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.

[Retrospective analysis of perioperative anaphylactic shock induced by cefuroxime].

This study investigated the characteristics and frequency of perioperative anaphylactic shock induced by cefuroxime, so as to provide a reference for the safe and rational use of cefuroxime in the perioperative period. Cases of perioperative anaphylactic shock caused by cefuroxime in our hospital from 2011 to 2021 were extracted from the Adverse Drug Reaction Monitoring System. Literature reporting adverse drug reactions (ADR) including cefuroxime-induced anaphylactic shock in perioperative settings was collected from the CNKI, VIP, Wanfang, PubMed, and Web of Science databases from their respective inception to May 2022. Statistical analysis was performed for all cases of cefuroxime-induced perioperative anaphylactic shock. A total of 31 patients were included [13 men (48.1%) and 14 women (51.9%)], most of whom were over 60 years old (n=16, 59.3%); 9 (29.0%) patients had a history of drug allergy; 5 (16.1%) patients had received skin tests, but with negative results; 28 (90.3%) patients received treatment intravenously; 22 (71.0%) patients were treated after anesthesia. For 20 (64.5%) patients the ADR occurred within 10 minutes after anesthesia. The main manifestations were hypotension, dyspnea, rash, and tachycardia. For all patients, symptoms resolved after withdrawal of the drug and active rescue, and there were no deaths. A history of allergy and skin test findings may have limitations in predicting perioperative anaphylactic shock caused by cefuroxime; greater vigilance should be exercised when using cefuroxime in the perioperative period. Close monitoring is recommended for patients undergoing treatment with cefuroxime. Rescue therapy should be administered for allergic shock, and suitable response measures must be taken in a timely manner to ensure the safety of patients.

Asymptomatic bacteriuria in patients with type 2 diabetes mellitus in rural southwestern Nigeria: a cross-sectional study.

OBJECTIVES: We aimed to identify the prevalence, bacterial isolates, antimicrobial susceptibility profile, and factors associated with asymptomatic bacteriuria (ASB) in patients with type 2 diabetes mellitus (T2DM) in rural southwestern Nigeria. METHODS: We performed a hospital-based cross-sectional study of patients with T2DM and ASB. Demographic and clinical data were collected using questionnaires. Urine samples were cultured using standard laboratory procedures, and bacterial colonies were isolated and antimicrobial sensitivity was performed using the disc diffusion technique. Relationships between variables were assessed using adjusted odds ratios (AORs) and 95% confidence intervals (CIs). RESULTS: Of the 280 participants, 73 (26.1%) had ASB (95% CI: 20.9%-31.2%). The most commonly identified isolate was E. coli (45/73; 61.7%), 100.0% of which were sensitive to cefuroxime but resistant to ciprofloxacin. Female sex (AOR, 6.132; 95% CI: 2.327-16.157), living below the poverty line (AOR, 2.066; 95% CI: 1.059-4.029), uncontrolled blood glucose (AOR, 2.097; 95% CI: 1.000-4.404), and a history of indwelling urethral catheterization (AOR, 14.521; 95% CI: 4.914-42.908) were associated with ASB. CONCLUSION: The findings suggest that cefuroxime should be used as an empirical treatment, pending urine culture and sensitivity, and that efforts should be made to prevent ASB in rural southwestern Nigeria.

Sensitizing methicillin-resistant Staphylococcus aureus (MRSA) to cefuroxime: the synergic effect of bicarbonate and the wall teichoic acid inhibitor ticlopidine.

Methicillin-resistant Staphylococcus aureus (MRSA) strains are a major challenge for clinicians due, in part, to their resistance to most ß-lactams, the first-line treatment for methicillin-susceptible S. aureus. A phenotype termed "NaHCO3-responsiveness" has been identified, wherein many clinical MRSA isolates are rendered susceptible to standard-of-care ß-lactams in the presence of physiologically relevant concentrations of NaHCO3, in vitro and ex vivo; moreover, such "NaHCO3-responsive" isolates can be effectively cleared by ß-lactams from target tissues in experimental infective endocarditis (IE). One mechanistic impact of NaHCO3 exposure on NaHCO3-responsive MRSA is to repress WTA synthesis. This NaHCO3 effect mimics the phenotype of tarO-deficient MRSA, including sensitization to the PBP2-targeting ß-lactam, cefuroxime (CFX). Herein, we further investigated the impacts of NaHCO3 exposure on CFX susceptibility in the presence and absence of a WTA synthesis inhibitor, ticlopidine (TCP), in a collection of clinical MRSA isolates from skin and soft tissue infections (SSTI) and bloodstream infections (BSI). NaHCO3 and/or TCP enhanced susceptibility to CFX in vitro, by both minimum inhibitor concentration (MIC) and time-kill assays, as well as in an ex vivo simulated endocarditis vegetations (SEV) model, in NaHCO3-responsive MRSA. Furthermore, in experimental IE (presumably in the presence of endogenous NaHCO3), pre-exposure to TCP prior to infection sensitized the NaHCO3-responsive MRSA strain (but not the non-responsive strain) to enhanced clearances by CFX in target tissues. These data support the notion that NaHCO3 is acting similarly to WTA synthesis inhibitors, and that such inhibitors have potential translational applications in the treatment of certain MRSA strains in conjunction with specific ß-lactam agents.

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.

Comparison of the effect between cefazolin/cefuroxime and broad-spectrum antibiotics in preventing post-operative pulmonary infections for smoking patients receiving video-assisted thoracoscopic lung surgery: a propensity score-matched retrospective cohort study.

BACKGROUND: The selection of prophylactic antibiotics for preventing post-operative pulmonary infections in smoking patients undergoing video-assisted thoracoscopic lung surgery (VATLS) is not clear. METHODS: In this retrospective cohort study, the outcomes of 572 smoking patients undergoing VATLS with prophylactic cefazolin/cefuroxime or other antibiotics were analyzed. Patients were classified as cefazolin/cefuroxime group and the control group. A 1:1 propensity score matching was also performed. RESULTS: The primary outcome of the incidence of post-operative pulmonary infection did not differ significantly between the two groups (23.7% vs 30.5%, RR = 0.777, 95%CI 0.564 ~ 1.070 p = 0.113). Similarly, secondary outcomes including the incidence of post-operative fever, the white blood cell count and neutrophils on the 3rd day after the surgery, and time for blood routine test recovery were all found without significant difference between the two groups. In the multivariate logistic regression model, no association was found between prophylactic use of cefazolin/cefuroxime and post-operative pulmonary infections after controlling other possible confounding factors (OR = 0.685, 95%CI 0.441 ~ 1.065, p = 0.093). CONCLUSIONS: Prophylactic use of cefazolin/cefuroxime was not associated with more adverse clinical outcomes among smoking populations undergoing VATLS when compared with broad-spectrum antibiotics and the two drugs are still feasible for peri-operative prophylactic use for smoking population before the surgery.

Dietary nobiletin regulated cefuroxime- and levofloxacin-associated "gut microbiota-metabolism" imbalance and intestinal barrier dysfunction in mice.

Nobiletin (NOB) exhibits significant biological activities and may be a potential dietary treatment for antibiotic-associated gut dysbiosis. In this study, mice were gavaged with 0.2 mL day-1 of 12.5 g L-1 cefuroxime (LFX) and 10 g L-1 levofloxacin (LVX) for a duration of 10 days, accompanied by 0.05% NOB to investigate the regulatory effect and potential mechanisms of NOB on antibiotic-induced intestinal microbiota disorder and intestinal barrier dysfunction. Our results indicated that dietary NOB improved the pathology of intestinal epithelial cells and the intestinal permeability by upregulating the expression of intestinal tight junction proteins (TJs) and the number of goblet cells. Furthermore, dietary NOB reduced the levels of serum lipopolysaccharide (LPS) and pro-inflammatory factors (TNF-α and IL-1ß), thereby facilitating the restoration of the intestinal mucosal barrier. Additionally, dietary NOB increased the abundance of beneficial bacteria f_Lachnospiraceae and regulated the metabolic disorders of short-chain fatty acids (SCFAs) and bile acids (BAs). Notably, NOB supplementation resulted in elevated levels of butyric acid and lithocholic acid (LCA), which contributed to the repair of the intestinal mucosal barrier function and the maintenance of intestinal homeostasis. Collectively, our results propose a healthy dietary strategy for the prevention or mitigation of antibiotic-associated gut dysbiosis by dietary NOB.

Broad-spectrum antibiotic prophylaxis in tumor and infected orthopedic surgery-the prospective-randomized, microbiologist-blinded, stratified, superiority trials: BAPTIST Trials.

BACKGROUND: The perioperative antibiotic prophylaxis with 1st or 2nd generation cephalosporins is evidence-based in orthopedic surgery. There are, however, situations with a high risk of prophylaxis-resistant surgical site infections (SSI). METHODS: We perform a superiority randomized controlled trial with a 10% margin and a power of 90% in favor of the broad-spectrum prophylaxis. We will randomize orthopedic interventions with a high risk for SSI due to selection of resistant pathogens (open fractures, surgery under therapeutic antibiotics, orthopedic tumor surgery, spine surgery with American Society of Anesthesiologists (ASA) score ≥ 3 points) in a prospective-alternating scheme (1:1, standard prophylaxis with cefuroxime versus a broad-spectrum prophylaxis of a combined single-shot of vancomycin 1 g and gentamicin 5 mg/kg parenterally). The primary outcome is "remission" at 6 weeks for most orthopedic surgeries or at 1 year for surgeries with implant. Secondary outcomes are the risk for prophylaxis-resistant SSI pathogens, revision surgery for any reason, change of antibiotic therapy during the treatment of infection, adverse events, and the postoperative healthcare-associated infections other than SSI within 6 weeks (e.g., urine infections or pneumonia). With event-free surgeries to 95% in the broad-spectrum versus 85% in the standard prophylaxis arm, we need 2 × 207 orthopedic surgeries. DISCUSSION: In selected patients with a high risk for infections due to selection of prophylaxis-resistant SSI, a broad-spectrum combination with vancomycin and gentamycin might prevent SSIs (and other postoperative infections) better than the prophylaxis with cefuroxime. TRIAL REGISTRATION: ClinicalTrial.gov NCT05502380. Registered on 12 August 2022. Protocol version: 2 (3 June 2022).

Assessment of Directional-Hemispherical Reflectance of Tablets with Cefuroxime during Storage under Elevated Temperature and Ultraviolet Radiation.

Environmental conditions can lead to changes in the physical and chemical structures of drug products. In this study, the stability of cefuroxime tablets stored under adverse conditions was evaluated based on total directional-hemispherical reflectance (THR). The THR value was measured before and after the tablets' exposure to stress factors (temperature of 45 °C and UV radiation). Each measurement was performed three times within seven spectral bands at the beginning of the experiment (day 0), and then on days 1, 2, 3, 5, and 7. In addition, hyperspectral profiles (400-1030 nm) were analyzed on days 0 and 7. A significant decrease in THR values in all wavelength ranges was observed when day 7 vs. day 0 were compared, especially for spectral bands of 335-380 nm and 1700-2500 nm (Δ = 0.220, p < 0.001 and Δ = 0.171, p < 0.001, respectively). The hyperspectral analysis confirmed a decrease in the reflectance after the end of stress conditions in the visible light range (400-700 nm) compared to tablets before the experiment. This may indicate that more radiation entered the tablets. In conclusion, the THR of cefuroxime tablets decreases during the exposure to heat and UV radiation, which may result from some physicochemical changes that have occurred during storage.

Development of a Generic Fetal Physiologically Based Pharmacokinetic Model and Prediction of Human Maternal and Fetal Organ Concentrations of Cefuroxime.

BACKGROUND AND OBJECTIVE: Physiologically based pharmacokinetic (PBPK) models for pregnant women have recently been successfully used to predict maternal and umbilical cord pharmacokinetics (PK). Because there is very limited opportunity for conducting clinical and PK investigations for fetal drug exposure, PBPK models may provide further insights. The objectives of this study were to extend a whole-body pregnancy PBPK model by multiple compartments representing fetal organs, and to predict the PK of cefuroxime in the maternal and fetal plasma, the amniotic fluid, and several fetal organs. METHODS: To this end, a previously developed pregnancy PBPK model for cefuroxime was updated using the open-source software Open Systems Pharmacology (PK-Sim®/MoBi®). Multiple compartments were implemented to represent fetal organs including brain, heart, liver, lungs, kidneys, the gastrointestinal tract (GI), muscles, and fat tissue, as well as another compartment lumping organs and tissues not explicitly represented. RESULTS: This novel PBPK model successfully predicted cefuroxime concentrations in maternal blood, umbilical cord, amniotic fluid, and several fetal organs including heart, liver, and lungs. Further model validation with additional clinical PK data is needed to build confidence in the model. CONCLUSIONS: Being developed with an open-source software, the presented generic model can be freely re-used and tailored to address specific questions at hand, e.g., to assist the design of clinical studies in the context of drug research or to predict fetal organ concentrations of chemicals in the context of fetal health risk assessment.

Second-Line Antibiotic Agents in Patient-Reported Penicillin or Cephalosporin Allergy Have No Negative Impact on Antibiotic Resistance After Hip and Knee Arthroplasty.

BACKGROUND: The aim of the present study was to compare causative bacteria and their antibiotic resistance profiles in patients developing a periprosthetic joint infection (PJI) based on preoperative prophylactic antibiotic regimens in primary total hip (THA) and primary total and unicompartmental knee arthroplasty (TKA/UKA). METHODS: We reviewed all cases of PJI occurring after primary THA and primary TKA/UKA, between 2011 and 2020 in a tertiary referral hospital. The standard preoperative prophylactic antibiotic for primary joint arthroplasty was cefuroxime and recommended second-line agent was clindamycin. Patients were divided by the replaced joint and analyzed independently. RESULTS: In the THA group, culture-positive PJI was detected in 61 of 3,123 (2.0%) cefuroxime-administered cases and 6 of 206 (2.9%) noncefuroxime-administered cases. In the TKA/UKA group, culture positive PJI was identified in 21 of 2,455 (0.9%) cefuroxime-administered cases and in 3 of 211 (1.4%) noncefuroxime administered cases. The most commonly isolated bacteria in both groups were coagulase negative staphylococci (CNS). There were no statistically significant differences of pathogen spectrum depending on the preoperative antibiotic regimen detected. Antibiotic resistance of isolated bacteria was significantly different in 4 of 27 (14.8%) analyzed antibiotics in THA and in 3 of 22 (13.6%) analyzed antibiotics in TKA/UKA. In all cohorts, a high occurrence of oxacillin-resistant CNS (50.0 to 100.0%) and clindamycin-resistant CNS (56.3 to 100.0%) has been observed. CONCLUSION: The use of the second-line antibiotic did not influence the pathogen spectrum or antibiotic resistance. However, an alarmingly high proportion of CNS strains was resistant to clindamycin.

Molecular mechanism of Hfq-dependent sRNA1039 and sRNA1600 regulating antibiotic resistance and virulence in Shigella sonnei.

Bacillary dysentery caused by Shigella spp. is a significant concern for human health. Small non-coding RNA (sRNA) plays a crucial role in regulating antibiotic resistance and virulence in Shigella spp. However, the specific mechanisms behind this phenomenon are still not fully understood. This study discovered two sRNAs (sRNA1039 and sRNA1600) that may be involved in bacterial resistance and virulence. By constructing deletion mutants (WT/ΔSR1039 and WT/ΔSR1600), this study found that the WT/ΔSR1039 mutants caused a two-fold increase in sensitivity to ampicillin, gentamicin and cefuroxime, and the WT/ΔSR1600 mutants caused a two-fold increase in sensitivity to cefuroxime. Furthermore, the WT/ΔSR1600 mutants caused a decrease in the adhesion and invasion of bacteria to HeLa cells (P<0.01), and changed the oxidative stress level of bacteria to reduce their survival rate (P<0.001). Subsequently, this study explored the molecular mechanisms by which sRNA1039 and sRNA1600 regulate antibiotic resistance and virulence. The deletion of sRNA1039 accelerated the degradation of target gene cfa mRNA and reduced its expression, thereby regulating the expression of pore protein gene ompD indirectly and negatively to increase bacterial sensitivity to ampicillin, gentamicin and cefuroxime. The inactivation of sRNA1600 reduced the formation of persister cells to reduce resistance to cefuroxime, and reduced the expression of type-III-secretion-system-related genes to reduce bacterial virulence by reducing the expression of target gene tomB. These results provide new insights into Hfq-sRNA-mRNA regulation of the resistance and virulence network of Shigella sonnei, which could potentially promote the development of more effective treatment strategies.

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.

The impact of antibiotic prophylaxis with intracameral cefuroxime on postoperative infectious endophthalmitis rates in a high-volume cataract surgery center.

Our purpose was to compare postoperative infectious endophthalmitis rates before and after the introduction of antibiotic prophylaxis via intracameral with cefuroxime (ATB-P IC) in a high-volume cataract surgery service. Retrospective cohort study considering patients who underwent cataract surgery at Ophthal Hospital Especializado, São Paulo, Brazil, from January/2011 to December/2019. Patients operated from 2013 to 2019 comprised the ATB-P IC group while those operated from 2011 to 2013 formed the control group without the ATB-P IC protocol. A total of 23,184 cataract surgeries were included, with 6,207 in the Control Group and 16,977 in the ATB-P Group. A significantly higher rate of endophthalmitis was observed in the control group (0.0967%) when compared to the ATB-P group (0.0177%) (p = 0.014). Surgeries performed with ATB-P showed 80% less chance of reported endophthalmitis (OR = 0.20; 95% CI 0.05-0.72; p = 0.014) than those without ATB-P. Of the six cases confirmed by culture in the control group, all tested positive for Pseudomonas aeroginosa and the only case confirmed by culture in the ATB-P group was positive for Staphylococcus epidermidis. Our findings strongly support the use of intracameral antibiotic prophylaxis with cefuroxime to reduce postoperative infectious endophthalmitis rates, and we recommend its incorporation into cataract surgery protocols.

Association between perioperative prophylaxis with cefuroxime plus metronidazole or amoxicillin/clavulanic acid and surgical site infections in paediatric uncomplicated appendectomy: a Swiss retrospective cohort study.

OBJECTIVE: We aimed to evaluate the association between post-appendectomy SSI rates and the two most commonly used regimens for perioperative antimicrobial prophylaxis in Swiss children. METHODS: We conducted a retrospective cohort study, analysing data from the Swiss national SSI surveillance database with a study period from 2014 to 2018. All hospitals undertaking paediatric appendectomies in Switzerland participate in the surveillance. We compared the cumulative incidence and odds of post-appendectomy SSI within 30 days of surgery in children ≤ 16 years of age undergoing appendectomy for uncomplicated appendicitis and receiving perioperative antimicrobial prophylaxis with cefuroxime plus metronidazole or with amoxicillin/clavulanic acid using multivariable adjusted logistic regression and propensity-score matching. RESULTS: A total of 6207 cases were recorded in the study time frame. Overall SSI cumulative incidence was 1.9% (n = 119). 4256 children (54.9% male, median (IQR) age 12 [10, 14] years) received either cefuroxime plus metronidazole (n = 2348, 53.8% male) or amoxicillin/clavulanic acid (n = 1491, 57.0% male). SSI cumulative incidence was 1.1% (25/2348) among children receiving cefuroxime plus metronidazole and 2.8% (42/1491, p < 0.001) when receiving amoxicillin/clavulanic acid. The administration of cefuroxime plus metronidazole was associated with statistically significantly lower SSI odds compared to amoxicillin/clavulanic acid (aOR 0.35, 95%CI [0.20, 0.61], p < 0.001), and this was confirmed upon propensity-score matching. CONCLUSION: We found lower odds of post-appendectomy SSI in children receiving cefuroxime plus metronidazole compared to amoxicillin/clavulanic acid. Treating amoxicillin/clavulanic acid as the baseline, only 55 children need to receive cefuroxime plus metronidazole perioperative prophylaxis to avert one SSI. Existing guidelines recommending amoxicillin/clavulanic acid may need to be revised. Trial registration ISRCTN47727811, registered retrospectively.

Association of antimicrobial perioperative prophylaxis with cefuroxime plus metronidazole or amoxicillin/clavulanic acid and surgical site infections in colorectal surgery.

OBJECTIVE: To compare intravenous (IV) amoxicillin/clavulanic acid (A/CA) to IV cefuroxime plus metronidazole (C + M) for preventing surgical site infections (SSI) in colorectal surgery. BACKGROUND: Given their spectra that include most Enterobacterales and anaerobes, C + M is commonly recommended as prophylaxis of SSI in colorectal surgery. A/CA offers good coverage of Enterobacterales and anaerobes as well, but, in contrast to C + M, it also includes Enterococcus faecalis which is also isolated from patients with SSI and could trigger anastomotic leakage. METHODS: Data from a Swiss SSI surveillance program were used to compare SSI rates after class II (clean contaminated) colorectal surgery between patients who received C + M and those who received A/CA. We employed multivariable logistic regression to adjust for potential confounders, along with propensity score matching to adjust for group imbalance. RESULTS: From 2009 to 2018, 27,922 patients from 127 hospitals were included. SSI was diagnosed in 3132 (11.2%): 278/1835 (15.1%) in those who received A/CA and 2854/26,087 (10.9%) in those who received C + M (p < 0.001). The crude OR for SSI in the A/CA group as compared to C + M was 1.45 [CI 95% 1.21-1.75]. The adjusted OR was 1.49 [1.24-1.78]. This finding persisted in a 1:1 propensity score matched cohort of 1835 patients pairs with an OR of 1.60 [1.28-2.00]. Other factors independently associated with SSI were an ASA score > 2, a longer duration of operation, and a reoperation for a non-infectious complication. Protective factors were female sex, older age, antibiotic prophylaxis received 60 to 30 min before surgery, elective operation, and endoscopic approach. CONCLUSIONS: Despite its activity against enterococci, A/CA was less effective than C + M for preventing SSI, suggesting that it should not be a first choice antibiotic prophylaxis for colorectal surgery.

Analysis of a clinical guideline for treatment and early discharge in complicated acute appendicitis. / Análisis de una guía clínica para el tratamiento y alta precoz en apendicitis aguda complicada.

OBJECTIVE: The objective of this study was to assess the results of a clinical guideline for the treatment and early discharge of patients with complicated acute appendicitis in terms of infectious complications and hospital stay. MATERIALS AND METHODS: A guideline for appendicitis treatment according to severity was created. Complicated appendicitis cases were treated with ceftriaxone-metronidazole for 48h, with discharge being approved if certain clinical and blood test criteria were met. A retrospective analytical study comparing the incidence of postoperative intra-abdominal abscess (IAA) and surgical site infection (SSI) in patients under 14 years of age to whom the new guideline was applied (Group A) vs. the historical cohort (Group B, treated with gentamicin-metronidazole for 5 days) was carried out. A prospective cohort study to assess which antibiotic therapy (amoxicillin-clavulanic acid or cefuroxime-metronidazole) proved more effective in patients meeting early discharge criteria was also conducted. RESULTS: 205 patients under 14 years of age were included in Group A, whereas 109 patients were included in Group B. IAA was present in 14.3% of patients from Group A vs. 13.8% from Group B (p= 0.83), while SSI was present in 1.9% of patients from Group A vs. 8.25% from Group B (p= 0.008). Early discharge criteria were met by 62.7% of patients from Group A. Median hospital stay decreased from 6 to 3 days. At discharge, 57% of patients received amoxicillin-clavulanic acid, whereas 43% received cefuroxime-metronidazole, with no differences being found in terms of SSI (p= 0.24) or IAA (p= 0.12). CONCLUSIONS: Early discharge reduces hospital stay without increasing the risk of postoperative infectious complications. Amoxicillin-clavulanic acid is a safe option for at-home oral antibiotic therapy.

OBJETIVO: El objetivo de este estudio es evaluar los resultados en términos de complicaciones infecciosas y estancia hospitalaria de la instauración de una guía clínica para el tratamiento y alta precoz en pacientes con apendicitis aguda complicada. MATERIAL Y METODOS: Se elaboró una guía para el tratamiento de las apendicitis en función de su grado de severidad. Las complicadas se trataron con ceftriaxona-metronidazol durante 48 h, siendo alta si cumplen ciertos criterios clínicos y analíticos. Se realizó un estudio analítico retrospectivo comparando la incidencia de abscesos intraabdominales postquirúrgicos (AIA) e infección del sitio quirúrgico (ISQ) en pacientes menores de 14 años sometidos a la nueva guía (Grupo A), respecto a una cohorte histórica (Grupo B), en la que la pauta de tratamiento era gentamicina-metronidazol 5 días. Además, se realizó un estudio de cohortes prospectivas para evaluar qué antibioterapia (amocilina-clavulánico o cefuroxima-metronidazol) es más eficaz en los pacientes que cumplen criterios de alta precoz. RESULTADOS: Se incluyeron 205 pacientes menores de 14 años en el Grupo A y 109 en el Grupo B. Presentaron AIA un 14,3% en el grupo A, frente al 13,8% en el B (p=  0,83); e ISQ un 1,9% y un 8,25% respectivamente (p=  0,008). Cumplieron criterios de alta precoz el 62,7% de los pacientes del Grupo A. La mediana de estancia disminuyó a de 6 a 3 días. Al alta, el 57% recibieron amoxicilina-clavulánico y el 43% cefuroxima-metronidazol, sin hallarse diferencias en términos de ISQ (p=  0,24) ni de AIA (p=  0,12). CONCLUSIONES: El alta precoz disminuye la estancia hospitalaria sin aumentar el riesgo de complicaciones infecciosas postquirúrgicas. La amoxicilina-clavulánico es una opción segura para la antibioterapia oral domiciliaria.

Molecular characterization of multidrug-resistant non-typeable Haemophilus influenzae with high-level resistance to cefuroxime, levofloxacin, and trimethoprim-sulfamethoxazole.

BACKGROUND: Non-typeable Haemophilus influenzae (NTHi) has become the major cause of invasive H. influenzae diseases in the post-H. influenzae type b vaccine era. The emergence of multidrug-resistant (MDR) NTHi is a growing public health problem. Herein, we investigated the molecular basis of MDR in NTHi. The isolated NTHi were subjected to antimicrobial susceptibility testing for 12 agents. Whole genome and plasmid sequencing were conducted and analyzed to identify significant genetic variations and plasmid-encoded genes conferred antibiotic resistance. RESULTS: Thirteen (50%) MDR NTHi isolates were obtained; of these, 92.3% were non-susceptible to ampicillin, 30.8% to amoxicillin-clavulanate, 61.5% to cefuroxime, 61.5% to ciprofloxacin/levofloxacin, 92.3% to trimethoprim-sulfamethoxazole, 30.8% to tetracycline, and 7.7% to azithromycin. Eight ampicillin-resistant isolates were ß-lactamase positive; of these, 6 carried blaTEM-1 and 2 carried blaROB-1, whereas 4 were ß-lactamase negative. Genetic variations in mrdA, mepA, and pbpG were correlated with amoxicillin-clavulanate non-susceptibility, whereas variations in ftsI and lpoA conferred cefuroxime resistance. Five variations in gyrA, 2 in gyrB, 3 in parC, 1 in parE, and 1 in the parC-parE intergenic region were associated with levofloxacin/ciprofloxacin non-susceptibility. Among these genes, 8 variations were linked to high-level levofloxacin resistance. Six variations in folA were associated with trimethoprim-sulfamethoxazole resistance. Plasmid-bearing tet(B) and mef(A) genes were responsible for tetracycline and azithromycin resistance in 4 and 1 MDR isolates, respectively. CONCLUSIONS: This study clarified the molecular epidemiology of MDR in NTHi. This can benefit the monitoring of drug resistance trends in NTHi and the adequate medical management of patients with NTHi infection.

IFN-γ secretion of PBMC from non-drug-allergic control persons: Considerations for the validity of a positive lymphocyte transformation test.

BACKGROUND: The lymphocyte transformation test (LTT) is used for the in vitro detection of a drug sensitization in assumed drug allergic patients. It is based on the detection of antigen (drug)-specific activation of T cells indicated by e.g. proliferation or cytokine secretion. However, occasional stimulatory effects of the drug unrelated to specific drug-allergic mechanisms can only be detected if a larger number of non-drug allergic control persons are tested with this specific drug. In this respect, the overall specificity of the LTT with ELISA read-out is summarized in several review articles, but the impact of a specific drug on the specificity has not yet been analyzed in a larger set of control persons. OBJECTIVE: Do amoxicillin, cefuroxime and clindamycin induce an interferon (IFN)-y or interleukin (IL)-5 secretion of PBMC from control persons using the LTT with ELISA read-out? METHODS: We performed LTTs with amoxicillin, cefuroxime and clindamycin and determined drug-specific IFN-γ and IL-5 secretion measured by ELISA read-out. We included PBMC from 60 non-drug allergic control persons, who were unexposed to the tested drug at the time of blood donation. RESULTS: PBMC from 12 out of 23 control persons tested with amoxicillin gave a positive stimulation index (SI > 3.0) for IFN-γ resulting in a specificity of 47.8%. The corresponding specificity was 75% for cefuroxime (5/20 if SI > 3.0) and 58.8% for clindamycin (7/17, if SI > 2.0), respectively. In a next step, we calculated the Δ IFN-γ concentration by subtracting the background IFN-γ concentration in the unstimulated sample from the stimulated sample. After stimulation with amoxicillin, a mean concentration of 21.0 pg/mL IFN-γ was secreted. The less outlier prone median concentration was 7.4 pg/mL and much higher than for cefuroxime (1.7 pg/mL) and clindamycin (1.0 pg/mL). Remarkably, IL-5 concentrations were below the detection limit (< 1 pg/mL) for all drugs in all control persons who responded to TT. CONCLUSION: Consideration of these observations may be helpful since a positive LTT result in a control patient may challenge the validity of a positive LTT result in the same experiment for a patient with assumed drug allergy.