Application of cefuroxime in the eradication therapy of Helicobacter pylori infection: A review article.

BACKGROUND: Helicobacter pylori infection and its associated diseases represent a significant global health concern. Patients who cannot use amoxicillin pose a therapeutic challenge and necessitate alternative medications. Preliminary research indicates that cefuroxime demonstrates promising potential for eradicating H. pylori infection, and there is a lack of comprehensive review articles on the use of cefuroxime. MATERIALS AND METHODS: This study conducts a thorough systematic literature review and synthesis. A comprehensive systematic search was conducted in PubMed, Web of Science, EMBASE, China National Knowledge Infrastructure, China Biology Medicine disc, and Wanfang Data up to January 13, 2024. The search strategy utilized the following keywords: (Cefuroxime) AND (Helicobacter pylori OR Helicobacter nemestrinae OR Campylobacter pylori OR Campylobacter pylori subsp. pylori OR Campylobacter pyloridis OR H. pylori OR Hp) for both English and Chinese language publications. Sixteen studies from five different countries or regions were included in final literature review. RESULTS: Analysis results indicate that H. pylori is sensitive to cefuroxime, with resistance rates similar to amoxicillin being relatively low. Regimens containing cefuroxime have shown favorable eradication rates, which were comparable to those of the regimens containing amoxicillin. Regarding safety, the incidence of adverse reactions in cefuroxime-containing eradication regimens was comparable to that of amoxicillin-containing regimens or other bismuth quadruple regimens, with no significant increase in allergic reactions in penicillin-allergic patients. Regarding compliance, studies consistently report high compliance rates for regimens containing cefuroxime. CONCLUSION: Cefuroxime can serve as an alternative to amoxicillin for the patients allergic to penicillin with satisfactory efficacies, safety, and compliance.

Comparative effectiveness of ß-lactams for empirical treatment of methicillin-susceptible Staphylococcus aureus bacteraemia: a prospective cohort study.

OBJECTIVES: Standard once-daily dosing of ceftriaxone may not lead to adequate antibiotic exposure in all cases of Staphylococcus aureus bacteraemia (SAB). Therefore, we compared clinical effectiveness of empirical antibiotic treatment with flucloxacillin, cefuroxime and ceftriaxone in adult patients with MSSA bacteraemia. METHODS: We analysed data from the Improved Diagnostic Strategies in Staphylococcus aureus bacteraemia (IDISA) study, a multicentre prospective cohort study of adult patients with MSSA bacteraemia. Duration of bacteraemia and 30 day SAB-related mortality were compared between the three groups using multivariable mixed-effects Cox regression analyses. RESULTS: In total, 268 patients with MSSA bacteraemia were included in the analyses. Median duration of empirical antibiotic therapy was 3 (IQR 2-3) days in the total study population. Median duration of bacteraemia was 1.0 (IQR 1.0-3.0) day in the flucloxacillin, cefuroxime and ceftriaxone groups. In multivariable analyses, neither ceftriaxone nor cefuroxime was associated with increased duration of bacteraemia compared with flucloxacillin (HR 1.08, 95% CI 0.73-1.60 and HR 1.22, 95% CI 0.88-1.71). In multivariable analysis, neither cefuroxime nor ceftriaxone was associated with higher 30 day SAB-related mortality compared with flucloxacillin [subdistribution HR (sHR) 1.37, 95% CI 0.42-4.52 and sHR 1.93, 95% CI 0.67-5.60]. CONCLUSIONS: In this study, we could not demonstrate a difference in duration of bacteraemia and 30 day SAB-related mortality between patients with SAB empirically treated with flucloxacillin, cefuroxime or ceftriaxone. Since sample size was limited, it is possible the study was underpowered to find a clinically relevant effect.

New regimens as first-line eradication therapy for Helicobacter pylori infection in patients allergic to penicillin: A randomized controlled trial.

BACKGROUND: Helicobacter pylori eradication in penicillin-allergic patients is challenging. The effective regimen is lacking in areas with high antibiotic resistance and tetracycline unavailable. Minocycline, cefuroxime, and full-dose metronidazole are promising drugs. AIMS: To compare the eradication rate, safety, and compliance among three new bismuth quadruple therapies for first-line H. pylori eradication in penicillin-allergic patients. METHODS: This randomized trial was conducted on 450 naive patients with H. pylori infection and penicillin allergy. The 14-day minocycline-metronidazole-containing (minocycline 100 mg twice daily and metronidazole 400 mg four times/day), minocycline-cefuroxime-containing (minocycline 100 mg twice daily and cefuroxime 500 mg twice daily), and cefuroxime-metronidazole-containing (cefuroxime 500 mg twice daily and metronidazole 400 mg four times/day) bismuth quadruple therapies were randomly assigned to the participants. Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed 4-8 weeks after eradication to evaluate outcome. RESULTS: The differences of eradication rates in either intention-to-treat (84.0%, 82.7%, and 23 82.0%, p = .896) or per-protocol (91.7%, 90.9%, and 88.2%, p = .599) analysis among minocycline-metronidazole, minocycline-cefuroxime, and cefuroxime-metronidazole-containing bismuth quadruple therapies were statistically insignificant. The incidence of adverse events (35.1%, 22.6%, and 28.9%) and compliance (90.5%, 91.8%, and 91.9%) were similar. Taste distortion, nausea, and anorexia were more common in metronidazole-containing regimens, and dizziness was more common in minocycline-containing regimens. The allergy was rare (~3%). CONCLUSIONS: The efficacies of three bismuth quadruple therapies containing minocycline, cefuroxime, and full-dose metronidazole (pairwise) for first-line H. pylori eradication in penicillin-allergic patients were similarly satisfactory with relatively good safety and compliance. The study was registered in the Chinese Clinical Trials Registration (ChiCTR1900023702).

Multi-drug resistant Klebsiella-induced corneal ulcer following pterygium surgery: a case report.

BACKGROUND: Management of pterygium is dependent on the grading of pterygium and its clinical presentation (inflamed or quiescent), and surgical excision is the final choice of treatment for the pterygium extending beyond the limbus. Infectious keratitis is one of the most commonly reported complications in recent years. To the best of our knowledge, Klebsiella keratitis after pterygium surgery has not been described in the current literature. Here, we report a patient with corneal ulcer formation following pterygium surgical excision. CASE PRESENTATION: A 62-year-old woman presented with complaints of pain, blurred vision, photophobia and redness in her left eye for a month. She had a history of pterygium surgical excision two months ago. Slit-lamp examination showed conjunctival congestion, a central whitish corneal ulcer with a central epithelial defect, and hypopyon. Corneal scraped sample revealed multidrug resistant (MDR) Klebsiella pneumonia and the strain was found to be sensitive to cefoxitin and ciprofloxacin. Intracameral cefuroxime (1 mg/0.1 mL) injection, fortified cefuroxime ophthalmic suspension (50 mg/mL) and moxifloxacin ophthalmic suspension (0.5%) were successfully administered to control the infection. Since residual central stromal opacification remained persistent, final visual acuity did not improve beyond finger counting at two meters. CONCLUSIONS: Klebsiella keratitis is a rare and sight-threatening complication following pterygium excision. This report emphasizes the importance of close follow-up examination following pterygium surgeries.

Effect of cefuroxime intracameral injection antibiotic prophylactic on postoperative endophthalmitis wound post-cataract: A meta-analysis.

To assess the impact of cefuroxime injection of intracameral prophylaxis antibiotic on after endophthalmitis operative wound following surgery of cataract, we conducted a meta-analysis. A thorough review of the literature up to July 2022 revealed that there were 1 167 197 participants with surgery of cataract at the start of the research; 1 004 425 of these subjects received an injection of intracameral of cefuroxime, while 162 772 did not get an antibiotic as a control. Using dichotomous approaches and a random or fixed-effect model, odds ratios (OR) with 95% confidence intervals (CIs) were estimated to evaluate the impact of cefuroxime injection of intracameral prophylaxis antibiotic on after endophthalmitis operative wound following surgery of cataract. When comparing no antibiotic in participants who had surgery of cataract, the cefuroxime injection of intracameral significantly reduced the after endophthalmitis operative wound (OR, 0.14; 95% CI, 0.07-0.29, P = 0.001) with high heterogeneity (I2 = 95%). When comparing participants who received no antibiotic after surgery of cataract, the after endophthalmitis operative wound from the cefuroxime injection of intracameral was considerably lower. Although none of the 22 studies encompassed in the meta-analysis had a study with a small sample size, it is nevertheless advisable to proceed with caution when analysing the results.

BACTERIAL PROFILE, ANTIMICROBIAL RESISTANCE, AND FACTORS ASSOCIATED WITH URINARY TRACT INFECTION AMONG PREGNANT WOMEN AT HOSANNA TOWN HEALTH FACILITIES, CENTRAL ETHIOPIA.

Urinary tract infection in pregnancy is a common microbial infection. Antimicrobial resistance among uropathogens is becoming a major health problem worldwide. The antimicrobial agents used to manage urinary tract infections during pregnancy should be carefully chosen. Therefore, this study aimed to determine the bacterial profile, antibiotic susceptibility pattern, and factors associated with urinary tract infection among pregnant women at Hosanna town public health facilities. A facility-based cross-sectional study was conducted from March to August 2022 on a total of 312 pregnant women who attended antenatal care at Hosanna Town public health facilities. Sociodemographic, clinical data, and related information were collected by using a pre-tested questionnaire. In addition, mid-stream urine specimens were collected from study participants. Bacterial pathogens were identified by standard bacteriological techniques. Antibiotic susceptibility testing was performed by using the Kirby Bauer disk diffusion method. The data were analyzed by using SPSS version 25. Chi-square and odds ratios were calculated and a P-value≤0.05 at a 95% confidence interval was considered statistically significant. The results were presented with words and tables. Of a total of pregnant women, 59/312(18.9%) (95% CI: 14.7-23.7) were found to have significant bacteriuria. The predominant isolates were Escherichia coli (E. coli) 22(34.4%), followed by coagulase-negative staphylococci (CoNS) 10(15.6%), Staphylococci aureus (S. aureus) 7(10.9%), and Klebsiella pneumoniae (K. pneumoniae) 6(9.4%). Overall, 78.1% of these isolates were multidrug-resistant (MDR). Gram-negative bacteria were susceptible to meropenem (97.6%), gentamicin (85.7%), nitrofurantoin (82.1%), ciprofloxacin (73.8%), amoxicillin-clavulanic acid (73.8%) and ceftriaxone (71.8%), but highly resistant to ampicillin (95.5%), trimethoprim-sulfamethoxazole (74.4%), doxycycline (71.8%), cefuroxime (69.2%), and cephalexin (69.2%). The gram-positive bacteria were susceptible to gentamicin (86.4%), erythromycin (81.8%), and nitrofurantoin (77.3%): whereas they showed a high level of resistance to penicillin (72.7%), doxycycline (54.5%), trimethoprim-sulfamethoxazole (52.9%), and cefoxitin (52.9%). No formal education for the participant (AOR: 2.86, 95% CI: 1.03-7.98, p=0.044), family monthly income <1500 birr (AOR: 3.19, 95% CI: 1.48-6.89, p=0.003), and previous history of UTI (AOR: 4.52, 95% CI: 2.04-10.03, p=0.001) were significantly associated with bacteriuria. This study revealed a high prevalence of bacterial urinary tract infection among pregnant women and low susceptibility to ampicillin, trimethoprim-sulfamethoxazole, cefuroxime, and cephalexin. Therefore, regularly, culture-based bacterial identification and antibiotic susceptibility testing should be performed. Alternatively, empiric antibiotic therapy should consider the prevalence of antibiotic-resistant uropathogens and the factor that may increase the urinary tract infection occurrence due to multi-drug resistant uropathogens.

Estimating the impact of cefuroxime versus cefazolin and amoxicillin/clavulanate use on future collateral resistance: a retrospective comparison.

BACKGROUND: Quantitative estimates of collateral resistance induced by antibiotic use are scarce. OBJECTIVES: To estimate the effects of treatment with amoxicillin/clavulanate or cefazolin, compared with cefuroxime, on future resistance to ceftazidime among hospitalized patients. METHODS: A retrospective analysis of patients with positive bacterial cultures hospitalized in an Israeli hospital during 2016-19 was conducted. Patients were restricted to those treated with amoxicillin/clavulanate, cefazolin or cefuroxime and re-hospitalized with a positive bacterial culture during the following year. Matching was performed using exact, Mahalanobis and propensity score matching. Each patient in the amoxicillin/clavulanate and cefazolin groups was matched to a single patient from the cefuroxime group, yielding 185:185 and 298:298 matched patients. Logistic regression and the g-formula (standardization) were used to estimate the OR, risk difference (RD) and number needed to harm (NNH). RESULTS: Cefuroxime induced significantly higher resistance to ceftazidime than amoxicillin/clavulanate or cefazolin; the marginal OR was 1.76 (95% CI = 1.16-2.83) compared with amoxicillin/clavulanate and 1.98 (95% CI = 1.41-2.8) compared with cefazolin and the RD was 0.118 (95% CI = 0.031-0.215) compared with amoxicillin/clavulanate and 0.131 (95% CI = 0.058-0.197) compared with cefazolin. We also estimated the NNH; replacing amoxicillin/clavulanate or cefazolin with cefuroxime would yield ceftazidime resistance in 1 more patient for every 8.5 (95% CI = 4.66-32.14) or 7.6 (95% CI = 5.1-17.3) patients re-hospitalized in the following year, respectively. CONCLUSIONS: Our results indicate that treatment with amoxicillin/clavulanate or cefazolin is preferable to cefuroxime, in terms of future collateral resistance. The results presented here are a first step towards quantitative estimations of the ecological damage caused by different antibiotics.

Clinical and microbiological characterization of Aerococcus urinae bacteraemias at Helsinki metropolitan area, Finland.

Our objective was to assess the incidence of bacteraemic Aerococcus urinae cases at Helsinki metropolitan area, Finland, from a 6-year study period (2013 to 2018) and to further characterize available cases. The study evaluates the outcome of commonly used cefuroxime treatment and determinate a set of A. urinae in vitro antimicrobial susceptibilities for benzylpenicillin, cefuroxime, and ceftriaxone. Clinical records of A. urinae bacteraemic patients were reviewed retrospectively. Antimicrobial susceptibility testing was performed by disk diffusion, gradient test, and broth microdilution for 139-141 clinical A. urinae isolates. Clinical data of 72/77 patients were combined with the in vitro susceptibilities. We found an increasing number of bacteraemic A. urinae cases within 6-year study period (p = 0.01). The patients were mainly elderly males, and all suffered from underlying conditions. A total of 27.3% of cases (21/77) showed polymicrobial blood cultures. Thirty-day mortality was 22.1%. Cefuroxime was the initial empiric antimicrobial agent given for 66/76 of the patients and treatment outcome was favorable for 20/22 patients who received cefuroxime at least up to day 5. All isolates were susceptible to benzylpenicillin and cefuroxime interpreted by EUCAST breakpoints for Aerococci and PK-PD breakpoints, respectively. MIC determinations gave variable results for ceftriaxone, 2.1-2.9% of the isolates were resistant. To conclude, it seems that the number of bacteraemic Aerococcus urinae cases is increasing at Helsinki metropolitan area, Finland, reflecting the growing blood culture sampling. Clinical A. urinae isolates were susceptible to cefuroxime in vitro. Treatment data indicate that empirical cefuroxime started for possibly urinary tract -derived community-acquired bacteraemia covers A. urinae.

Adjunctive azithromycin prophylaxis protects women from uterine cesarean scar defect: A randomized controlled trial.

INTRODUCTION: Cesarean scar defect (CSD) is a long-term outcome of cesarean section (CS) and associated with numerous gynecological and obstetric problems. Previous studies indicate that infection may be a risk factor for CSD. Adjunctive azithromycin was shown to reduce the risk of postoperative infection in patients undergoing non-elective primary cesarean delivery in labor or after the rupture of membranes compared with standard antibiotic prophylaxis. This study investigated the protective effect of adjunctive azithromycin in combination with single-dose cephalosporin against CSD in women undergoing non-elective cesarean delivery. MATERIAL AND METHODS: A randomized, double-blind, controlled clinical trial was conducted in a University hospital in Shanghai, China. A total of 242 women who underwent their first non-elective CS were randomly assigned to receive 1500 mg cefuroxime sodium plus 500 mg intravenous azithromycin (n = 121; experimental group) or 1500 mg cefuroxime sodium plus a placebo (n = 121; placebo group). The primary outcome was CSD prevalence, as determined by transvaginal ultrasound and saline infusion sonohysterography within 6 months of delivery. Secondary outcomes were changes in infectious indicators (eg hypersensitive C-reactive protein and procalcitonin), postoperative morbidity, and use of postoperative antibiotics. We also examined the operative procedure, pathogenic microorganism cultures, and fetal outcomes. Outcomes were compared between groups with the chi-squared test, Fisher's exact test, or Student's t test. RESULTS: Between May 2018 and May 2021, 121 women were randomized to each arm. Because the sonographic follow up was disrupted by the coronavirus disease 2019 pandemic and strict management policies, we merged the follow-up time points (6 weeks and 6 months) into a single time period (6 weeks to 6 months); 104 and 108 women in the experimental and placebo groups, respectively, completed the first sonographic follow up. CSD was diagnosed by sonography in 34/104 (32.7%) and 50/108 (46.3%) patients in the experimental and placebo groups, respectively (relative risk 0.71, 95% confidence interval 0.50-0.99; p = 0.043). Characteristics of CSD and short-term infection outcomes did not differ between groups. CONCLUSIONS: A single dose of intravenous 500 mg azithromycin adjunctive to single-dose cefuroxime prophylaxis significantly reduced the incidence of CSD in women undergoing non-elective CS.

Clinical features and recurrence of Corynebacterium kroppenstedtii infection in patients with mastitis.

BACKGROUND: Few studies have investigated the differences in clinical features of patients with mastitis following Corynebacterium kroppenstedtii infection, and most focused on the bacterial antimicrobial susceptibility, detection methods and therapy. METHODOLOGY: There were 133 patients with mastitis infected by C. kroppenstedtii between August 2016 and September 2019. C. kroppenstedtii was identified using mass spectrometry. The demographics, clinical diagnosis, laboratory test results of different types of mastitis combined with bacillus infection, and the effects of different treatments in reducing recurrence were compared. RESULTS: The incidence of pus following C. kroppenstedtii infection was higher in patients with non-granulomatous lobular mastitis (NGLM; 56.6%) than in those with granulomatous lobular mastitis (GLM; 33.3%; χ2 = 7.072, p = 0.008). While C-reactive protein (CRP) was higher in the GLM group (12.50 mg/L) than in the NGLM group (6.05 mg/L; Z = - 2.187, p = 0.029). Treatment with local lavage (triamcinolone acetonide) and antibiotics (cefuroxime) showed a recurrent rate of 25.9% in C. kroppenstedtii infection. CONCLUSION: Increased pus, large masses, and an elevated CRP level may occur in patients with mastitis infected by C.kroppenstedtii. These clinical features may guide the determination of the bacterial infection in patients with mastitis. Combining an antibiotic with a triamcinolone acetonide lavage, preferably cefuroxime, may reduce the recurrence.

Population pharmacokinetic evaluation of cefuroxime in perioperative antibiotic prophylaxis during and after cardiopulmonary bypass.

AIMS: The purpose of this study was to explore pharmacokinetic and pharmacodynamic aspects of a contemporary dosing scheme of cefuroxime as perioperative prophylaxis in cardiac surgery using cardiopulmonary bypass (CPB). METHODS: Cefuroxime plasma concentrations were measured in 23 patients. A 1.5-g dose of cefuroxime was administered at start of surgery and CPB, followed by 3 additional doses every 6 hours postoperative. Drug levels were used to build a population pharmacokinetic model. Target attainment for Staphylococcus aureus (2-8 mg/L) and Escherichia coli (8-32 mg/L) were evaluated and dosing strategies for optimization were investigated. RESULTS: A dosing scheme of 1.5 g cefuroxime preoperatively with a repetition at start of CPB achieves plasma unbound concentrations of 8 mg/L in almost all patients during surgery. The second administration is critical to provide this level of coverage. Simulations indicate that higher unbound concentrations up to 32 mg/L are reached by a continuous infusion rate of 1 g/h after a bolus of 1 g. In the postoperative phase, most patients do not reach unbound concentrations above 2 mg/L. To improve target attainment up to 8 mg/L, the continuous application of cefuroxime with infusion rates of 0.125-0.25 g/h is simulated and shown to be an alternative to bolus dosing. CONCLUSION: Dosing recommendations for cefuroxime as perioperative antibiotic prophylaxis in cardiac surgery are sufficient to reach plasma unbound concentration to cover S. aureus during the operation. Target attainment is not achieved in the postoperative period. Continuous infusion of cefuroxime may optimize target attainment.

Mode of bacterial killing affects the inflammatory response and associated organ dysfunctions in a porcine E. coli intensive care sepsis model.

BACKGROUND: Sepsis is often treated with penicillin-binding protein 3 (PBP-3) acting ß-lactam antibiotics, such as piperacillin-tazobactam, cefotaxime, and meropenem. They cause considerable bacterial structural changes and have in vitro been associated with an increased inflammatory response. In a clinically relevant large animal sepsis model, our primary aim was to investigate whether bacteria killed by a PBP-3-active antibiotic has a greater effect on the early inflammatory response and organ dysfunction compared with corresponding amounts of live or heat-killed bacteria. A secondary aim was to determine whether the addition of an aminoglycoside could mitigate the cefuroxime-induced response. METHOD: Killed or live Escherichia coli were administrated as a 3-h infusion to 16 healthy pigs in a prospective, randomized controlled interventional experimental study. Cefuroxime was chosen as the PBP-3-active antibiotic and tobramycin represented the aminoglycosides. The animals were randomized to receive (I) bacteria killed by cefuroxime, (II) live bacteria, (III) bacteria killed by heat, or (IV) bacteria killed by the combination of cefuroxime and tobramycin. Plasma endotoxin, tumor necrosis factor alpha, interleukin-6, interleukin-10, leukocytes, and organ function were recorded at the start of the experiment and then hourly for 6 h. RESULTS: Differences in dynamics of concentration over time between the four treatment groups were found for the three cytokines (p < 0.001). Animals receiving cefuroxime-killed bacteria demonstrated higher responses than those receiving live (p < 0.05) or heat-killed bacteria (p < 0.01). The addition of tobramycin reduced the cefuroxime-induced responses (p < 0.001). The cytokine responses were associated with leucocyte activation that was further associated with pulmonary dysfunction and increases in lactate (p < 0.01). CONCLUSIONS: In comparison with live or heat-killed bacteria, bacteria killed by a PBP-3-active antibiotic induced an increased inflammatory response that appears to be associated with deteriorated organ and cellular function. The addition of an aminoglycoside to the PBP-3-active antibiotic reduced that response.

Preoperative antibiotic prophylaxis regimen in brain tumour surgery in Sweden: a quasi-experimental study.

BACKGROUND: There has been varied clinical practice concerning antibiotic prophylaxis in patients undergoing craniotomy. In Sweden, both Cloxacillin and Cefuroxime have frequently been used. We aimed to study the clinical effectiveness of these two regimens. METHODS: A quasi-experimental design was used. The sample consisted of 580 adult (> 18 years) patients operated 2012-2015, of which 375 received Cloxacillin (pre-intervention group) and 205 received Cefuroxime (intervention group). Primary endpoint was the incidence of surgical site infection (SSI) 12 months after surgery, while secondary endpoints were the need for reoperation due to SSI, the amount antibiotics used and the number of visits in the outpatient clinic related to SSI. A control group from another institution was reviewed to rule out clinical trial effects. RESULTS: When analysed by intention to treat, the pre-intervention group had a significant higher incidence of SSI, 13.3% (50/375) vs 5.4% (11/205) in the intervention group (p < 0.01). A treatment per protocol analysis confirmed the result. The number of reoperations due to SSI were significantly reduced in the intervention group, 3.4% (7/205) vs 8.3% (31/375) (p = 0.02), as was the total antibiotic use (p = 0.03) and the number of visits in the outpatient clinic (p < 0.01). In the control group, the reoperation rate as result of SSI was lower (p = 0.02) prior to the opposite change from Cefuroxime to Cloxacillin, 1.8% (27/1529) vs 3.1% (43/1378). CONCLUSION: In Sweden, Cefuroxime as prophylaxis in brain tumour surgery by craniotomy seems to be superior to Cloxacillin.

Physiologically based pharmacokinetic evaluation of cefuroxime in perioperative antibiotic prophylaxis.

AIMS: Adequate plasma concentrations of antibiotics during surgery are essential for the prevention of surgical site infections. We examined the pharmacokinetics of 1.5 g cefuroxime administered during induction of anaesthesia with follow-up doses every 2.5 hours until the end of surgery. We built a physiologically based pharmacokinetic model with the aim to ensure adequate antibiotic plasma concentrations in a heterogeneous population. METHODS: A physiologically based pharmacokinetic model (PK-Sim® /MoBi® ) was developed to investigate unbound plasma concentrations of cefuroxime. Blood samples from 25 thoracic surgical patients were analysed with high-performance liquid chromatography. To evaluate optimized dosing regimens, physiologically based pharmacokinetic model simulations were conducted. RESULTS: Dosing simulations revealed that a standard dosing regimen of 1.5 g every 2.5 hours reached the pharmacokinetic/pharmacodynamic target for Staphylococcus aureus. However, for Escherichia coli, >50% of the study participants did not reach predefined targets. Effectiveness of cefuroxime against E. coli can be improved by administering a 1.5 g bolus immediately followed by a continuous infusion of 3 g cefuroxime over 3 hours. CONCLUSION: The use of cefuroxime for perioperative antibiotic prophylaxis to prevent staphylococcal surgical site infections appears to be effective with standard dosing of 1.5 g preoperatively and follow-up doses every 2.5 hours. In contrast, if E. coli is relevant in surgeries, this dosing regimen appears insufficient. With our derived dose recommendations, we provide a solution for this issue.

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 .

The Influence of National Guidelines on the Management of Community-Acquired Pneumonia in Children. Do Pediatricians Follow the Recommendations?

This is a retrospective study whose main objective was to analyze the influence of the Polish Guidelines for the Management of Respiratory Tract Infections of 2010 (PGMRTI) on in-hospital treatment of children with community-acquired pneumonia (CAP). Files from four Warsaw hospitals were reviewed to identify children with uncomplicated CAP, treated before (2008-2009) (pre-PGMRTI) and after (2011-2012) (post-PGMRTI) publication of the guidelines. Predefined data on the management were compared. A cohort of 2,359 children (1,081 pre-PGMRTI and 1,278 post-PGMRTI) was included. We found that co-amoxiclav was the most common first-line therapy in children >3 months of age (34.6% and 40.4% pre- and post-PGMRTI, respectively), followed by cefuroxime (31.8% and 20.9% pre- and post-PGMRTI, respectively; p < 0.0001) and macrolides (17.4% and 24.5% pre- and post-PGMRTI, respectively; p < 0.0001). Amoxicillin was rarely used (5.4% and 4.9%, pre- and post-PGMRTI, respectively). The study revealed an overuse of inhaled bronchodilators, corticosteroids, and mucoactive drugs. Blood diagnostic tests were applied to a significant percentage of patients: blood cultures (41.2% and 44.5% pre-and post-PGMRTI, respectively) and serology for atypical pathogens (27.9% and 44.9% pre-and post-PGMRTI, respectively; p < 0.0001). The number of follow-up chest X-rays increased (30.5% and 53.8% pre- and post-PGMRTI, respectively; p < 0.0001). In conclusion, the study demonstrates an unsatisfactory influence of the guidelines on in-hospital management of CAP in children. Despite an explicit recommendation for the use of amoxicillin, it was still underused. Other methods of education and guideline dissemination are needed to optimize the prescribing of antibiotics.

Hydration of small leaking corneal perforations with cefuroxime.

PURPOSE: To describe a new technique for sealing small corneal perforations after penetrating trauma. METHODS: Corneal perforations in six eyes were sealed using a stromal cefuroxime hydration technique. This technique is identical to the current method used to seal leaking incisions upon completion of cataract surgery except for the use of cefuroxime instead of balanced salt solution. Additionally, cefuroxime was intentionally injected into the anterior chamber. A therapeutic contact lens was used after the hydration. Comparison was made in eight eyes with small traumatic corneal perforation that was sealed using therapeutic contact lenses without hydration. RESULTS: This novel technique was applied in six cases, with leakage stopping immediately following hydration in each of these eyes. In cases presenting with a shallow or flat anterior chamber, this maneuver produced immediate reformation of the chamber. Of note, the corneal scars after hydration were minimal with little effect on visual acuity. When compared to eyes with small corneal perforations which were sealed with therapeutic contact lenses without hydration, all cases that were hydrated with cefuroxime were sealed immediately, as opposed to cases treated without hydration. Furthermore, the eyes that underwent hydration with cefuroxime had a worse average visual acuity on admission, a better average visual acuity 1 month post-trauma, and a shorter average length of hospitalization. CONCLUSIONS: This new technique offers five major advantages: (1) Immediate sealing of the corneal perforation is achieved. (2) Definitive treatment can be achieved at the slit lamp. (3) Since neither stitches nor glue is applied, healing is achieved with minimal scarring and discomfort. (4) Little equipment is required. (5) Injection of cefuroxime into the anterior chamber provides prophylaxis against infection.

Population Pharmacokinetic Model-Based Evaluation of Standard Dosing Regimens for Cefuroxime Used in Coronary Artery Bypass Graft Surgery with Cardiopulmonary Bypass.

The purpose of this study was to investigate the population pharmacokinetics (PK) of cefuroxime in patients undergoing coronary artery bypass graft (CABG) surgery. In this observational pharmacokinetic study, multiple blood samples were collected over a 48-h interval of intravenous cefuroxime administration. The samples were analyzed by using a validated high-performance liquid chromatography (HPLC) method. Population pharmacokinetic models were developed using Monolix (version 4.4) software. Pharmacokinetic-pharmacodynamic (PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets. A total of 468 blood samples from 78 patients were analyzed. The PK for cefuroxime were best described by a two-compartment model with between-subject variability on clearance, the volume of distribution of the central compartment, and the volume of distribution of the peripheral compartment. The clearance of cefuroxime was related to creatinine clearance (CLCR). Dosing simulations showed that standard dosing regimens of 1.5 g could achieve the PK-PD target of the percentage of the time that the free concentration is maintained above the MIC during a dosing interval (fTMIC) of 65% for an MIC of 8 mg/liter in patients with a CLCR of 30, 60, or 90 ml/min, whereas this dosing regimen failed to achieve the PK-PD target in patients with a CLCR of ≥125 ml/min. In conclusion, administration of standard doses of 1.5 g three times daily provided adequate antibiotic prophylaxis in patients undergoing CABG surgery. Lower doses failed to achieve the PK-PD target. Patients with high CLCR values required either higher doses or shorter intervals of cefuroxime dosing. On the other hand, lower doses (1 g three times daily) produced adequate target attainment for patients with low CLCR values (≤30 ml/min).

Dynamics of Endotoxin, Inflammatory Variables, and Organ Dysfunction After Treatment With Antibiotics in an Escherichia coli Porcine Intensive Care Sepsis Model.

OBJECTIVES: To investigate the dynamics of antibiotic-induced endotoxin liberation and inflammatory response in vivo in a clinically relevant large animal intensive care sepsis model and whether the addition of an aminoglycoside to a ß-lactam antibiotic affects these responses. DESIGN: Prospective, placebo-controlled interventional experimental study. SETTING: University research unit. SUBJECTS: Thirty-six healthy pigs administered Escherichia coli as a 3-hour infusion. INTERVENTIONS: After 2 hours, during E. coli infusion, the animals were exposed to cefuroxime alone, the combination of cefuroxime and tobramycin, or saline. MEASUREMENTS AND MAIN RESULTS: Plasma endotoxin, interleukin-6, tumor necrosis factor-α, leucocytes, and organ dysfunction were recorded for 4 hours after antibiotic treatment, and differences to the values before treatment were calculated. In vitro experiments were performed to ascertain whether endotoxin is released during antibiotic-induced bacterial killing of this E. coli strain. Despite differences between the treatment arms in vitro, no differences in plasma endotoxin were observed in vivo. Antibiotic-treated animals demonstrated a higher interleukin-6 response (p < 0.001), greater leucocyte activation (p < 0.001), and more pronounced deterioration in pulmonary static compliance (p < 0.01) over time than controls. Animals treated with the combination showed a trend toward less inflammation. CONCLUSIONS: Treatment with antibiotics may elicit an increased inflammatory interleukin-6 response that is associated with leucocyte activation and pulmonary organ dysfunction. No observable differences were detected in plasma endotoxin concentrations. The reduction in cefuroxime-induced endotoxin release after the addition of an aminoglycoside in vitro could not be reproduced in this model.

Bacteramia Caused by Gardnerella Vaginalis in a Cesarean Section Patient.

BACKGROUND: Gardnerella vaginalis is a facultative anaerobic and small gram-variable rod bacterium. G. vaginalis, which can be transmitted through sexual contact, is the common pathogen for the feminine bacterial pathogen (BV). Here we describe a case of bacteremia in a patient after cesarean section caused by G. vaginalis in China. Case presentation: A 35-year-old woman suffered bacteremia caused by G. vaginalis after cesarean section. This patient, without evidence of polymicrobial infection, was treated with cefuroxime and had a good outcome. CONCLUSIONS: G. vaginalis bacteremia is rarely reported. Our report expands the range of infection caused by G. vaginalis.