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

Background: Quantitative estimates of collateral resistance induced by antibiotic use are scarce. This study compared the effects of treatment with amoxicillin/clavulanate or cefazolin, compared to cefuroxime, on future resistance to ceftazidime among hospitalized patients. Methods: A retrospective analysis of patients with positive bacterial cultures hospitalized in an Israeli hospital during 2016-2019 was conducted. Patients were restricted to those treated with either amoxicillin/clavulanate, cefazolin, or cefuroxime and re-hospitalized with a positive bacterial culture during the following year. A 1:1 matching was performed for each patient in the amoxicillin/clavulanate and cefazolin groups, to a single patient from the cefuroxime group, yielding 185:185 and 298:298 matched patients. Logistic regression and g-formula (standardization) were used to estimate the odds ratio (OR), risk difference (RD), and number needed to harm (NNH). Results: Cefuroxime induced significantly higher resistance to ceftazidime than amoxicillin/clavulanate or cefazolin: the marginal OR was 1.76) 95%CI 1.16-2.83) compared to amoxicillin/clavulanate, and 1.98 (95%CI 1.41- 2.8) compared to cefazolin; The RD was 0.118 (95%CI 0.031-0.215) compared to amoxicillin/clavulanate, and 0.131 (95%CI 0.058-0.197) compared to cefazolin. We also estimated the NNH: replacing amoxicillin/clavulanate or cefazolin with cefuroxime would yield ceftazidime-resistance in one more patient for every 8.5 (95% CI 4.66-32.14) or 7.6 (95% CI 5.1-17.3) patients re-hospitalized in the following year. Conclusions: Our results indicate that treatment with amoxicillin/clavulanate or cefazolin is preferable to cefuroxime, in terms of future collateral resistance. The results presented here are a first step towards quantitative estimations of the ecological damage caused by different antibiotics.

Impact of a pilot multimodal intervention to decrease antibiotic use for respiratory infections in a geriatric clinic

Background: More than 80% of antibiotics are prescribed in the outpatient setting, of which 30% are inappropriate. The National Action Plan for Combating Antimicrobial Resistance called for a 50% decrease in outpatient antibiotic use by 2020. Inappropriate antibiotics are associated with adverse reactions and Clostridioides difficile infection, especially among older adults. Study design: Before and after study. Methods: We performed a quality improvement initiative at the University of Colorado Seniors Clinic. Providers received education on antibiotic guidelines, electronic antibiotic order sets were introduced with standardized stop dates. Antibiotic use data were collected for 6 months before and 6 months after the intervention, from December to May to avoid seasonal variation. Descriptive statistics and linear mixed-effects regression models were used for this comparison. Results: Total antibiotic prescriptions for acute respiratory conditions decreased from 137 prescriptions before the intervention (December 1, 2017, to May 31, 2018) to 112 prescriptions after the intervention (December 1, 2018, to May 31, 2019), driven primarily by decreases in antibiotic prescriptions for pneumonia, sinusitis, and bronchitis. Prescriptions for broad-spectrum antibiotics declined following the intervention including decreases in levofloxacin from 12 (9%) to 3 (3%) and amoxicillin-clavulanate from 15 (12%) to 7 (7%). We detected significant reductions in prescribed antibiotic durations (days) after the intervention for sinusitis (estimate, −2.0; 95% CI, −3.1 to −1.0; P = .0003), pharyngitis (estimate, −2.5; 95% CI, −4.6 to −0.5; P = .018), and otitis (−3.2; 95% CI, −5.2 to −1.3; P = .008). Conclusions: Low-cost interventions were initially successful in changing patterns of antibiotic use and decreasing overall antibiotic prescribing among older patients in the outpatient setting. Long-term follow-up studies are needed to determine the sustainability and clinical impact of these interventions.

Antimicrobial Resistance, Serologic and Molecular Characterization of E. coli Isolated from Calves with Severe or Fatal Enteritis in Bavaria, Germany

Worldwide, enterotoxigenic Escherichia coli (ETEC) cause neonatal diarrhea and high mortality rates in newborn calves, leading to great economic losses. In Bavaria, Germany, no recent facts are available regarding the prevalence of virulence factors or antimicrobial resistance of ETEC in calves. Antimicrobial susceptibility of 8713 E. coli isolates obtained from 7358 samples of diseased or deceased diarrheic calves were investigated between 2015 to 2019. Considerably high rates of 84.2% multidrug-resistant and 15.8% extensively drug-resistant isolates were detected. The resistance situation of the first, second and third line antimicrobials for the treatment, here amoxicillin-clavulanate, enrofloxacin and trimethoprim-sulfamethoxazole, is currently acceptable with mean non-susceptibility rates of 28.1%, 37.9% and 50.0% over the investigated 5-year period. Furthermore, the ETEC serotypes O101:K28, O9:K35, O101:K30, O101:K32, O78:K80, O139:K82, O8:K87, O141:K85 and O147:K89, as well as the virulence factors F17, F41, F5, ST-I and stx1 were identified in a subset of samples collected in 2019 and 2020. The substantially high rates of multi- and extensively drug-resistant isolates underline the necessity of continuous monitoring regarding antimicrobial resistance to provide reliable prognoses and adjust recommendations for the treatment of bacterial infections in animals.

The Darkest Place Is under the Candlestick-Healthy Urogenital Tract as a Source of Worldwide Disseminated Extraintestinal Pathogenic Escherichia coli Lineages

Since the discovery of the urinary microbiome, including the identification of Escherichia coli in healthy hosts, its involvement in UTI development has been a subject of high interest. We explored the population diversity and antimicrobial resistance of E. coli (n = 22) in the urogenital microbiome of ten asymptomatic women (representing 50% of the sample tested). We evaluated their genomic relationship with extraintestinal pathogenic E. coli (ExPEC) strains from healthy and diseased hosts, including the ST131 lineage. E. coli prevalence was higher in vaginal samples than in urine samples, and occasionally different lineages were observed in the same individual. Furthermore, B2 was the most frequent phylogenetic group, with the most strains classified as ExPEC. Resistance to antibiotics of therapeutic relevance (e.g., amoxicillin-clavulanate conferred by blaTEM-30) was observed in ExPEC widespread lineages sequence types (ST) 127, ST131, and ST73 and ST95 clonal complexes. Phylogenomics of ST131 and other ExPEC lineages revealed close relatedness with strains from gastrointestinal tract and diseased host. These findings demonstrate that healthy urogenital microbiome is a source of potentially pathogenic and antibiotic resistant E. coli strains, including those causing UTI, e.g., ST131. Importantly, diverse E. coli lineages can be observed per individual and urogenital sample type which is relevant for future studies screening for this uropathogen.

Prescription Pattern of Antimicrobial Agents in Various Dental Clinics at Malabar Region of Kerala, South India

Antimicrobial agents (AMAs) are among the most commonly prescribed drugs in dental practice. However inappropriate prescribing and irrational use of antimicrobial agents without prior culture and sensitivity tests, inadequate duration, dosing etc. have been identified as major factors contributing to the emergence of antibiotic resistance, which is an ongoing challenge in all over the world. A total of 1900 patients were screened and out of which 1748 patients were selected based on the inclusion and exclusion criteria for the study after taking consent. This study shows that the majority of patients attended in these clinics were female, 1020 (58.35%) and majority of patients (717) comes under age group 21-40 (41.02%) followed by age group by ≤ 20 (32.43%). This study established that most commonly recommended antimicrobial agents were amoxicillin, followed by amoxicillin-clavulanate and metronidazole. The antimicrobial agents like Ciprofloxacin, Cefixime, Tetracyclines, Azithromycines were also used but in less extent. This study also revealed that the selection of antimicrobials was not confirmed with culture and sensitivity tests in all cases, which may negatively influence bacterial resistance profile.

High prevalence of OXA-23 carbapenemase-producing Proteus mirabilis among amoxicillin-clavulanate resistant isolates in France

In this multicentric study performed in 12 French hospitals, we reported that 26.9% (14/52) of the amoxicillin/clavulanate-resistant Proteus mirabilis isolates produced the OXA-23 carbapenemase. We found that inhibition zone diameter less than 11 mm around amoxicillin/clavulanate disc was an accurate screening cut-off to detect these OXA-23 producers. We confirmed by whole genome sequencing that these OXA-23-producers all belonged to the same lineage that has been demonstrated to disseminate OXA-23 or OXA-58 in P. mirabilis .

Pattern of Antibiotic Prescription for Orofacial Infections among Dentists: A Narrative Review of Literature

Bacterial infections are common in dental and oral clinical practice. It is been estimated that about 10% of total antibiotic prescriptions are related to dental infections. Combination of amoxicillin-clavulanate and plain amoxycillin is the most commonly used drug by dentists across the world. Three general considerations were recognized in this literature review—Empirical antibiotic prescription by dentists without a culture test; concomitant prescription of antibiotics with non-steroidal anti-inflammatory drugs which may ultimately affect the bioavailability of the former drug; and the increased antimicrobial resistance amongst oral pathogens. Since decades, antibiotics have been prescribed for the treatment of odontogenic infections and non-odontogenic oral infections, and for focal infections and sepsis prophylaxis. Renal failure, liver failure, and pregnancy are situations that require special attention when considering an antibiotic prescription. This review attempted to contribute to the rational use and abuse of antibiotics while focusing on the general characteristics of these drugs.

Overview on the Causes and Updated Management of Impetigo

Impetigo is the most common bacterial skin infection in children between the ages of 2 and 5. There are two main types: non-vesicular (70% of cases) and bullous (30% of cases). Non-bullous impetigo or impetigo is caused by Staphylococcus aureus or Streptococcus pyogenes and is characterized by honey-colored skin on the face and limbs. Impetigo primarily affects the skin or is a secondary infection with insect bites, eczema, or herpes lesions. Bullous impetigo caused only by S. aureus causes large, relaxed blisters and is more likely to affect the interstitial area. Both types usually resolve within a few weeks without scarring, and complications are rare, the most serious of which is streptococcal glomerulonephritis. Treatment includes topical antibiotics such as mupirocin, retapamulin, and fusidic acid. Oral antibiotic therapy can be used for impetigo with large blisters, or when topical therapy is not practical. Amoxicillin / clavulanate, dicloxacillin, cephalexin, clindamycin, doxicillin, minocycline, trimetoprim / sulfamethoxazole, and macrolides are optional, but penicillin is not.

β-Lactam Resistance in Upper Respiratory Tract Pathogens Isolated from a Tertiary Hospital in Malaysia

The rise of antimicrobial resistance (AMR) among clinically important bacteria, including respiratory pathogens, is a growing concern for public health worldwide. Common causative bacteria for upper respiratory tract infections (URTIs) include Streptococcus pneumoniae and Haemophilus influenzae, and sometimes Staphylococcus aureus. We assessed the β-lactam resistant trends and mechanisms of 150 URTI strains isolated in a tertiary care hospital in Kuala Lumpur Malaysia. High rates of non-susceptibility to penicillin G (38%), amoxicillin-clavulanate (48%), imipenem (60%), and meropenem (56%) were observed in S. pneumoniae. Frequent mutations at STMK and SRNVP motifs in PBP1a (41%), SSNT motif in PBP2b (32%), and STMK and LKSG motifs in PBP2x (41%) were observed in S. pneumoniae. H. influenzae remained highly susceptible to most β-lactams, except for ampicillin. Approximately half of the ampicillin non-susceptible H. influenzae harboured PBP3 mutations (56%) and only blaTEM was detected in the ampicillin-resistant strains (47%). Methicillin-susceptible S. aureus (MSSA) strains were mostly resistant to penicillin G (92%), with at least two-fold higher median minimum inhibitory concentrations (MIC) for all penicillin antibiotics (except ticarcillin) compared to S. pneumoniae and H. influenzae. Almost all URTI strains (88–100%) were susceptible to cefcapene and flomoxef. Overall, β-lactam antibiotics except penicillins remained largely effective against URTI pathogens in this region.

Ceftazidime induced liver injury

A 65-year-old woman with type II diabetes mellitus complicated by non-healing ulcers with recurrent osteomyelitis was admitted for progression of cellulitis after treatment failure with an outpatient course of amoxicillin-clavulanate. She was found to have persistent osteomyelitis and started on ceftazidime for a culture documented Pseudomonas aeruginosa infection. After two parenteral doses, she had a rapid rise in liver function tests (LFTs) in a hepatocellular pattern. Due to rapid identification, all medications with potential hepatotoxicity, including ceftazidime, were discontinued and the LFTs promptly returned to baseline over 3 days. Of note, the patient did not experience any symptoms of liver injury. Other causes of acute liver injury were effectively ruled out, but the case was confounded by usage of other potential hepatotoxic medications. Still, the most likely culprit was ceftazidime, a rare cause of drug induced liver injury with very few reports in the literature.