Ceftriaxone Group Research Articles

2197. Ceftriaxone Monotherapy vs. Ceftriaxone Plus Azithromycin for the Treatment of Community-Acquired Pneumonia in Hospitalized, Non-ICU Patients

BackgroundCommunity-acquired pneumonia (CAP) is the leading infectious cause of death and severe sepsis in the United States and the fifth leading cause of death overall worldwide. Current United States guidelines for the treatment of CAP recommend empiric antibiotic therapy that covers both standard organisms as well as atypical organisms. Ceftriaxone (CTX) in combination with azithromycin (AZH) is one of the most common regimens used for the treatment of CAP; however, there are studies that show β-lactam monotherapy is as effective as a β-lactam in combination with AZH for the empiric treatment of CAP. The purpose of this study was to compare the rates of treatment failure between CTX monotherapy and CTX in combination with AZH in non-intensive care unit (ICU) inpatients.MethodsNon-ICU hospitalized patients ≥ 18 years old admitted to Saint Vincent Healthcare with a primary or secondary ICD-10 code of pneumonia from 2013 to 2018 were included. Patients were excluded if they were pregnant, admitted within 2 weeks of a previous episode of CAP, were admitted to the ICU, had cystic fibrosis, or were given antibiotics with atypical coverage (other than azithromycin) prior to admit or within 24 hours of presentation. The primary outcome was treatment failure defined as a composite of any of the following: (1) attributable mortality, (2) in vitro resistance, and (3) change of antibiotic class. Secondary outcomes included length of stay, antibiotic duration, time to oral antibiotics, and readmission within 30 days.ResultsThere were 84 and 159 patients included in the CTX and CTX+AZH groups, respectively. Baseline demographics between groups are shown in Table 1. The composite primary endpoint occurred in 22 patients (26.2%) in the CTX group and in 48 patients (30.2%) in the CTX + AZH group. After adjusting for gender, race, in hospital death, chronic obstructive pulmonary disease, length of therapy, length of stay, and systemic inflammatory response syndrome, CTX monotherapy was no less effective than CTX+AZH (aOR 0.55; 95% CI: 0.27 to 1.1; P = 0.09). The primary endpoint and secondary endpoints are shown in Tables 2 and 3, respectively.ConclusionThere was no difference between CTX monotherapy and CTX + AZH for the empiric treatment of CAP. Disclosures All authors: No reported disclosures.

460. Ceftriaxone vs. Standard of Care for Definitive Treatment of Methicillin-Susceptible Staphylococcus aureus Infections

Backgroundβ-Lactam antibiotics, specifically nafcillin, oxacillin, and cefazolin, have proven efficacy for methicillin-susceptible Staphylococcus aureus (MSSA) infections. Outpatient antimicrobial therapy (OPAT) with these agents is limited due to side effects and multiple doses required per day. Ceftriaxone, a third-generation cephalosporin, has a favorable profile for OPAT. Limited evidence supporting ceftriaxone therapy for MSSA infections prevents its widespread use.MethodsA multi-center, retrospective cohort study comparing patients who received cefazolin or nafcillin to patients who received ceftriaxone for treatment of microbiologically proven MSSA infections was conducted from February 2016 to February 2018. The primary outcome of interest was a clinical success, defined as the absence of infection-related readmission, worsening infection, or recurrent infection within 90 days. Secondary outcomes included the rate of adverse reactions, length of stay, and impact of Infectious Diseases (ID) consult.Results66 patients treated with ceftriaxone and 156 patients treated with cefazolin or nafcillin were included. Skin and soft tissue and bone and joint were the most common infections in the ceftriaxone group, whereas bacteremia was most common in the nafcillin and cefazolin group. There were significant differences in baseline age (61 years vs. 59 years; P = 0.036) and intravenous drug use (1 patient vs. 25 patients; P = 0.002) between groups. As shown in Table 1, there were significantly lower rates of clinical success with ceftriaxone compared with standard of care as a composite of all infection sites (78.8% vs. 91%; P = 0.012). No statistically significant differences were seen in safety outcomes or ID consultation. Length of stay was significantly longer in the nafcillin and cefazolin group (5.2 days vs. 12.8 days; P ≤ 0.0001).ConclusionThe results of this study indicate that patients treated with ceftriaxone for MSSA infections had significantly lower rates of clinical success compared with standard of care antibiotics. Nafcillin or cefazolin should remain as first-line agents for treatment of bone and joint infections and skin and soft-tissue infections due to MSSA. Disclosures All authors: No reported disclosures.

Effect of ceftriaxone on paired-pulse response and long-term potentiation of hippocampal dentate gyrus neurons in rats with Alzheimer-like disease

AimsGlutamatergic dysfunction is posed as a main stage in neurodegenerative disorders such as Alzheimer's disease (AD). Glutamate-mediated excitotoxicity contributes to cognitive dysfunction and cell death in AD. Ceftriaxone (CFT), a well-known upregulator of GLT-1, selectively induces the expression of glutamate transporter-1 (GLT-1) in different brain regions and therefore can be posed as a potential candidate for elimination of glutamate-induced excitotoxicity which is an early prominent event in AD brains. This study was designed to investigate the electrophysiological and behavioral effects of the β-lactam antibiotic ceftriaxone in okadaic acid (OKA)-induced model of AD. Materials and methodsMale Wistar rats divided into four control, ceftriaxone (CFT), OKA, and OKA plus ceftriaxone (OKA + CFT) groups. OKA was injected intracerebroventricularly (i.c.v., 200 ng/5 μl) into lateral ventricles and after two weeks the evoked field potential recorded from hippocampal perforant path-DG synapses in order to evaluate the effect of ceftriaxone treatment (200 mg/kg/day, i.p.) on long-term potentiation (LTP) and paired-pulse responses. Key findingsResults of this study revealed that ceftriaxone treatment significantly ameliorates the OKA-induced attenuation of field excitatory post-synaptic potential (fEPSP) slope and population spike (PS) amplitude following high-frequency stimulation and paired-pulse paradigm indicating its beneficial effects on both short-term and long-term plasticity in these neurons. Ceftriaxone also has an improving effect on OKA-induced impairment in short- and long-term memories evaluated by alternation behavior and passive avoidance tasks in rats. SignificanceTherefore, this study suggests that GLT-1 might be a promising therapeutic target for treatment of neurodegenerative disorders such as AD in the future.

Use of ceftriaxone in stroke patients, a predictor of good outcome in stroke patients: experience from a tertiary care center in North India

Post stroke pneumonia is a common cause of mortality in stroke patients and role of prophylactic antibiotics is controversial. Whether use of ceftriaxone as a prophylactic measure has any added advantage over other antibiotics is not known. A cross-sectional prospective study was conducted in the S S Lal Hospital, Institute of Medical Sciences, Banaras Hindu University, India, throughout June, 2017 to December, 2018 on the efficacy of short-term antibacterial therapy to develop post-stroke infection. We assessed the outcome of therapy by mRS at discharge which was grouped in to two categories: mRS with good outcome (0--3) and mRS with poor outcome (4--6). Similarly patients were grouped into four categories: Group 1 (no antibiotic group), Group 2 (Pipracillin plus tazobactum group), Group 3 (Ceftazidine group) and Group 4 (Ceftriaxone group). Further data was analyzed using SPSS software version 25. 366 stroke patients were analyzed for outcome with age ranging from 20 to 95 years and out of which 151 were females. Efficacy of antibiotic was analyzed between two groups: poor outcome (mRS 4--6) and good outcome (mRS 0-3) using Pearson’s Chi-square and Binary Logistic Regression. It was found that severity was significantly lower in those patients who were given ceftriaxone antibiotic with p = 0.010; odd’s ratio = 0.327; 95% CI, 1.270–8.758 respectively. Prophylactic use of ceftriaxone in stroke patients have better outcome in comparison to Pipracillin-tazobactum and Ceftrazidine.

Intravenous ceftriaxone plus clindamycin reduces breast abscess formation in severe lactational mastitis

Objective: Lactational mastitis can progress to local abscess formation if not treated promptly. The study aims to understand whether the use of intravenous cephalosporin plus clindamycin could reduce breast abscess formation when preferred as a first-line treatment instead of oral penicillin. Method: Patients who admitted to our outpatient clinic with sign and symptoms of lactational mastitis were recruited retrospectively for the study. Patients who had abscess formation on admittance were excluded. Patients were categorized into two groups according to antibiotic preference as the group I with intravenous ceftriaxone plus clindamycin and group II with oral penicillin. Groups were compared according to abscess formation in follow-up by physical examination and ultrasound. Results: A total of 64 patients with severe lactational mastitis were included. In group I (n=29), only one breast abscess with MSSA was developed. However, seven cases of breast abscess were developed in the second group (n=35). MRSA (n=4), MSSA (n=1), gram-negative bacilli (n=1) and no organism (n=1) were cultured in pus among group II. The prevalence of abscess in group I is found to be significantly lower in comparison to the control group in 12 weeks follow-up (p=0.049). Conclusions: MRSA and gr (-) bacilli are the significant agents in persistent breast abscess formation, which are resistant to oral penicillin or first/second-line cephalosporin. The ceftriaxone plus clindamycin could be used to reduce abscess formation after severe lactational mastitis, therefore, avoids unnecessary operations and hospitalization.

Comparison of Adverse Drug Reactions Between Patients Treated With Ceftaroline or Ceftriaxone: A Single-Center, Matched Cohort Study.

Little information is available on the relative tolerability of ceftaroline versus other cephalosporins in clinical practice. We sought to compare adverse drug reactions (ADRs) associated with ceftaroline with those associated with ceftriaxone in hospitalized patients. This was a retrospective, single-center matched cohort (according to age, indication, and duration) study of patients treated with ceftaroline or ceftriaxone at the VA St Louis Health Care System between 29 October 2010 and 28 March 2017, to compare rates of ADRs between the agents. Patients included received ≥2 doses of either medication to treat osteomyelitis, acute bacterial skin and skin structure infection, blood stream infection, pneumonia, infective endocarditis, septic arthritis, prosthetic joint infection, or empyema. The primary and secondary outcomes were the composite of any ADR during therapy and any ADR leading to premature discontinuation of therapy. The ADRs evaluated included rash, neutropenia, acute kidney injury, eosinophilia, thrombocytopenia, transaminitis, and hyperbilirubinemia. After matching, 50 patients per group were included and analyzed. An ADR occurred in 20% (10 of 50) of patients treated with ceftriaxone and 16% (8 of 50) of those treated with ceftaroline (P = .60). Two percent (1 of 50) of those treated with ceftriaxone and 16% (8 of 50) treated with ceftaroline had therapy discontinued owing to an ADR (P = .03). The most common ADR was eosinophilia (3 of 50) in the ceftriaxone group and rash (5 of 50) in the ceftaroline group. Ceftaroline therapy was identified as an independent risk factor for an ADR requiring premature discontinuation (odds ratio, 10.2; 95% confidence interval, 1.19-87.8; P = .03). Although there was no difference in the rates of ADRs between patients in the ceftriaxone and ceftaroline groups, significantly more ceftaroline-treated patients required premature discontinuation.

Solithromycin versus ceftriaxone plus azithromycin for the treatment of uncomplicated genital gonorrhoea (SOLITAIRE-U): a randomised phase 3 non-inferiority trial

Antibiotic-resistant gonorrhoea represents a global public health threat, and new therapies are needed. We aimed to compare the efficacy and safety of solithromycin, a fourth generation macrolide, with ceftriaxone plus azithromycin for the treatment of gonorrhoea. We did an open-label, multicentre, non-inferiority trial of patients aged 15 years or older with uncomplicated untreated genital gonorrhoea at two sites in Australia and one site in the USA. Patients were randomly assigned (1:1) to receive single dose oral solithromycin 1000 mg or intramuscular ceftriaxone 500 mg plus oral azithromycin 1000 mg. Neisseria gonorrhoeae cultures were obtained at baseline and test of cure (day 7 ± 2). The primary outcome was the proportion of patients with eradication of genital N gonorrhoeae based on culture at test of cure, assessed in the microbiological intention-to-treat (mITT) population, which included all randomly assigned patients who received any dose of study drug and had a positive genital culture for N gonorrhoeae at baseline. Non-inferiority of solithromycin was to be concluded if the lower limit of the 95% CI for the between-group differences was greater than -10%. Safety was analysed in all patients who received any dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT02210325. Between Sept 3, 2014, and Aug 27, 2015, 262 patients were randomly assigned and 261 received treatment (130 in the solithromycin group and 131 in the ceftriaxone plus azithromycin group). In the mITT population, 99 (80%) of 123 patients in the solithromycin group and 109 (84%) of 129 patients in the ceftriaxone plus azithromycin group had N gonorrhoeae eradication at test of cure (difference -4·0%, 95% CI -13·6 to 5·5), thus solithromycin did not meet the criterion for non-inferiority at the prespecified -10% margin. The frequency of adverse events was higher in the solithromycin group than the ceftriaxone plus azithromycin group (69 [53%] of 130 patients vs 45 [34%] of 131 patients), the most common of which were diarrhoea (31 [24%] of 130 patients vs 20 [15%] of 131 patients), and nausea (27 [21%] of 130 patients vs 15 [11%] of 131 patients). Solithromycin as a single 1000 mg dose is not a suitable alternative to ceftriaxone plus azithromycin as first-line treatment for gonorrhoea. If insufficient duration of solithromycin exposure at the infection site in a subset of individuals was the reason for treatment failures, this might be adequately addressed with dose adjustment. However, any further trials with longer dosing need to consider the potential risk of gastrointestinal effects and liver enzyme elevations. Cempra Pharmaceuticals.

Clinical impact of routine somatostatin analogues administration after pancreatoduodenectomy: a case-matched comparison according to fistula risk score, ASA and surgical technique

The aim of the present study was to investigate whether the incidence of surgical site infection after pancreatoduodenectomy decreased after changing the prophylactic antibiotic to a third-generation cephalosporin in patients with unknown preoperative bile culture results after biliary drainage.In a retrospective study of 138 pancreatoduodenectomy patients who underwent endoscopic biliary stenting and for whom recent preoperative bile culture results were unavailable, cefazolin sodium hydrate was administered as perioperative prophylactic antibiotic therapy from 2010 to 2014 (n = 69); whereas ceftriaxone was administered from 2014 to 2017 (n = 69) based on the results of institutional culture surveillance. The incidence of surgical site infection was compared between the two groups and the risk factor of surgical site infection was also evaluated.The incidence of overall surgical site infection in the ceftriaxone group was significantly lower than that in the cefazolin sodium hydrate group for both Clavien-Dindo grade ≥II (28% versus 52%, P = .005) and Clavien-Dindo grade ≥IIIa (20% vs 41%, P = .016). A multivariate analysis revealed that the prophylactic administration of cefazolin sodium hydrate was associated with a higher incidence of overall surgical site infection in both Clavien-Dindo grade ≥II and Clavien-Dindo grade ≥IIIa (odds ratio 2.56, P = .019; odds ratio 3.03, P = .020, respectively). In the cefazolin sodium hydrate group, most of the patients with positive perioperative cultures had Enterobacteriaceae, which were intrinsically resistant to cefazolin sodium hydrate, and most were susceptible to ceftriaxone.The prophylactic administration of third-generation cephalosporin reduced the incidence of surgical site infection after pancreatoduodenectomy in patients who underwent preoperative endoscopic biliary stenting.

Gentamicin compared with ceftriaxone for the treatment of gonorrhoea (G-ToG): a randomised non-inferiority trial

SummaryBackgroundGonorrhoea is a common sexually transmitted infection for which ceftriaxone is the current first-line treatment, but antimicrobial resistance is emerging. The objective of this study was to assess the effectiveness of gentamicin as an alternative to ceftriaxone (both combined with azithromycin) for treatment of gonorrhoea.MethodsG-ToG was a multicentre, parallel-group, pragmatic, randomised, non-inferiority trial comparing treatment with gentamicin to treatment with ceftriaxone for patients with gonorrhoea. The patients, treating physician, and assessing physician were masked to treatment but the treating nurse was not. The trial took place at 14 sexual health clinics in England. Adults aged 16–70 years were eligible for participation if they had a diagnosis of uncomplicated genital, pharyngeal, or rectal gonorrhoea. Participants were randomly assigned to receive a single intramuscular dose of either gentamicin 240 mg (gentamicin group) or ceftriaxone 500 mg (ceftriaxone group). All participants also received a single 1 g dose of oral azithromycin. Randomisation (1:1) was stratified by clinic and performed using a secure web-based system. The primary outcome was clearance of Neisseria gonorrhoeae at all initially infected sites, defined as a negative nucleic acid amplification test 2 weeks post treatment. Primary outcome analyses included only participants who had follow-up data, irrespective of the baseline visit N gonorrhoeae test result. The margin used to establish non-inferiority was a lower confidence limit of 5% for the risk difference. This trial is registered with ISRCTN, number ISRCTN51783227.FindingsOf 1762 patients assessed, we enrolled 720 participants between Oct 7, 2014, and Nov 14, 2016, and randomly assigned 358 to gentamicin and 362 to ceftriaxone. Primary outcome data were available for 306 (85%) of 362 participants allocated to ceftriaxone and 292 (82%) of 358 participants allocated to gentamicin. At 2 weeks after treatment, infection had cleared for 299 (98%) of 306 participants in the ceftriaxone group compared with 267 (91%) of 292 participants in the gentamicin group (adjusted risk difference −6·4%, 95% CI −10·4% to −2·4%). Of the 328 participants who had a genital infection, 151 (98%) of 154 in the ceftriaxone group and 163 (94%) of 174 in the gentamicin group had clearance at follow-up (adjusted risk difference −4·4%, −8·7 to 0). For participants with a pharyngeal infection, a greater proportion receiving ceftriaxone had clearance at follow-up (108 [96%] in the ceftriaxone group compared with 82 [80%] in the gentamicin group; adjusted risk difference −15·3%, −24·0 to −6·5). Similarly, a greater proportion of participants with rectal infection in the ceftriaxone group had clearance (134 [98%] in the ceftriaxone group compared with 107 [90%] in the gentamicin group; adjusted risk difference −7·8%, −13·6 to −2·0). Thus, we did not find that a single dose of gentamicin 240 mg was non-inferior to a single dose of ceftriaxone 500 mg for the treatment of gonorrhoea, when both drugs were combined with a 1 g dose of oral azithromycin. The side-effect profiles were similar between groups, although severity of pain at the injection site was higher for gentamicin (mean visual analogue pain score 36 of 100 in the gentamicin group vs 21 of 100 in the ceftriaxone group).InterpretationGentamicin is not appropriate as first-line treatment for gonorrhoea but remains potentially useful for patients with isolated genital infection, or for patients who are allergic or intolerant to ceftriaxone, or harbour a ceftriaxone-resistant isolate. Further research is required to identify and test new alternatives to ceftriaxone for the treatment of gonorrhoea.FundingUK National Institute for Health Research.

Effect of Dahuang Danpi Decoction on Lactobacillus bulgaricus growth and metabolism: In vitro study.

Gut flora plays an essential role in disease and health. A traditional Chinese herb formula, Dahuang Danpi Decoction (DDD) can alleviate several gastrointestinal diseases.In the present study, we assessed the effect of DDD on the growth and metabolism of Lactobacillus bulgaricus. L bulgaricus was cultured in MRS with 40 mg/ml (high), 10 mg/ml (medium), and 2.5 mg/ml (low) of DDD, Ceftriaxone and blank (control). The growth of L bulgaricus was measured by optical density. The levels of L-lactic acid and D-lactic acid were also measured.Compared to the control group, the concentrations of L bulgaricus in the medium and the high concentrations DDD groups were significantly higher (P < .001 for all), while the concentrations of L bulgaricus in the ceftriaxone groups were significantly lower. In the 3 DDD groups, the L- lactic acid levels were significantly higher than those in the control group and the ceftriaxone groups (P < .001 for all), and the L-lactic acid level was the highest in the high DDD group. Similarly, the D-lactic acid level in the high concentration DDD group was significantly higher than those in the medium and low concentration DDD groups, the control group and the ceftriaxone groups. Both the L-lactic acid and D-lactic acid levels were lower than those in the control group and the DDD groups.DDD could dose-dependently promote the growth of L bulgaricus and enhance the secretion of L-lactic acid and D-lactic acid, which suggests DDD may be able to interact with the probiotics, improve the gut microbiota, and serve in the prevention and treatment of dysbiosis.

Evaluation of the Effect of Ceftriaxone on Lipid Peroxidation and Antioxidant Levels in Mice

Lipid peroxidation generates free radicals. These free radicals are scavenged by antioxidant defense mechanisms. An imbalance between the free radicals generation and antioxidant mechanisms can result in tissue damage. Several drugs are known to induce lipid peroxidation which can be responsible for their toxic potential. Hence the current study was planned to assess the effect of ceftriaxone, a third generation cephalosporin, on lipid peroxidation and levels of antioxidants in albino mice. Ceftriaxone was injected intraperitoneally at two doses - 100 mg/kg body weight; 200 mg/kg body weight – to albino mice. TBARS (Thiobarbituric acid reactive substance) levels in plasma, erythrocytes as well as tissue and the antioxidant enzymes activities were estimated. The data from ceftriaxone groups was analyzed with control group using ANOVA and Dunnett’s test as post hoc. Ceftriaxone (100 mg/kg body weight) did not alter TBARS levels compared to control. Ceftriaxone - 200 mg/kg body weight, has significantly increased TBARS levels. The activities of antioxidant enzymes were significantly decreased by ceftriaxone at these doses. The present study demonstrates that ceftriaxone has the potential for lipid peroxidation induction and reduction in the antioxidant enzymes acitivities in albino mice.

COST-EFFECTIVENESS ANALYSIS OF CEFTRIAXONE AND NON-CEFTRIAXONE ON TYPHOID FEVER PATIENTS

Objective: This study aimed to evaluate the cost-effectiveness of ceftriaxone and non-ceftriaxone therapies in patients with typhoid fever.Methods: The applied method was a cost-effectiveness analysis. Data were retrospectively collected, and sampling was performed using totalsampling based on medical records and hospital information systems. Subjects were limited to patients diagnosed with typhoid fever and usingceftriaxone or non-ceftriaxone antibiotics. A total of 15 patients were investigated, comprising 10 patients on ceftriaxone and five patients using nonceftriaxoneantibiotics. Effectiveness was evaluated by the length of hospitalization. The cost was a median of total costs, consisting of the cost of thedrug, concomitant drugs, medical equipment, laboratory tests, doctor, health-care services, and hospitalization.Results: The results showed the effectiveness of ceftriaxone (3.80±0.789 days) did not differ with the non-ceftriaxone drugs (3.40±1.635 days).However, the total cost of ceftriaxone (Rp 1,929,355) was less than that of non-ceftriaxone antibiotics (Rp 2,787,003). The average cost-effectivenessratio of ceftriaxone group (Rp 507,725/effectiveness) was lower compared to the non-ceftriaxone (Rp 819,707/effectiveness).Conclusions: This study results showed that ceftriaxone was more cost-effective than non-ceftriaxone antibiotics.

1969. Comparison of Adverse Event Rates Between Patients Treated With Ceftaroline or Ceftriaxone

BackgroundAt the VA St. Louis Health Care System 17.3% of patients treated with ceftaroline developed an adverse drug reaction (ADR). This evaluation compares ADR rates between patients treated with ceftaroline and those treated with ceftriaxone.MethodsThis was a retrospective, single-center cohort study of patients treated with ceftaroline or ceftriaxone at the VA St. Louis Health Care System between October 29, 2010 and March 28, 2017. Patients included received at least two doses of either medication and were treated for osteomyelitis, acute bacterial skin and skin structure infections, blood stream infections, pneumonia, infective endocarditis, septic arthritis, prosthetic joint infections, or an empyema. Once identified, patients were matched 1:1 utilizing the nearest neighbor method accounting for age, indication, and duration of therapy. The primary and secondary outcomes were the composite of any ADR while on therapy and any ADR leading to therapy discontinuation, respectively. Adverse reactions evaluated were rash, neutropenia, acute kidney injury, eosinophilia, thrombocytopenia, transaminitis, and hyperbilirubinemia.ResultsThere were 75 unique ceftaroline-treated and 312 ceftriaxone-treated patients identified. After propensity score matching, 50 patients per group were included and analyzed. The mean age of patients was 65.4 and 63.4 years (P = 0.47), and the mean duration of therapy was 14.5 and 17 days (P = 0.90), ceftriaxone compared with ceftaroline respectively. Any ADR occurred in 20% (10/50) of patients treated with ceftriaxone and 16% (8/50) of patients treated with ceftaroline (P = 0.60). One patient (2%) treated with ceftriaxone and 16% (8/50) treated with ceftaroline had therapy discontinued for an ADR (P = 0.03). The most common ADR was eosinophilia (3/50) in the ceftriaxone group and rash (5/50) in the ceftaroline group. In multivariate regression, ceftaroline therapy was identified as an independent risk factor for development of an ADR requiring discontinuation (OR 10.2; 95% CI 1.19–87.8), P = 0.03).ConclusionThere was no difference in the development of any ADR between patients treated with ceftriaxone or ceftaroline, but patients treated with ceftaroline had more ADRs leading to therapy discontinuation.Disclosures All authors: No reported disclosures.

Third-generation cephalosporin for antimicrobial prophylaxis in pancreatoduodenectomy in patients with internal preoperative biliary drainage

The aim of the present study was to investigate whether the incidence of surgical site infection after pancreatoduodenectomy decreased after changing the prophylactic antibiotic to a third-generation cephalosporin in patients with unknown preoperative bile culture results after biliary drainage. In a retrospective study of 138 pancreatoduodenectomy patients who underwent endoscopic biliary stenting and for whom recent preoperative bile culture results were unavailable, cefazolin sodium hydrate was administered as perioperative prophylactic antibiotic therapy from 2010 to 2014 (n = 69); whereas ceftriaxone was administered from 2014 to 2017 (n = 69) based on the results of institutional culture surveillance. The incidence of surgical site infection was compared between the two groups and the risk factor of surgical site infection was also evaluated. The incidence of overall surgical site infection in the ceftriaxone group was significantly lower than that in the cefazolin sodium hydrate group for both Clavien-Dindo grade ≥II (28% versus 52%, P = .005) and Clavien-Dindo grade ≥IIIa (20% vs 41%, P = .016). A multivariate analysis revealed that the prophylactic administration of cefazolin sodium hydrate was associated with a higher incidence of overall surgical site infection in both Clavien-Dindo grade ≥II and Clavien-Dindo grade ≥IIIa (odds ratio 2.56, P = .019; odds ratio 3.03, P = .020, respectively). In the cefazolin sodium hydrate group, most of the patients with positive perioperative cultures had Enterobacteriaceae, which were intrinsically resistant to cefazolin sodium hydrate, and most were susceptible to ceftriaxone. The prophylactic administration of third-generation cephalosporin reduced the incidence of surgical site infection after pancreatoduodenectomy in patients who underwent preoperative endoscopic biliary stenting.

Activity of fixed direct electrical current in experimental Staphylococcus aureus foreign-body osteomyelitis

Fixed DC was compared to ceftriaxone, ceftriaxone with 200 μA fixed DC, or no treatment in a rat model of methicillin-susceptible Staphylococcus aureus foreign-body osteomyelitis. After 3 weeks, fewer bacteria were present in bones of the ceftriaxone group (5.71 log10cfu/g [P = 0.0004]) and the ceftriaxone/DC group (3.53 log10cfu/g [P = 0.0002]) than untreated controls (6.70 log10cfu/g). Fewer bacteria were present in the ceftriaxone/DC group than in the ceftriaxone-alone and DC-alone groups (P = 0.0012 and 0.0008, respectively). There were also fewer bacteria on the implanted wires in the groups treated with ceftriaxone (5.47 log10cfu/cm2) or ceftriaxone/DC (2.82 log10cfu/cm2) than in the untreated controls (6.44 log10cfu/cm2 [P = 0.0003 and 0.0002, respectively]). There were fewer bacteria in the ceftriaxone/DC rats than in the ceftriaxone-alone– and fixed DC-alone–treated rats (P = 0.0017 and 0.0016, respectively). Fixed DC with an antibiotic may be useful for treating foreign-body infections caused by S. aureus.

Clinical Efficacy Of Ceftriaxone Versus Ciprofloxacin In Paediatric Enteric Fever

Objective: Determination of the clinical effectiveness of ciprofloxacin versus ceftriaxone in children with enteric fever on the basis of defervescence within 72 hours of commencement of treatment. Duration and Place of Study: This randomized controlled trial was carried out from 15th May to 15th November 2017 in pediatrics units of Benazir Bhutto Shaheed Teaching Hospital Abbottabad and Jinnah International Hospital Abbottabad. Methodology: 90 children with uncomplicated enteric fever were admitted and divided randomly into two groups, Group A was administered I/V Ceftriaxone 75mg/kg OD and Group B was given I/V Ciprofloxacin 10mg/kg BD for seven days. Response to drug was taken as defervescence within 72 hours while continued fever after 72 hours was taken as no response. The data was analyzed by using SPSS Version 21.00. Results: In our research study 53(58.9%) children were male and 37(41.1%) patients were female. The mean age was 8.43±3.17 years encompassing 4 to 14 years, mean weight of the patients in kg was 29.54±10.8 kg. Efficacy of ceftriaxone group was 93.3% while in ciprofloxacin group 62.2% patients became afebrile in 72 hours. The proportion of achieving defervescence within 72 hours was higher with ceftriaxone than with ciprofloxacin Conclusion: Ceftriaxone is more efficacious in terms of achieving defervescence than ciprofloxacin in children having enteric fever.

Can the Ceftriaxone Breakpoints Be Increased Without Compromising Patient Outcomes?

BackgroundIn 2010, the Clinical Laboratory and Standards Institute recommended a 3-fold lowering of ceftriaxone breakpoints to 1 mcg/mL for Enterobacteriaceae. Supportive clinical data at the time were from fewer than 50 patients. We compared the clinical outcomes of adults with Enterobacteriaceae bloodstream infections treated with ceftriaxone compared with matched patients (with exact matching on ceftriaxone minimum inhibitory concentrations [MICs]) treated with extended-spectrum agents to determine if ceftriaxone breakpoints could be increased without negatively impacting patient outcomes.MethodsA retrospective cohort study was conducted at 3 large academic medical centers and included patients with Enterobacteriaceae bacteremia with ceftriaxone MICs of 2 mcg/mL treated with ceftriaxone or extended-spectrum β-lactams (ie, cefepime, piperacillin/tazobactam, meropenem, or imipenem/cilastatin) between 2008 and 2014; 1:2 nearest neighbor propensity score matching was performed to estimate the odds of recurrent bacteremia and mortality within 30 days.ResultsPropensity score matching yielded 108 patients in the ceftriaxone group and 216 patients in the extended-spectrum β-lactam group, with both groups well-balanced on demographics, preexisting medical conditions, severity of illness, source of bacteremia, and source control interventions. No difference in recurrent bacteremia (odds ratio [OR], 1.16; 95% confidence interval [CI], 0.49–2.73) or mortality (OR, 1.27; 95% CI, 0.56–2.91) between the treatment groups was observed for patients with isolates with ceftriaxone MICs of 2 mcg/mL. Only 6 isolates (1.6%) with ceftriaxone MICs of 2 mcg/mL were extended-spectrum β-lactamase (ESBL)–producing.ConclusionsOur findings suggest that patient outcomes are similar when receiving ceftriaxone vs extended-spectrum agents for the treatment of Enterobacteriaceae bloodstream infections with ceftriaxone MICs of 2 mcg/mL. This warrants consideration of adjusting the ceftriaxone susceptibility breakpoint from 1 to 2 mcg/mL, as a relatively small increase in the antibiotic breakpoint could have the potential to limit the use of large numbers of extended-spectrum antibiotic agents.

Preventive Antibiotics in Stroke Study (PASS): A cost-effectiveness study.

To evaluate the cost-effectiveness of preventive ceftriaxone vs standard stroke unit care without preventive antimicrobial therapy in acute stroke patients. In this multicenter, randomized, open-label trial with masked endpoint assessment, 2,550 patients with acute stroke were included between 2010 and 2014. Economic evaluation was performed from a societal perspective with a time horizon of 3 months. Volumes and costs of direct, indirect, medical, and nonmedical care were assessed. Primary outcome was cost per unit of the modified Rankin Scale (mRS) and per quality-adjusted life year (QALY) for cost-effectiveness and cost-utility analysis. Incremental cost-effectiveness analyses were performed. A total of 2,538 patients were available for the intention-to-treat analysis. For the cost-effectiveness analysis, 2,538 patients were available for in-hospital resource use and 1,453 for other resource use. Use of institutional care resources, out-of-pocket expenses, and productivity losses was comparable between treatment groups. The mean score on mRS was 2.38 (95% confidence interval [CI] 2.31-2.44) vs 2.44 (95% CI 2.37-2.51) in the ceftriaxone vs control group, the decrease by 0.06 (95% CI -0.04 to 0.16) in favor of ceftriaxone treatment being nonsignificant. However, the number of QALYs was 0.163 (95% CI 0.159-0.166) vs 0.155 (95% CI 0.152-0.158) in the ceftriaxone vs control group, with the difference of 0.008 (95% CI 0.003-0.012) in favor of ceftriaxone (p = 0.006) at 3 months. The probability of ceftriaxone being cost-effective ranged between 0.67 and 0.89. Probability of 0.75 was attained at a willing-to-pay level of €2,290 per unit decrease in the mRS score and of €12,200 per QALY. Preventive ceftriaxone has a probability of 0.7 of being less costly than standard treatment per unit decrease in mRS and per QALY gained.

The efficacy of ampicillin compared with ceftriaxone on preventing cesarean surgical site infections: an observational prospective cohort study

BackgroundCesarean surgical site infections (SSIs) can be prevented by proper preoperative antibiotic prophylaxis. Differences in antibiotic selection in clinical practice exist according to obstetricians’ preferences despite clear guidelines on preoperative antibiotic prophylaxis. This study aimed to compare the efficacy of ampicillin and ceftriaxone in preventing cesarean SSIs.MethodsThe observational prospective cohort study was conducted at a tertiary hospital in Thailand from 1 January 2007 to 31 December 2012. Propensity scores for ceftriaxone prophylaxis were calculated from potential influencing confounders. The cesarean SSI rates of the ceftriaxone group vs. those of the ampicillin prophylactic group were estimated by multilevel mixed-effects Poisson regression nested by propensity score.ResultsData of 4149 cesarean patients were collected. Among these, 911 patients received ceftriaxone whereas 3238 patients received ampicillin as preoperative antibiotic prophylaxis. The incidence of incisional SSIs was (0.1% vs. 1.2%; p = 0.001) and organ space SSIs was (1.2% vs. 2.9%; p = 0.003) in the ceftriaxone group compared with the ampicillin group. After adjusting for confounders, the rate ratios of incisional and organ/space SSIs in the ceftriaxone compared with the ampicillin group did not differ (RR, 0.23; 95% CI 0.03–1.78), and (RR, 1.62; 95% CI 0.83–3.18), respectively.ConclusionThese data indicate no difference exists between ampicillin and ceftriaxone to prevent SSIs after cesarean section. Ampicillin may be used as antibiotic prophylaxis in cesarean section.

Ceftriaxone promotes the emergence of AmpC-overproducing Enterobacteriaceae in gut microbiota from hospitalized patients.

Epidemiological data suggest that ceftriaxone may promote the emergence of commensal AmpC-overproducing Enterobacteriaceae because of a high biliary excretion. We tested this hypothesis in hospitalized patients either treated by ceftriaxone alone or receiving no antibiotics. Hospitalized patients with no previous antibiotics or hospitalization in the last 3months, treated only with ceftriaxone, were prospectively included. For each ceftriaxone-treated patient, a control patient receiving no antibiotics was included. Clinical data and stools were collected at T0 (before antibiotics) and T1 (at the end of ceftriaxone treatment or at discharge) and T2 (3-6months after T1) for the ceftriaxone-treated patients and at T0 and T1 for control patients. Third-generation cephalosporin-resistant Enterobacteriaceae were detected, identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF), and characterized genetically. Clonal relatedness was evaluated by random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR). Fifteen ceftriaxone and 22 control patients were included. Patients' characteristics did not differ. At T0, 2/15 ceftriaxone-treated versus 1/22 control patients carried third-generation cephalosporin-resistant Enterobacteriaceae (p = 0.6). At T1, 4/15 (27%) ceftriaxone-treated patients carried AmpC producers versus 0/22 control patients (p = 0.02). Additionally, two and three subjects carried extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae in the ceftriaxone and control groups, respectively (p = 1). At T2, three ceftriaxone-treated patients still carried AmpC-producing Enterobacteriaceae with the same RAPD profile as at T1. In hospitalized subjects with no other selective pressure, treatment by ceftriaxone alone promotes the gut colonization by AmpC-overproducing Enterobacteriaceae in over a quarter of patients, with a persistent carriage after the end of antibiotic exposure. The ecological impact of ceftriaxone should not be underestimated.