (the primary mechanism by which drugs prolong the QT interval) to evaluate our top candidate. RESULTS: Both direct and indirect signals in the adverse event reports provided evidence that the combination of ceftriaxone (a cephalosporin antibiotic) and lansoprazole (a proton-pump inhibitor) will prolong the QT interval. In the EHR, we found that patients taking both ceftriaxone and lansoprazole had significantly longer QTc intervals (up to 12 ms in white men) and were 1.4 times more likely to have a QTc interval above 500 ms. In the laboratory, we found that, in combination and at clinically relevant concentrations, these drugs blocked the hERG channel. As a negative control, we evaluated the combination of lansoprazole and cefuroxime (another cephalosporin), which lacked evidence of an interaction in the adverse event reports. We found no significant effect of this pair in either the EHR or in the electrophysiology experiments. Class effect analyses suggested this interaction was specific to lansoprazole combined with ceftriaxone but not with other cephalosporins. CONCLUSIONS: Coupling data mining and laboratory experiments is an efficient method for identifying QT-DDIs. Combination therapy of ceftriaxone and lansoprazole is associated with increased risk of acquired long QT syndrome.

Iontophoresis of amoxicillin and cefuroxime: rapid therapeutic concentrations in skin.

CONTEXT: Amoxicillin (AMX) and cefuroxime (CFX) are antibiotics used often to treat skin bacterial infections. Typically, high oral doses are required to achieve minimum inhibitory concentration (MIC) at the site of infection that may affect only a very small area of skin. OBJECTIVES: To lower side effects and increase therapeutic effectiveness, the percutaneous absorption and retention of AMX and CFX administered by iontophoresis was investigated in a rabbit model by measuring dermis concentrations via microdialysis. METHODS: Iontophoresis was performed using a stainless steel electrode and a non-woven polypropylene pad. The cartridge pad was soaked with a solution of AMX in glycerin or of CFX in glycerin/water (60:40). Constant current density of 0, 100, 200 or 300 µA/cm(2) was applied for 60 min. RESULTS: For AMX, therapeutically effective skin concentrations were detected immediately after the application of electrical current for any of the current density tested and remained above it for at least 2 h from the end of iontophoresis. For CFX, skin concentrations rose above MIC only at the higher current densities and fell below the MIC by the end of the experiment. CONCLUSION: Iontophoresis is a promising method to obtain a fast and sustained concentration of AMX and CFX in skin.

In vitro compatibility study of cephalosporin with intraocular irrigating solutions and intracameral medications.

BACKGROUND: To study the compatibility of cephalosporins with intraocular irrigating solutions and intracameral medications commonly used in cataract surgery. DESIGN: The was an in vitro experiment conducted in the Research Laboratory of the Department of Microbiology, the Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong. SAMPLES: Three cephalosporins--cefazolin, cefuroxime and ceftazidime--were separately diluted and mixed with irrigating solutions and intracameral medications to form 192 samples and 12 control solutions. METHODS: The cephalosporins were dissolved in normal saline and further diluted to the concentration of 1 mg in 0.1 mL with normal saline, Ringer's solution, balanced salt solution and fortified balanced salt solutions. These were mixed with balanced salt solutions or fortified balanced salt solutions, with adrenaline, acetylcholine or carbachol and kept at 37°C for 2 h. The concentrations of free cephalosporins were measured with rapid high-performance liquid chromatography at baseline (0 h) and at 2 h. MAIN OUTCOME MEASURES: Free concentrations of cephalosporins at 2 h were compared with mean baseline (0 h) value. A difference of 3 standard deviations or more was considered statistically significant. RESULTS: At 2 h there was a significant drop in the cefuroxime concentration in preparations in which cefuroxime was diluted with normal saline (P < 0.01). In all preparations, the final concentrations of cephalosporins were higher than the minimal inhibitory concentrations (MIC(90)) for microbials commonly isolated from the external eye. CONCLUSION: Cefazolin, cefuroxime and ceftazidime were compatible with irrigating solutions and intracameral medications commonly used in cataract surgery.

In vivo selection of OmpK35-deficient mutant after cefuroxime therapy for primary liver abscess caused by Klebsiella pneumoniae.

OBJECTIVES: The aim of the study was to characterize the genetic basis of beta-lactam resistance developed in clinical isolates of Klebsiella pneumoniae after exposure to cefuroxime. METHODS: Clinical features of two episodes of liver abscess caused by K. pneumoniae in a diabetic patient were reported. Four isolates (KP(1)/KP(2) and KP(3)/KP(4)) of K. pneumoniae were recovered from cultures of blood/pus in the first and second episodes, respectively. Laboratory investigation of the K. pneumoniae isolates included genotyping by PFGE, resistance gene analysis by PCR amplification and DNA sequencing, and outer membrane protein analysis by SDS-PAGE. RESULTS: KP(3) and KP(4) were recovered after a 21 day cefuroxime therapy and demonstrated identical genotypes to that of KP(1) and KP(2). However, compared with KP(1) and KP(2), emerging resistance to piperacillin, cefalotin, cefuroxime and cefoxitin was observed. The other antibiotics tested, except ampicillin, retained the same effectiveness against the four isolates, although increases (4- to 8-fold) in the MICs of cefotaxime, ceftriaxone, ceftazidime, cefepime, flomoxef and aztreonam were observed in KP(3) and KP(4). None of the isolates produced extended-spectrum beta-lactamases or plasmid-mediated AmpC beta-lactamases. Deficiency in the expression of an outer membrane protein (OmpK35) was observed in the cefuroxime-resistant isolates, KP(3) and KP(4). CONCLUSIONS: The increased resistance to cephalosporins in these clinical isolates of K. pneumoniae after exposure to cefuroxime might be related to the loss of OmpK35.

Antibióticos profilácticos en cirugía urológica / Prophylactics antibiotics in urologic surgery

La infección es la complicación más temida de las cirugías, si bien éstas pueden presentarse en sitios alejados al operado, como el caso de las neumonías, lo más frecuente es que se relacione con la zona intervenida y en particular con la herida operatoria. Se prefiere hablar de Infección del Sitio Operatorio (ISO) en forma técnica para referirnos a esta afección. Se define como ISO: Infecciones que ocurren dentro de los 30 días después de la cirugía si no hay un implante o dentro de un año si hay un implante in situ. Además la infección parece, clínicamente, estar relacionada con la cirugía.

[The impact of antibiotic use on hospital-acquired pneumonia: data of etiology tests]. / Antibiotiku poveikis hospitalines pneumonijos etiologijos tyrimu duomenims.

AIM OF THE STUDY: To investigate most common pathogens isolated from the hospital-acquired pneumonia patients bronchoalveolar lavage fluid in Kaunas University of Medicine Hospital according to the previous antibiotic use and to estimate pathogens antibacterial susceptibility. MATERIALS AND METHODS: Results of 87 hospital-acquired pneumonia patients bronchoalveolar lavage fluid quantitative cultures were analyzed. Microorganisms isolated in clinically significant amount were considered as the etiological agents and included into analysis. Susceptibility was tested using the standard methods. Previously untreated patients were considered if the antibacterials were not administered at all or were used less than for 24 hours. RESULTS: H. influenzae isolation in significant amount rates were higher in previously untreated patients group comparing to previously treated (29.2%. (n=14) and 5.1% (n=2), respectively, p<0.05). Non-fermenters (P. aeruginosa and Acinetobacter spp.) isolation rates were higher in those previously treated comparing to untreated patients - (31.0% (n=13) and 4.2% (n=2), respectively, p<0.05). All H. influenzae strains were susceptible to ampicillin and cefuroxime. 22.2-44.4% of P. aeruginosa strains were resistant to ceftazidime, amikacin and ciprofloxacin. Estimated Acinetobacter spp. resistance to ciprofloxacin and gentamycin was 83.3% and to ampicillin/sulbactam - 16.7%. All methicillin-susceptible S.aureus were also susceptible to gentamycin and fucidin and methicillin resistant to rifampicin and vancomycin. CONCLUSIONS: Previous antibiotic treatment has an impact on pneumonia etiology testing. H. influenzae strains are more common isolated hospital-acquired pneumonia etiologic agents in previously untreated patients. The low antibacterial resistance was found enabling the use of aminopenicillins for treatment if H. influenzae infection suggested. The use of antibacterials increases non-fermenters isolation rates and combined antipseudomonal treatment is reasonable in these patients.

Database-driven computerized antibiotic decision support: novel use of expert antibiotic susceptibility rules embedded in a pathogen-antibiotic logic matrix.

To better serve an antibiotic guidance program, we hypothesized that the relatively few antibiotic susceptibility measurements conducted in the microbiology laboratory could be extended to predict antibiotic susceptibilities for all antibiotics on the hospital formulary using expert infectious disease logic. With the assistance of infectious disease specialists, we developed these logic rules and then applied them to 26,196 unique patient culture specimens and the accompanying 334,131 antibiotic susceptibility measurements generating 804,809 additional predicted bug-drug susceptibility data points. From the resulting data set, the antibiotic susceptibility profile for one pathogen, Streptococcus pneumoniae, is highlighted herein. We then incorporated the extended susceptibility profiles into a computerized antibiotic guidance program that matches current patients of interest with the positive cultures from past similar patients and calculates predicted effective antibiotic therapy. We conclude that this method successfully derives antibiotic predictions and merits further testing to evaluate its potential use in the hospital environment.

A simple infection model using pre-colonized implants to reproduce rat chronic Staphylococcus aureus osteomyelitis and study antibiotic treatment.

Staphylococcus aureus biofilms formed on medical implants represent a serious problem, being difficult to eradicate with antibiotic therapy and leading to chronic infections. Simplified in vivo and in vitro antibiotic susceptibility assays using biofilm bacteria are needed. In this work, a novel chronic osteomyelitis infection model was developed in rats in the absence of bacterial suspension, requiring the use of only 10(6) bacteria in biofilms at the site of surgery, with a full success in reproducing infection. Stainless-steel implants pre-colonized for 12 h with a highly adherent S. aureaus isolate were introduced into the rat tibiae. In animals not submitted to antibiotic treatment, infection was found in the implants and spread to bone in all cases, indicating the high efficacy of the model to reproduce osteomyelitis. The effect of a 21-day treatment with cefuroxime, vancomycin, tobramycin or ciprofloxacin on infection was studied in this model 42 days after surgery. Bone colonization was inhibited by vancomycin and cefuroxime. Cefuroxime (the most efficient antibiotic, able to sterilize 1 out of 8 implants) reduced the number of bacteria in biofilms adhered to implants at a higher extent than vancomycin, trobramycin and ciprofloxacin. Analogous observations were made in this work in vivo and in vitro on the relative antibiotic efficacy against S. aureus biofilm bacteria. suggesting the usefulness of both tests as a potential tool to study antibiotic suceptibility, and the need for new antimicrobials against these bacteria.

Successful shortening from seven to four days of parenteral beta-lactam treatment for common childhood infections: a prospective and randomized study.

OBJECTIVES: To explore whether 4-day parenteral beta-lactam therapy is as effective as 7-day therapy for children hospitalized for parenteral antimicrobials. METHODS: A series of patients aged 3 months to 15 years who fulfilled strict criteria for bacterial pneumonia, other respiratory infections, sepsis-like infections, and other acute infections were prospectively randomized to receive parenteral penicillin or cefuroxime randomly for 4 or 7 days. Besides blood and throat cultures, the etiology was searched by serology for 23 different agents. RESULTS: Of 154 children analyzed, a probable etiology was established in 96. Of those, a bacterial infection, with or without concomitant viral infection, was disclosed in 80% and 94% in the 4-day and 7-day treatment groups, respectively; pneumococcus being the commonest agent. There was one possible treatment failure in the 4-day group, but with a questionable relation to the short course. Three patients in the 4-day and two in the 7-day group underwent treatment changes, or were rehospitalized within 30 days. All children recovered entirely. CONCLUSIONS: Shortening parenteral beta-lactam treatment to 4 days in infections for which most parenteral antimicrobials are instituted, is not only safe, but reduces costs, is ecologically sound, and minimizes the risks of nosocomial infections and other adverse effects of treatment.

Antimicrobial treatment of an experimental otitis media caused by a beta-lactamase positive isolate of Haemophilus influenzae.

A gerbil model of otitis media induced by a beta-lactamase producing and non-serotypeable isolate of Haemophilus influenzae was used to assess the in-vivo efficacy of co-amoxiclav and cefuroxime at low (5 mg/kg) and high (20 mg/kg) doses. The MIC of the antibiotics tested against the pathogen was 1 mg/L (1/0.5 mg/L for co-amoxiclav). The organism was inoculated (+/-10(6) cfu) by transbullar challenge directly in the middle ear and antibiotic treatment was commenced 2 h post-inoculation and continued at 8 h intervals for three doses. Only high dose co-amoxiclav significantly reduced the number of culture-positive specimens as compared with untreated animals or with other treatment groups (91.7% as compared with 36.7% for high dose cefuroxime). The results obtained in any treatment group were related to middle ear antibiotic level/MIC. Antibiotic concentrations in the middle ear 90 min after administration were about 10% of serum levels at 15 min, probably related to a slight inflammatory response. Only after high dose co-amoxiclav did the concentration in the middle ear exceed the MIC by a factor of four. In otitis media with effusion, if indicated, antibiotics active in vitro should be administered in high doses and, to avoid side effects, probably in short courses.

Clinical effectiveness of levofloxacin in patients with acute purulent exacerbations of chronic bronchitis: the relationship with in-vitro activity.

The objective of this randomized, double-blind study was to compare the clinical efficacy of levofloxacin at two different dosages with that of cefuroxime axetil in patients with acute purulent exacerbations of chronic bronchitis and, in particular, to assess the impact of the susceptibility to levofloxacin on the clinical findings. In total, 124 evaluable patients were treated for 7 days with oral levofloxacin 250 mg or 500 mg od, or cefuroxime axetil 250 mg bd. Sputum cultures were monitored pre-treatment, and at 1 and 7 days after the end of treatment. The susceptibility of Streptococcus pneumoniae isolates was tested by agar dilution in Columbia blood agar and by disc diffusion, but all other isolates were tested solely by the disc diffusion method. A greater number of infections were eradicated by levofloxacin than by cefuroxime axetil: infections were eradicated in 68% of patients receiving the 500 mg dosage and in 63% of those taking 250 mg levofloxacin, whereas the eradication rate with the comparator drug was much lower (48%). Against all pre-treatment S. pneumoniae isolates (n = 39), the MICs of levofloxacin were between 0.25 and 2 mg/L (geometric mean 0.95 mg/L), similar to those of the post-treatment strains (n = 32; mean 1.11 mg/L). All except one of the S. pneumoniae isolates were susceptible to penicillin G (MIC < or = 0.06 mg/L), and the remaining isolate was inhibited by 0.5 mg/L of penicillin G, but was fully susceptible to levofloxacin. Some pretreatment strains of Pseudomonas aeruginosa were resistant to levofloxacin, but many more resistant strains were encountered afterwards. All strains of Moraxella catarrhalis and Haemophilus influenzae were highly susceptible to levofloxacin in the disc diffusion tests. All the antimicrobial agents used in the study were well tolerated: only two patients discontinued treatment because of adverse drug effects. The results of this study indicated that, although there were some failures in patients with S. pneumoniae and P. aeruginosa infections, resistance to levofloxacin did not emerge rapidly among strains of S. pneumoniae during therapy with levofloxacin, and that natural resistance among pneumococci, H. influenzae and M. catarrhalis was rare.

Cefuroxime axetil. A review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy.

Cefuroxime axetil is an oral cephalosporin which is rapidly hydrolysed to the active parent compound, cefuroxime. Cefuroxime has a broad spectrum of in vitro antibacterial activity which encompasses methicillin-sensitive staphylococci and the common respiratory pathogens Streptococcus pneumoniae, Haemophilus influenzae, Moraxella (Branhamella) catarrhalis and group A beta-haemolytic streptococci. Cefuroxime has broad spectrum activity against the beta-lactamase positive respiratory pathogens H. influenzae and M. catarrhalis; it is also active against penicillin-susceptible and -intermediate strains of S. pneumoniae. In clinical trials, cefuroxime axetil (administered twice daily) has been evaluated in the treatment of upper and lower respiratory tract infections and has demonstrated similar efficacy to established antibacterial agents, including amoxicillin/clavulanic acid and cefaclor. Five days' treatment with cefuroxime axetil was recently shown to be as effective as 10 days' treatment with either cefuroxime axetil or amoxicillin/clavulanic acid in patients with acute otitis media or acute bronchitis. Cefuroxime axetil was at least as effective as phenoxymethylpenicillin (penicillin V) in the treatment of patients with group A beta-haemolytic streptococcal tonsillopharyngitis. A number of studies have evaluated the efficacy of cefuroxime axetil as the oral component of intravenous to oral sequential therapy in hospitalised patients with lower respiratory tract infection. In each study patients received parenteral cefuroxime for approximately 2 days followed by cefuroxime axetil for 5 to 10 days. In comparative studies, cefuroxime sequential therapy was as effective as amoxicillin/ clavulanic acid sequential therapy and full courses of parenteral cefuroxime, cefotiam or cefoperazone. Adults with urinary tract infections and skin infections were also effectively treated with cefuroxime axetil, as were adults and adolescents with early stage lyme disease. Cefuroxime axetil is associated with a low incidence of adverse events, with gastrointestinal disturbances being the most frequently observed. Thus, cefuroxime axetil is an effective and convenient treatment for a wide range of infections and may be considered a therapeutic option when empirical treatment of community-acquired infections is required. Moreover, given the promising results of several intravenous/oral sequential treatment studies, cefuroxime axetil may also become established as an oral component of sequential treatment regimens.

[Antibiotic prophylaxis using cefuroxime in bile duct endoscopy]. / Antibiotische Prophylaxe mit Cefuroxim bei endoskopischen Eingriffen an den Gallenwegen.

OBJECTIVE: To assess prospectively the effectiveness of a single prophylactic dose of cefuroxim before therapeutic endoscopy, in view of the general practice not to give antibiotics routinely. PATIENTS AND METHODS: In a prospective study endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography with drainage (PTCD) together with simultaneous stone extraction, dilatation or stent implantation were performed in 99 patients (51 men, 48 women; mean age 60.6 +/- 19.2 years). Group A (n = 49) received 1500 mg cefuroxim i.e. 30 min before the procedure, while none was given to group A patients (n = 50). Several blood cultures were taken up to 60 min after the endoscopy. The number of septicaemias (bacteraemia with fever, rigor, circulatory reactions, leukocytosis or leukopenia) were noted. Bile cultures were obtained in 56 patients with indwelling biliary drainage. RESULTS: Incidence of bacteraemia was 6.1% (3 of 49) in group A, 16% (8 of 50) in group B, but this difference is not statistically significant. The septicaemia rate was 6.1% in group A and 10% in group B (not significant). There were eleven positive blood cultures with 12 different microorganisms, Escherichia coli in four (A: n = 3). In vitro cefuroxim sensitivity was 53.3%. 25 different bacterial species were isolated from 73.2% of bile cultures, of which 53.4% were sensitive to cefuroxim and 8.2% moderately so. CONCLUSION: Although the obtained differences between the two groups were not statistically different, the reduction in bacteraemia/septicaemia rate may be of clinical use. Further studies are needed with higher dosages or antibiotic combinations to improve these results.

[The influence of selected antibiotics on the central action of aminophyllines--experimental studies]. / Wplyw wybranych antybiotyków na osrodkowe dzialanie aminofiliny--badania doswiadczalne.

Methylxanthines and some antibiotics can cause side effects, provoked by their central action, e.g. seizures. The epileptogenic effects of given drugs can be intensified during combined treatment, as a result of pharmacological interactions. In the present study the author investigated the influence of some commonly used antibiotics: benzylpenicillin, cefuroxime, doxycycline and amikacin upon central activity of methylxanthines in mice. The obtained results suggest, that all tested antibiotics, mainly benzylpenicillin, enhanced epileptogenicity of aminophylline in chemical seizures test. benzylpenicillin as only one among chosen antibiotics presented her own convulsant activity. During electrostimulation test, benzylpenicillin, doxycycline and amikacin intensified convulsions induced by methylxanthines. Only cefuroxime had no influence upon central action of methylxanthines in that experiments. Analysis of drugs' plasma levels, with using immunofluorescence methods, excluded pharmacokinetic interactions between them. Results of present investigation indicate, that there is a possibility of intensification of drugs' convulsant activity during combined treatment-aminophylline with some antibiotics in medical practice.

Evaluation of the E test for antimicrobial susceptibility testing of Porphyromonas gingivalis.

The antimicrobial susceptibilities of 81 recent clinical Porphyromonas gingivalis isolates and two reference strains were determined by the E test, a new method, and were compared with the minimal inhibitory concentrations for these strains obtained by the reference agar dilution method on supplemented Brucella blood agar. The following agreements were obtained: benzylpenicillin 100%, ampicillin 96%, cefaclor 82%, cefuroxime 91%, erythromycin 93%, clindamycin 99%, tetracycline 66%, doxycycline 89%, metronidazole 77% and ciprofloxacin 77%. Very major discrepancies were observed with ciprofloxacin. This study indicates that the E test is an acceptable method to determine the susceptibility of P. gingivalis for most antimicrobials.

In vitro antimicrobial susceptibility of different serotypes of Actinobacillus actinomycetemcomitans.

In vitro susceptibility of Actinobacillus actinomycetemcomitans (A.a.) serotypes to selected antimicrobial agents was investigated by the agar dilution method on supplemented Mueller-Hinton test medium. Eighty-three A.a. strains, 80 recent isolates from 40 periodontally healthy or diseased subjects, and three type strains were included in the study. Serotype a represented 20, serotype b 32, serotype c 17, and serotype e 7 and nontypable 4 of the tested strains. The most effective drugs against all A.a. serotypes in vitro were cefaclor, cefuroxime, tetracycline hydrochloride, doxycycline, trimethoprim-sulfamethoxazole (cotrimoxazole), and ciprofloxacin, which inhibited 100% of the strains at 4.0 micrograms/ml, 4.0 micrograms/ml, 1.0 microgram/ml, 2.0 micrograms/ml, 0.06 microgram/ml, and 0.015 microgram/ml, respectively. Serotypes a and e were more susceptible to cefaclor and cefuroxime than were serotypes b and c; 100% of the first two groups were inhibited at 2.0 micrograms/ml and 1.0 microgram/ml. Ampicillin inhibited 92% of the tested strains at 1.0 microgram/ml. Serotype b was always susceptible to ampicillin. Metronidazole exhibited the best activity against serotype a strains. The lowest minimal inhibitory concentration values for benzylpenicillin, ampicillin, erythromycin, doxycycline, and metronidazole were encountered among serotype b isolates. The results of the present study indicate minor differences in the in vitro antimicrobial susceptibility patterns of different A.a. serotypes, except to metronidazole. Also, the new oral cephalosporins and cotrimoxazole, rare antimicrobial agents in periodontology, showed promising efficacy against all A.a. strains.