Synergistic bactericidal activity of a novel dual ß-lactam combination against methicillin-resistant Staphylococcus aureus.

OBJECTIVES: MRSA is a major cause of hospital-acquired and community-acquired infections. Treatment options for MRSA are limited because of the rapid development of ß-lactam resistance. Combining antibiotics offers an affordable, time-saving, viable and efficient approach for developing novel antimicrobial therapies. Both amoxicillin and cefdinir are oral ß-lactams with indications for a wide range of bacterial infections and mild side effects. This study aimed to investigate the in vitro and in vivo efficacy of combining these two ß-lactams against MRSA strains. METHODS: Fourteen representative prevalent MRSA strains with diverse sequence types (STs) were tested with a combination of amoxicillin and cefdinir, using chequerboard and time-kill assays. The Galleria mellonella larvae infection model was used to evaluate the in vivo efficacy of this dual combination against the community-acquired MRSA (CA-MRSA) strain USA300 and the hospital-acquired MRSA (HA-MRSA) strain COL. RESULTS: The chequerboard assay revealed a synergistic activity of the dual amoxicillin/cefdinir combination against all tested MRSA strains, with fractional inhibitory concentration index (FICI) values below 0.5 and at least a 4-fold reduction in the MICs of both antibiotics. Time-kill assays demonstrated synergistic bactericidal activity of this dual combination against the MRSA strain USA300 and strain COL. Moreover, in vivo studies showed that the administration of amoxicillin/cefdinir combination to G. mellonella larvae infected with MRSA strains significantly improved the survival rate up to 82%, which was comparable to the efficacy of vancomycin. CONCLUSIONS: In vitro and in vivo studies indicate that the dual combination of amoxicillin/cefdinir demonstrates a synergistic bactericidal efficacy against MRSA strains of various STs. Further research is needed to explore its potential as a treatment option for MRSA infections.

Renin-angiotensin inhibitors reduce thrombotic complications in Essential Thrombocythemia and Polycythemia Vera patients with arterial hypertension.

Essential Thrombocythemia (ET) and Polycythemia Vera (PV) are chronic myeloproliferative neoplasms (MPNs) characterized by thrombotic and hemorrhagic complications, leading to a high risk of disability and mortality. Although arterial hypertension was found to be the most significant modifiable cardiovascular (CV) risk factor in the general population, little is known about its role in MPNs as well as a possible role of renin-angiotensin system inhibitors (RASi) in comparison with other anti-hypertensive treatments. We investigated a large cohort of 404 MPN adult patients, 133 diagnosed with PV and 271 with ET. Over half of the patients (53.7%) reported hypertension at MPN diagnosis. The 15-year cumulative incidence of thrombotic-adverse events (TAEs) was significantly higher in patients with hypertension (66.8 ± 10.3% vs 38.5 ± 8.4%; HR = 1.83; 95%CI 1.08-3.1). Multivariate analysis showed that PV diagnosis and hypertension were independently associated with a higher risk of developing TAEs (HR = 3.5; 95%CI 1.928-6.451, p < 0.001 and HR = 1.8; 95%CI 0.983-3.550, p = 0.05, respectively). In multivariate analysis, the diagnosis of PV confirmed a significant predictive role in developing TAEs (HR = 4.4; 95%CI 1.92-10.09, p < 0.01), also considering only MPN patients with hypertension. In addition, we found that the use of RASi showed a protective effect from TAEs both in the whole cohort of MPN with hypertension (HR = 0.46; 95%CI 0.21-0.98, p = 0.04) and in the subgroup of thrombotic high-risk score patients (HR = 0.49; 95%CI 0.24-1.01, p = 0.04). In particular, patients with ET and a high risk of thrombosis seem to benefit most from RASi treatment (HR = 0.27; 95%CI 0.07-1.01, p = 0.03). Hypertension in MPN patients represents a significant risk factor for TAEs and should be adequately treated.

The L-shaped correlation between systolic blood pressure and short-term and long-term mortality in patients with cerebral hemorrhage.

BACKGROUND: A large amount of evidence has shown the necessity of lowering blood pressure (BP) in patients with acute cerebral hemorrhage, but whether reducing BP contributes to lower short-term and long-term mortality in these patients remains uncertain. AIMS: We aimed to explore the association between BP, including systolic and diastolic BP, during intensive care unit (ICU) admission and 1-month and 1-year mortality after discharge of patients with cerebral hemorrhage. METHODS: A total of 1085 patients with cerebral hemorrhage were obtained from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Maximum and minimum values of systolic and diastolic BP in these patients during their ICU stay were recorded, and endpoint events were defined as the 1-month mortality and 1-year mortality after the first admission. Multivariable adjusted models were performed for the association of BP with the endpoint events. RESULTS: We observed that patients with hypertension were likely to be older, Asian or Black and had worse health insurance and higher systolic BP than those without hypertension. The logistic regression analysis showed inverse relationships between systolic BP-min (odds ratio (OR) = 0.986, 95% CI 0.983-0.989, P < 0.001) and diastolic BP-min (OR = 0.975, 95% CI 0.968-0.981, P < 0.001) and risks of 1-month, as well as 1-year mortality when controlling for confounders including age, sex, race, insurance, heart failure, myocardial infarct, malignancy, cerebral infarction, diabetes and chronic kidney disease. Furthermore, smooth curve analysis suggested an approximate L-shaped association of systolic BP with the risk of 1-month mortality and 1-year mortality. Reducing systolic BP in the range of 100-150 mmHg has a lower death risk in these patients with cerebral hemorrhage. CONCLUSION: We observed an L-shaped association between systolic BP levels and the risks of 1-month and 1-year mortality in patients with cerebral hemorrhage, which supported that lowering BP when treating an acute hypertensive response could reduce short-term and long-term mortality.

Elevated SIRT2 of serum exosomes is positively correlated with diagnosis of acute ischemic stroke patients.

BACKGROUND: Silent Information Regulator 2 (SIRT2) protein inhibition has been shown to play a neuroprotective role in acute ischemic stroke (AIS) in mice. However, its role in AIS patients has not been fully understood. In this study, we aimed to analyze SIRT2 protein expression in serum exosomes of AIS and non-AIS patients, and evaluate its potential role in diagnosis and prognosis of AIS. METHODS: Serum exosomes from 75 non-AIS subjects and 75 AIS patients were isolated. The SIRT2 protein levels in exosomes were analyzed using enzyme linked immunosorbent assay (ELISA). The National Institutes of Health Stroke Scale (NIHSS) was used to evaluate the severity of the disease. The modified Rankin Scale (mRS) was employed to assess the functional outcomes of the patients at 3-months following stroke onset. RESULTS: The SIRT2 protein concentration of serum exosomes were higher in AIS patients than non-AIS patients (p < 0.001). Furthermore, the receiver operative characteristic curve (ROC) demonstrated that higher serum exosome SIRT2 could differentiate AIS patients from non-AIS patients with a sensitivity of 81.3% and a specificity of 75.3%. The area under the curve was 0.838 (95% CI: 0.775, 0.902). Additionally, higher SIRT2 concentration of serum exosomes were associated with NIHSS ≥ 4 (p < 0.001) and mRS ≥ 3 (p = 0.025) in AIS patients. The ROC analysis showed SIRT2 could discriminate stroke with NIHSS ≥ 4 from mild stroke (NIHSS < 4) with a sensitivity of 75.0% and a specificity of 69.6%. The area under the curve was 0.771 (95% CI: 0.661,0.881). Similarly, the test showed SIRT2 could differentiate between AIS patients with mRS ≥ 3 from those with mRS < 3 with a sensitivity of 78.3% and a specificity of 51.9%. The area under the curve was 0.663 (95% CI: 0.531,0.796). The logistic regression analysis revealed that SIRT2 concentration in serum exosomes can independently predict the diagnosis of AIS (odd ratio = 1.394, 95%CI 1.231-1.577, p < 0.001) and higher NIHSS scores (≥ 4) (odd ratio = 1.258, 95%CI 1.084-1.460, p = 0.002). However, it could not independently predict the prognosis of AIS (odd ratio = 1.065, 95%CI 0.983-1.154, p = 0.125). CONCLUSION: The elevation of SIRT2 in serum exosomes may be a valuable biomarker of AIS, which may be a potential diagnostic tool to facilitate decision making for AIS patients.

Utilization of nonguideline concordant antibiotic treatment following acute otitis media in children in the United States.

PURPOSE: Acute otitis media (AOM) is a common indication for antibiotics in children. We sought to characterize the frequency of nonguideline concordant antibiotic therapy for AOM in the United States, by agent and duration. METHODS: Using national administrative claims data (2016-2019), we identified children aged 6 months to 17 years with an oral antibiotic dispensed within 3 days of a new diagnosis of suppurative AOM. Use of nonguideline concordant agents and durations, defined based on national treatment guidelines, were summarized by age, race, rurality, region, and insurance type. Subsequent oral antibiotic dispensing within the year after AOM diagnosis was also evaluated. We created sunburst diagrams to visualize longitudinal patterns of within-person antibiotic utilization for AOM, by agent and duration. RESULTS: We identified 789 424 eligible commercially-insured and 502 239 medicaid-insured children. Among commercially insured children, 35% received nonguideline concordant agents for AOM, including cefdinir (16%), amoxicillin-clavulanate (12%), and azithromycin (7%). Fewer children age <2 years received a nonguideline concordant initial agent (27%) compared to age ≥6 years (41%). More children age <2 years received three or more antibiotics over the following year (34% vs. 3% for children age ≥6 years). The most common treatment duration was 10 days for all ages; treatment duration for the initial antibiotic was nonguideline concordant for 95% and 89% of children age 2-5 years and ≥6 years, respectively. Patterns were similar for medicaid-insured children. CONCLUSIONS: Nonguideline concordant antibiotic use is common when treating AOM in children, including use of broad-spectrum agents and longer-than-recommended antibiotic durations.

Emergent "Bloody Diarrhea" Associated with the Use of Oral Cefdinir in Young Children: A Brief Report and Review of Literature.

BACKGROUND: Cefdinir is an extended-spectrum, third-generation, oral cephalosporin widely used in pediatric population to treat common bacterial infections, including otitis media and streptococcal pharyngitis. It is considered a safe and well-tolerated alternative to penicillin and macrolides. CASE REPORT: This report describes a case series of 3 infants presenting to the emergency department for evaluation of "bloody diarrhea." The parents noticed red stools when their children were started on oral cefdinir when they were previously receiving iron-containing preparations. Reddish-colored heme-negative stools observed in all cases were due to the interaction of the drug with supplemental iron or iron-containing formula feeds. This adverse effect was reversible on discontinuation of cefdinir. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Red stools due to cefdinir is an underreported benign adverse drug reaction with fewer than 10 cases described in the literature. Thorough history taking with an appropriate focus on diet and drug history are essential to avoid parental anxiety, unnecessary patient workup, and economic burden to the caregivers in these cases. Awareness of this unusual adverse effect among emergency physicians could prevent further inconvenience for already overburdened health systems.

Novel Thiazolylketenyl Quinazolinones as Potential Anti-MRSA Agents and Allosteric Modulator for PBP2a.

Bacterial infections caused by methicillin-resistant Staphylococcus aureus have seriously threatened public health. There is an urgent need to propose an existing regimen to overcome multidrug resistance of MRSA. A unique class of novel anti-MRSA thiazolylketenyl quinazolinones (TQs) and their analogs were developed. Some synthesized compounds showed good bacteriostatic potency. Especially TQ 4 was found to exhibit excellent inhibition against MRSA with a low MIC of 0.5 µg/mL, which was 8-fold more effective than norfloxacin. The combination of TQ 4 with cefdinir showed stronger antibacterial potency. Further investigation revealed that TQ 4, with low hemolytic toxicity and low drug resistance, was not only able to inhibit biofilm formation but also could reduce MRSA metabolic activity and showed good drug-likeness. Mechanistic explorations revealed that TQ 4 could cause leakage of proteins by disrupting membrane integrity and block DNA replication by intercalated DNA. Furthermore, the synergistic antibacterial effect with cefdinir might be attributed to TQ 4 with the ability to induce PBP2a allosteric regulation of MRSA and further trigger the opening of the active site to promote the binding of cefdinir to the active site, thus inhibiting the expression of PBP2a, thereby overcoming MRSA resistance and significantly enhancing the anti-MRSA activity of cefdinir. A new strategy provided by these findings was that TQ 4, possessing both excellent anti-MRSA activity and allosteric effect of PBP2a, merited further development as a novel class of antibacterial agents to overcome increasingly severe MRSA infections.

Amoxicillin Versus Other Antibiotic Agents for the Treatment of Acute Otitis Media in Children.

OBJECTIVES: The objective of the study was to compare the antibiotic treatment failure and recurrence rates between antibiotic agents (amoxicillin, amoxicillin-clavulanate, cefdinir, and azithromycin) for children with uncomplicated acute otitis media (AOM). STUDY DESIGN: We completed a retrospective cohort study of children 6 months-12 years of age with uncomplicated AOM identified in a nationwide claims database. The primary exposure was the antibiotic agent, and the primary outcomes were treatment failure and recurrence. Logistic regression was used to estimate ORs, and analyses were stratified by primary exposure, patient age, and antibiotic duration. RESULTS: Among the 1 051 007 children included in the analysis, 56.6% were prescribed amoxicillin, 13.5% were prescribed amoxicillin-clavulanate, 20.6% were prescribed cefdinir, and 9.3% were prescribed azithromycin. Most prescriptions (93%) were for 10 days, and 98% were filled within 1 day of the medical encounter. Treatment failure and recurrence occurred in 2.2% (95% CI: 2.1, 2.2) and 3.3% (3.2, 3.3) of children, respectively. Combined failure and recurrence rates were low for all agents including amoxicillin (1.7%; 1.7, 1.8), amoxicillin-clavulanate (11.3%; 11.1, 11.5), cefdinir (10.0%; 9.8, 10.1), and azithromycin (9.8%; 9.6, 10.0). CONCLUSIONS: Despite microbiologic changes in AOM etiology, treatment failure and recurrence were uncommon for all antibiotic agents and were lower for amoxicillin than for other agents. These findings support the continued use of amoxicillin as a first-line agent for AOM when antibiotics are prescribed.

Assessment of nationally recommended antibiotics for treatment of UTI in U.S.-Mexico border emergency departments.

BACKGROUND: Urinary tract infections (UTIs) seen in the emergency department are commonly treated as an outpatient with oral antibiotics. Given that antibiotics are available for over-the-counter purchase in Mexico, there is speculation that potential misuse and overuse of antibiotics in United States-Mexico border areas could lead to antibiotic resistance patterns that would render some empiric treatments for UTIs less effective. The purpose of this study was to examine the effectiveness of Infectious Disease Society of America (IDSA) guideline-recommended antibiotics for treatment of outpatient UTI diagnosed in the emergency department. Data were collected from a county hospital on the U.S.-Mexico border with a metropolitan area of over 2 million people. Secondary analysis included frequency of urine culture isolated, resistance rates of urine pathogens, and prescriber habits. METHODS: This study was a retrospective chart review of adult patients diagnosed and treated for UTI from August 1, 2019, to February 29, 2020. Culture results of included patients were analyzed against in vitro-tested antibiotics. Bacterial isolate frequency, resistance rates, and prescribing habits were collected. RESULTS: A total of 985 patient charts were reviewed, of which 520 patients met inclusion criteria for analysis of prescribing habits. Of these, 329 positive bacterial culture growths were included in the analysis of antibiotic resistance rates. Oral antibiotics with comparatively lower resistance rates were amoxicillin/clavulanate, cefdinir, cefuroxime, and nitrofurantoin. Oral antibiotics with notably high resistance rates included trimethoprim-sulfamethoxazole (TMP-SMX), tetracycline, ciprofloxacin, levofloxacin, and cephalexin. Nitrofurantoin was prescribed most frequently for outpatient treatment of UTI/cystitis (41.6%) while cephalexin was the most commonly prescribed antibiotic for outpatient treatment of pyelonephritis (50%). CONCLUSION: Our findings suggest that, while part of standard IDSA guidelines, fluoroquinolones and TMP-SMX are not ideal empiric antibiotics for treatment of outpatient UTI in the U.S.-Mexico border region studied due to high resistance rates. Although not listed as first line agents per current IDSA recommendations, 2nd and 3rd generation cephalosporins, and amoxicillin/clavulanate would be acceptable options given resistance patterns demonstrated in accordance with IDSA allowance for tailoring selection to local resistance. Nitrofurantoin appears to be consistent with recommendations and demonstrates a favorable resistance profile for treatment of outpatient UTI within this region.

Influence of Organic Matter on the Sorption of Cefdinir, Memantine and Praziquantel on Different Soil and Sediment Samples.

Pharmaceuticals are known for their great effects and applications in the treatment and suppression of various diseases in human and veterinary medicine. The development and modernization of science and technologies have led to a constant increase in the production and consumption of various classes of pharmaceuticals, so they pose a threat to the environment, which can be subjected to the sorption process on the solid phase. The efficiency of sorption is determined by various parameters, of which the physicochemical properties of the compound and the sorbent are very important. One of these parameters that determine pharmaceutical mobility in soil or sediment is the soil−water partition coefficient normalized to organic carbon (Koc), whose determination was the purpose of this study. The influence of organic matter, suspended in an aqueous solution of pharmaceutical (more precisely: cefdinir, memantine, and praziquantel), was studied for five different types of soil and sediment samples from Croatia. The linear, Freundlich, and Dubinin−Raduskevich sorption isotherms were used to determine specific constants such as the partition coefficient Kd, which directly describes the strength of sorbate and sorbent binding. The linear model proved to be the best with the highest correlation coefficients, R2 > 0.99. For all three pharmaceuticals, a positive correlation between sorption affinity described by Kd and Koc and the amount of organic matter was demonstrated.

Cefdinir-induced red stool and purple discoloration of nutritional formula: A case report.

This case report describes a 4-year-old girl with food aversion who received three separate courses of cefdinir mixed with PediaSure®, an iron-fortified nutritional formula. The patient's stool turned red with variable onset during all three courses of treatment. Moreover, the PediaSure® formula turned purple after mixed with cefdinir, an interaction that has not been previously reported. We recommend that medication counseling for pediatric patients taking cefdinir include a mention of these possible discolorations.

Collaboration with an infection control team promoted appropriate antibiotic use for third molar extraction at a Japanese hospital.

Oral antibiotic therapy is routinely administered when a third molar (M3) is extracted to prevent infectious complications after surgery. Oral third-generation cephalosporins are frequently used after M3 extraction in Japan but at the expense of an increased risk of antimicrobial resistance. Therefore, the infection control team (ICT) at our institution recommended a reduction in use of these agents after M3 extraction. In this study, we compared the types of antibiotic agents prescribed for patients undergoing M3 extraction before and after this recommendation. We investigated the relationship between type of antibiotic used and the likelihood of infectious complications as well as cost savings in patients who underwent M3 extraction in the 6 months before and after the ICT recommendation in July 2018. There was a marked reduction in use of oral third-generation cephalosporins after M3 extraction (P < 0.0001) and increased use of oral penicillins and first-generation cephalosporins after the ICT recommendation. Moreover, surgical site infection (SSIs) were significantly less common after the ICT recommendation (P = 0.0099); however, the SSI rate was higher in patients who received a third-generation cephalosporin than in those who received penicillin (8.8% vs 0.5%). There was also a significant saving in per-patient antibiotic costs after the ICT recommendation (269.5 ± 282.0 JPY vs 454.7 ± 376.6 JPY; P < 0.0001). These findings suggest that collaboration with an ICT promotes appropriate antibiotic use, decreases the risk of an SSI, and improves the cost-benefit ratio in patients undergoing M3 extraction.

Use of oral third generation cephalosporins and quinolones and occurrence of antibiotic-resistant strains in the neurogenic bladder (NB) outpatient setting: a retrospective chart audit.

STUDY DESIGN: A retrospective chart audit. OBJECTIVES: Neurogenic bladder (NB), a risk factor for urinary tract infection, has not been comprehensively studied in terms of antimicrobial stewardship. In this study, we studied the relationship between the use of oral third generation cephalosporins and quinolones, and the occurrence of antibiotic-resistant strains. SETTING: Hyogo Prefectural Central Rehabilitation Hospital, Hyogo, Japan. METHODS: We retrospectively investigated antibiotic-resistant bacteria and the amount of antibiotics prescribed in outpatients with NB caused by spinal cord injury between 2012 and 2017. We intervened in urological departments whose physicians often prescribed third generation cephalosporins and fluoroquinolone, and analyzed the number of prescriptions and the amount of Cefdinir (CFDN) and Levofloxacin (LVFX), and studied changes of ratios in antibiotic-resistant strains such as extended-spectrum ß-lactamases (ESBLs) and quinolone-resistant Escherichia coli and Klebsiella pneumoniae. RESULTS: The number of CFDN prescriptions per year significantly decreased from 463 cases to 130 cases over 6 years (p = 0.012). The number of LVFX prescriptions per year decreased from 640 cases to 171 cases (p = 0.025). The incidence rate of ESBL-producing K. pneumoniae decreased from 25% to 7% of total K. pneumoniae (p < 0.001). The incidence of LVFX-resistant E. coli and K. pneumoniae significantly decreased in 2017 compared with 2012 (p = 0.03 and p = 0.016, respectively). CONCLUSIONS: Antimicrobial stewardship interventions decreased the use of CFDN and LVFX for outpatients with NB. Our findings suggested that the reduction in the use of third generation cephalosporins and quinolones correlates with observed decrease in the occurrence of antibiotic-resistant, ESBL-producing, and quinolone-resistant bacteria.

Pyelonephritis treatment in the community emergency department: Cephalosporins vs. first-line agents.

OBJECTIVE: The purpose of this study was to assess treatment with a fluoroquinolone or trimethoprim-sulfamethoxazole versus cephalosporins for pyelonephritis in discharged patients from a community hospital setting. METHODS: A retrospective chart review was completed for adult female patients who received a prescription for a cephalosporin, fluoroquinolone or trimethoprim-sulfamethoxazole for the treatment of pyelonephritis within the network of a large healthcare system. The primary endpoint evaluated the failure rate of each treatment group. The secondary endpoint evaluated the difference between rates of resistance on culture and sensitivity reports for treatment groups. RESULTS: A total of 55 patients in the cephalosporin group and 43 patients in the fluoroquinolone and trimethoprim-sulfamethoxazole group were reviewed. The primary endpoint occurred in 0% of the patients in the cephalosporin group and in 23% of the patients in the fluoroquinolone and trimethoprim-sulfamethoxazole group, p < 0.001. Of the 98 urine samples collected, 71 samples were positive for pathogen growth. Upon evaluation of these isolates, 6% were resistant to cephalexin, 1% was resistant to cefdinir, 3% were resistant to ciprofloxacin and 23% were resistant to trimethoprim-sulfamethoxazole. Trimethoprim-sulfamethoxazole showed statistical significance for more bacterial resistance compared to the other agents, p < 0.01. CONCLUSION: Failure of therapy for pyelonephritis occurred more often in the fluoroquinolone and trimethoprim-sulfamethoxazole group than in the cephalosporin group. The findings in this study are most applicable to patients who are treated on an outpatient basis. A prospective, randomized clinical trial is necessary to confirm these results.

Antibiotics-First Versus Surgery for Appendicitis: A US Pilot Randomized Controlled Trial Allowing Outpatient Antibiotic Management.

STUDY OBJECTIVE: Randomized trials suggest that nonoperative treatment of uncomplicated appendicitis with antibiotics-first is safe. No trial has evaluated outpatient treatment and no US randomized trial has been conducted, to our knowledge. This pilot study assessed feasibility of a multicenter US study comparing antibiotics-first, including outpatient management, with appendectomy. METHODS: Patients aged 5 years or older with uncomplicated appendicitis at 1 US hospital were randomized to appendectomy or intravenous ertapenem greater than or equal to 48 hours and oral cefdinir and metronidazole. Stable antibiotics-first-treated participants older than 13 years could be discharged after greater than or equal to 6-hour emergency department (ED) observation with next-day follow-up. Outcomes included 1-month major complication rate (primary) and hospital duration, pain, disability, quality of life, and hospital charges, and antibiotics-first appendectomy rate. RESULTS: Of 48 eligible patients, 30 (62.5%) consented, of whom 16 (53.3%) were randomized to antibiotics-first and 14 (46.7%) to appendectomy. Median age was 33 years (range 9 to 73 years), median WBC count was 15,000/µL (range 6,200 to 23,100/µL), and median computed tomography appendiceal diameter was 10 mm (range 7 to 18 mm). Of 15 antibiotic-treated adults, 14 (93.3%) were discharged from the ED and all had symptom resolution. At 1 month, major complications occurred in 2 appendectomy participants (14.3%; 95% confidence interval [CI] 1.8% to 42.8%) and 1 antibiotics-first participant (6.3%; 95% CI 0.2% to 30.2%). Antibiotics-first participants had less total hospital time than appendectomy participants, 16.2 versus 42.1 hours, respectively. Antibiotics-first-treated participants had less pain and disability. During median 12-month follow-up, 2 of 15 antibiotics-first-treated participants (13.3%; 95% CI 3.7% to 37.9%) developed appendicitis and 1 was treated successfully with antibiotics; 1 had appendectomy. No more major complications occurred in either group. CONCLUSION: A multicenter US trial comparing antibiotics-first to appendectomy, including outpatient management, is feasible to evaluate efficacy and safety.

Cefdinir Solid Dispersion Composed of Hydrophilic Polymers with Enhanced Solubility, Dissolution, and Bioavailability in Rats.

The aim of this work was to develop cefdinir solid dispersions (CSDs) prepared using hydrophilic polymers with enhanced dissolution/solubility and in vivo oral bioavailability. CSDs were prepared with hydrophilic polymers such as hydroxypropyl-methylcellulose (HPMC; CSD1), carboxymethylcellulose-Na (CMC-Na; CSD2), polyvinyl pyrrolidone K30 (PVP K30; CSD3) at the weight ratio of 1:1 (drug:polymer) using a spray-drying method. The prepared CSDs were characterized by aqueous solubility, differential scanning calorimetry (DSC), powder X-ray diffraction (p-XRD), scanning electron microscopy (SEM), aqueous viscosity, and dissolution test in various media. The oral bioavailability of CSDs was also evaluated in rats and compared with cefdinir powder suspension. The cefdinir in CSDs was amorphous form, as confirmed in the DSC and p-XRD measurements. The developed CSDs commonly resulted in about 9.0-fold higher solubility of cefdinir and a significantly improved dissolution profile in water and at pH 1.2, compared with cefdinir crystalline powder. Importantly, the in vivo oral absorption (represented as AUCinf) was markedly increased by 4.30-, 6.77- and 3.01-fold for CSD1, CSD2, and CSD3, respectively, compared with cefdinir suspension in rats. The CSD2 prepared with CMC-Na would provide a promising vehicle to enhance dissolution and bioavailability of cefdinir in vivo.

INVASIVE SALMONELLOSIS PRESENTING AS A LUNG ABSCESS: A CASE REPORT.

Salmonella spp are an uncommon cause of lung abscess. A 59 year old man presented to our hospital with a 1 month history of cough and low grade fever progressing to high grade fever for 1 week. He had a past medical history significant for diabetes mellitus type 2 and focal segmental glomerulosclerosis for which he was receiving prednisolone, initially at 60 mg daily tapering to 20 mg daily. On presentation he was febrile and had decreased breath sounds and dullness to percussion over the right lower lung field. A chest X-ray showed a cavitary lesion with an air-fluid level in the right lung. Computed tomography of the lung revealed 2 cavitary lesions in the right upper and lower lungs. Sputum culture revealed Salmonella spp group B. He was treated successfully with ceftriaxone intravenously for 1 month followed by oral cefdinir. A chest X-ray at 1 month showed significant improvement; he was treated conservatively without surgical drainage. Salmonella can cause lung abscesses, especially in the immune suppressed.

Combining the FtsZ-Targeting Prodrug TXA709 and the Cephalosporin Cefdinir Confers Synergy and Reduces the Frequency of Resistance in Methicillin-Resistant Staphylococcus aureus.

Combination therapy of bacterial infections with synergistic drug partners offers distinct advantages over monotherapy. Among these advantages are (i) a reduction of the drug dose required for efficacy, (ii) a reduced potential for drug-induced toxicity, and (iii) a reduced potential for the emergence of resistance. Here, we describe the synergistic actions of the third-generation oral cephalosporin cefdinir and TXA709, a new, FtsZ-targeting prodrug that we have developed with improved pharmacokinetics and enhanced in vivo efficacy against methicillin-resistant Staphylococcus aureus (MRSA) relative to earlier agents. We show that the active product of TXA709 (TXA707) acts synergistically with cefdinir in vitro against clinical isolates of MRSA, vancomycin-intermediate S. aureus (VISA), vancomycin-resistant S. aureus (VRSA), and linezolid-resistant S. aureus (LRSA). In addition, relative to TXA707 alone, the combination of TXA707 and cefdinir significantly reduces or eliminates the detectable emergence of resistance. We also demonstrate synergy in vivo with oral administration of the prodrug TXA709 and cefdinir in mouse models of both systemic and tissue (thigh) infections with MRSA. This synergy reduces the dose of TXA709 required for efficacy 3-fold. Viewed as a whole, our results highlight the potential of TXA709 and cefdinir as a promising combination for the treatment of drug-resistant staphylococcal infections.

Antibiotics as part of the management of severe acute malnutrition.

BACKGROUND: Severe acute malnutrition contributes to 1 million deaths among children annually. Adding routine antibiotic agents to nutritional therapy may increase recovery rates and decrease mortality among children with severe acute malnutrition treated in the community. METHODS: In this randomized, double-blind, placebo-controlled trial, we randomly assigned Malawian children, 6 to 59 months of age, with severe acute malnutrition to receive amoxicillin, cefdinir, or placebo for 7 days in addition to ready-to-use therapeutic food for the outpatient treatment of uncomplicated severe acute malnutrition. The primary outcomes were the rate of nutritional recovery and the mortality rate. RESULTS: A total of 2767 children with severe acute malnutrition were enrolled. In the amoxicillin, cefdinir, and placebo groups, 88.7%, 90.9%, and 85.1% of the children recovered, respectively (relative risk of treatment failure with placebo vs. amoxicillin, 1.32; 95% confidence interval [CI], 1.04 to 1.68; relative risk with placebo vs. cefdinir, 1.64; 95% CI, 1.27 to 2.11). The mortality rates for the three groups were 4.8%, 4.1%, and 7.4%, respectively (relative risk of death with placebo vs. amoxicillin, 1.55; 95% CI, 1.07 to 2.24; relative risk with placebo vs. cefdinir, 1.80; 95% CI, 1.22 to 2.64). Among children who recovered, the rate of weight gain was increased among those who received antibiotics. No interaction between type of severe acute malnutrition and intervention group was observed for either the rate of nutritional recovery or the mortality rate. CONCLUSIONS: The addition of antibiotics to therapeutic regimens for uncomplicated severe acute malnutrition was associated with a significant improvement in recovery and mortality rates. (Funded by the Hickey Family Foundation and others; ClinicalTrials.gov number, NCT01000298.).

Application and optimization of organic-inorganic hybrid monolithic capillary electrochromatography for in vivo cefdinir determination with microdialysis.

In this study, an organic-inorganic hybrid monolithic capillary column was applied and optimized for the determination of cefdinir in plasma, and the electro-osmotic flow that usually hinders migration in reverse polarity became a driving force. The Sample used for pharmacokinetic research was collected by microdialysis using phosphate buffer (pH 7.4) as perfusate, and a volume of 60 µL fluid was mixed with 140 µL of acetonitrile. By using a silica-allyldimethyldodecylammonium monolithic column (100 µm inner diameter, 21 cm effective length and 31.2 cm total length), and a mobile phase consisting of phosphate and acetonitrile (pH 4.5, 50:50, v/v), at a voltage of 20 kV, the analytes were successfully separated with the background within 2.5 min. The detection wavelength was 214 nm. The calibration curve showed a good linearity (r(2) = 0.9994) over the concentration range of 0.2-50 µg/mL. The proposed method showed good specificity, linearity, sensitivity, precision and recovery, and the introduction of field amplified sample stacking helped to improve the low recovery caused by microdialysis. This method was successfully applied to quantify cefdinir in rat plasma to support a pre-clinical pharmacokinetic trial.