Oral Amoxicillin-clavulanic Acid Research Articles

6472 Methimazole Induced Agranulocytosis: Uncommon Complication of a Common Medication

Abstract Disclosure: R. Kaur: None. L. Kaur: None. A. Sridhar: None. T. Chaudhary: None. N. Patel: None. Methimazole (MMI) induced agranulocytosis is a rare and life threatening adverse effect that usually occurs within 3 months of drug initiation and can rapidly lead to overwhelming infection. It is reported in 0.1 to 0.5 % of patients on treatment with methimazole. MMI is a standard drug used in graves disease and toxic multinodular goiter. We report a case of MMI induced agranulocytosis in an elderly female with recently diagnosed toxic multinodular goiter. A 66 year old female with past medical history of recently diagnosed toxic multinodular goiter for which she was started on methimazole 80mg/day two months ago presented to the emergency department with chief complaint of severe sore throat associated with rapidly increasing pharyngeal pain and fever over the past 24 hours. She was lethargic, febrile with temperature of 102 F, tachycardic with heart rate of 115/minute and hypotensive with blood pressure of 108/64 mm Hg. Physical examination revealed diffuse pharyngeal and tonsillar erythema with bilateral purulent exudate with tender anterior cervical lymphadenopathy. Thyroid was enlarged, firm, irregular and nontender. Pulmonary, cardiac and abdominal exam was unremarkable. Lab work showed severe leukopenia with WBC count of 1,600/mm3, neutropenia with absolute neutrophil count of 0.0 x 1000/ul (normal range 1.8-7.3 x 1000/ul) and erythrocyte sedimentation rate and C reactive protein were both elevated. Blood cultures and fungal cultures showed no growth. Urinalysis and urine culture were both unremarkable. She had an extensive haematological, rheumatological and infectious disease workup for neutropenia, which was largely unrevealing. Rapid streptococcal testing was negative but throat cultures grew beta haemolytic streptococci. Treatment included suspending methimazole, administering antimicrobial therapy with piperacillin - tazobactam, acyclovir and fluconazole. She was also started on a granulocyte colony stimulating factor. Patient presented satisfactory evolution with progressive increase in leukocyte count and remission of symptoms by day 5 of treatment, rendering further bone marrow testing unnecessary. Antibiotics were changed to oral amoxicillin-clavulanic acid after throat culture results were available and the patient was discharged in stable condition. One month after discharge she underwent total thyroidectomy for definitive cure and is currently followed up as an outpatient by endocrinology. The objective of this case report is to present an uncommon case of agranulocytosis secondary to use of methimazole and to increase awareness among the physicians about the need to consider this diagnosis in patients on this medication. It is also advised that these patients be educated about the drugs side effects, a practice that may avert suffering and unnecessary costs. Presentation: 6/3/2024

Effectiveness of Oral Cephalexin-Clavulanic Acid, Cefuroxime, and Amoxicillin-Clavulanic Acid in the Management of Dental Infections: A Real-World, Retrospective, Electronic Medical Record-Based Study in India.

Despite multiple antibiotics being available to manage dental infections (DI), there is lack of data comparing commonly prescribed antibiotics in India. The aim of this study was to evaluate the real-world effectiveness and tolerability of cephalexin-clavulanic acid fixed-dose combination (cephalexin CV FDC) in contrast with amoxicillin-clavulanic acid (co-amoxiclav FDC) and cefuroxime among patients with dental infections (odontogenic) in India. This retrospective, multi-centric, observational, real-world electronic medical record (EMR)-based study was conducted between January 2022 and December 2022. The EMRs of 355 adults with DI receiving oral cephalexin CV, co-amoxiclav, or cefuroxime were categorized into two distinct groups: Group I (Test Group) with patients prescribed cephalexin extended release 375/750mg along with clavulanic acid 125mg; and Group II (Comparator Group) with patients prescribed co-amoxiclav 625mg (500mg amoxicillin + 125mg clavulanic acid) or cefuroxime (250mg/500mg). Toothache was the most common complaint, reported by 95.5% of patients, followed by swelling (46.8%), tooth sensitivity (35.5%), pus discharge (33.0%), redness and halitosis (30.4% each). Dental caries was observed in 81.1% of patients. Clinical improvement, defined as improvement/partial resolution of infection-related clinical signs and symptoms (composite measure of pain, swelling, fever, requirement of additional antimicrobial therapy) as per dentists' judgment, was recorded in 98.3% of patients with cephalexin CV, 96.8% of patients with co-amoxiclav, and 98.9% of patients treated with cefuroxime within 10days. Time (days) to clinical improvement was numerically lesser among patients receiving cephalexin CV (4.6± 2.0) compared with cefuroxime (4.9± 2.1) and co-amoxiclav (5.0± 2.6). All treatments were well tolerated. Cephalexin CV was as effective as co-amoxiclav and cefuroxime, with faster clinical improvement and better resolution of certain symptoms.

Acute management of pneumonia in adult patients.

Acute management of pneumonia in adult patients.

Efficacy and safety of switching from intravenous to oral antibiotics (amoxicillin–clavulanic acid) versus a full course of intravenous antibiotics in neonates with probable bacterial infection (RAIN): a multicentre, randomised, open-label, non-inferiority trial

Switching from intravenous antibiotic therapy to oral antibiotic therapy among neonates is not yet practised in high-income settings due to uncertainties about exposure and safety. We aimed to assess the efficacy and safety of early intravenous-to-oral antibiotic switch therapy compared with a full course of intravenous antibiotics among neonates with probable bacterial infection. In this multicentre, randomised, open-label, non-inferiority trial, patients were recruited at 17 hospitals in the Netherlands. Neonates (postmenstrual age ≥35 weeks, postnatal age 0-28 days, bodyweight ≥2 kg) in whom prolonged antibiotic treatment was indicated because of a probable bacterial infection, were randomly assigned (1:1) to switch to an oral suspension of amoxicillin 75 mg/kg plus clavulanic acid 18·75 mg/kg (in a 4:1 dosing ratio, given daily in three doses) or continue on intravenous antibiotics (according to the local protocol). Both groups were treated for 7 days. The primary outcome was cumulative bacterial reinfection rate 28 days after treatment completion. A margin of 3% was deemed to indicate non-inferiority, thus if the reinfection rate in the oral amoxicillin-clavulanic acid group was less than 3% higher than that in the intravenous antibiotic group the null hypothesis would be rejected. The primary outcome was assessed in the intention-to-treat population (ie, all patients who were randomly assigned and completed the final follow-up visit on day 35) and the per protocol population. Safety was analysed in all patients who received at least one administration of the allocated treatment and who completed at least one follow-up visit. Secondary outcomes included clinical deterioration and duration of hospitalisation. This trial was registered with ClinicalTrials.gov, NCT03247920, and EudraCT, 2016-004447-36. Between Feb 8, 2018 and May 12, 2021, 510 neonates were randomly assigned (n=255 oral amoxicillin-clavulanic group; n=255 intravenous antibiotic group). After excluding those who withdrew consent (n=4), did not fulfil inclusion criteria (n=1), and lost to follow-up (n=1), 252 neonates in each group were included in the intention-to-treat population. The cumulative reinfection rate at day 28 was similar between groups (one [<1%] of 252 neonates in the amoxicillin-clavulanic acid group vs one [<1%] of 252 neonates in the intravenous antibiotics group; between-group difference 0 [95% CI -1·9 to 1·9]; pnon-inferiority<0·0001). No statistically significant differences were observed in reported adverse events (127 [50%] vs 113 [45%]; p=0·247). In the intention-to-treat population, median duration of hospitalisation was significantly shorter in the amoxicillin-clavulanic acid group than the intravenous antibiotics group (3·4 days [95% CI 3·0-4·1] vs 6·8 days [6·5-7·0]; p<0·0001). An early intravenous-to-oral antibiotic switch with amoxicillin-clavulanic acid is non-inferior to a full course of intravenous antibiotics in neonates with probable bacterial infection and is not associated with an increased incidence of adverse events. The Netherlands Organization for Health Research and Development, Innovatiefonds Zorgverzekeraars, and the Sophia Foundation for Scientific Research.

Assessing the Variability of Antibiotic Management in Patients With Open Hand Fractures Presenting to the Pediatric Emergency Department.

Open hand fractures may be difficult to recognize and treat. There is variability in management and administration of antibiotics for these types of injuries. Unlike open long bone fractures, there is no standardized protocol for antibiotic administration for open hand fractures in children. The objective of this study is to assess the variability of antibiotic management of open hand fractures in children. We performed a retrospective chart review at a tertiary hospital in New York of patients with hand injuries between ages 0 and 18 years presenting to the emergency department during January 2019 and December 2020. Patient encounters were reviewed for open fractures of the hand. Descriptive statistics were included for demographic and physical characteristics. There were 80 encounters with open hand fractures, of which the most common being tuft fractures (77.5%). The mean age was 7.6 years (SD, 4.7 years) with male predominance (58.8%). Crush injuries were the most common mechanism of injury (78.8%). Bedside repair was performed on 62 encounters (77.5%), of which 45 (72.5%) required nail bed repair, 56 (90.3%) required suturing, and 24 (38.7%) required reduction. Antibiotics were given to 62 (77.5%) encounters, most commonly oral cefalexin (45.2%), oral amoxicillin-clavulanic acid (27.4%), and intravenous cefazolin (14.5%). Median time to antibiotics from emergency department registration to administration was 150 minutes (interquartile range, 92-216 minutes). Antibiotic prescriptions were sent for 71 encounters (88.8%). Seventy seven (96.3%) of the encounters were discharged home. Pediatric open hand fractures have a variability of type and timing to antibiotics. Future initiatives should attempt to create standardized guidelines for management of open hand fractures.

Amoxicillin plus Clavulanic Acid Vs Amoxicillin in the Treatment of Community Acquired Pneumonia in Children: A Double-Blind, Randomized, Controlled Trial

WHO recommendations for the management of Community Acquired Pneumonia (CAP) have been revised since 2014, amoxicillin is recommended as first choice for oral antibiotic therapy in domiciliary treatment of children. This study was planned to compare cure rate of oral amoxicillin plus clavulanic acid vs oral amoxicillin in children with CAP. Children aged 6- 36 mo, presenting with the clinical features consistent with the diagnosis of CAP were enrolled. Patients were given oral amoxicillin or amoxycillin plus clavulanic acid for 5 d and followed at 48h, 5th d and 2 mo. The cure rate, adverse reactions and recurrence were assessed and analysed for these two drugs. The cure rate of CAP in amoxicillin plus clavulanic acid group was significantly higher as compared to amoxicillin group (93.88% vs 79.17%, p 0.013). The chances of cure rate increased by 15.3% for children receiving oral amoxicillin plus clavulanic acid. Only mild side effects like diarrhea (22.1%), nausea (9.6%), vomiting (5.7%), and maculo-papular rash (2.9%) were observed in both the groups. All the cured children were followed up to 2 mo and none had recurrence of symptoms.

BRONCHOPLEURAL FISTULA COMPLICATION OF INTRAPLEURAL TPA/DORNASE IN PRESENCE OF LUNG ABSCESS

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: A short course intrapleural instillation of tissue plasminogen activator (tPA) and recombinant human deoxyribonuclease I (dornase alfa) is a highly safe and effective treatment for complicated parapneumonic effusions (CPE) and empyema. It improves drainage and reduces surgical referral as well as hospitalization length [1-3]. Clinical experiences of dual tPA/dornase therapy and ensuing rare complications are cumulating. CASE PRESENTATION: A 49 year old female with past medical history of hypertension, extensive tobacco use, and history of IV drug use presented with complaints of right sided chest pain, productive cough with blood tinged sputum, and weight loss for 2 weeks. Vitals were normal and physical exam only significant for decreased right chest breath sounds. An initial CT chest demonstrated right sided pleural effusion with air-fluid level and a cavitary lesion of 7 cm suggestive of lung abscess. She was admitted to the medical floor with antibiotics. On day 2, a 10F pigtail catheter was placed with frank pus evacuated. Pleural fluid analysis showed WBC >800K cells/μL, glucose 10 mg/dL, LDH >40K IU/L, protein 3.1 gm/dL. The cultures of the pleural fluid grew Streptococcus intermedius. Repeat CT demonstrated chest tube in position without communication between empyema and lung abscess.On day 4, two rounds of intrapleural 10mg tPA and 5mg dornase alfa were administered to facilitate drainage. The next day, an additional 250 mL of bloody output was noted from the pigtail catheter with development of a new air leak. A repeat CT chest revealed improvement in the right sided empyema and subcutaneous emphysema. The visualization of previously described cavitary lesion was noted to be open to the pleural cavity.She was transferred to the ICU for close observation and management due to development of a bronchopleural fistula (BPF). A larger 16F chest tube was placed to aid drainage and reduce subcutaneous emphysema. After 2 days, the patient was no longer experiencing air leak and subsequently had chest tube removed on hospital day 7. She was discharged home with an extended course of oral amoxicillin-clavulanic acid and to follow-up in clinic. DISCUSSION: This case describes a complication that can happen when using intrapleural tpa/dornase therapy in presence of lung abscess which can lead to BPF which can result from abscess rupture into the pleural cavity. As for our literature review, we could not find any reported cases of similar complications of fistula development, however, it was noted bleeding complication with prolonged tpa/dornase use. CONCLUSIONS: Standard 3 day treatment is effective in reducing surgical referral and intervention, however, it is important to appreciate complications that can arise from therapy in presence of lung abscesses. There should close monitoring of chest tube output upon utilization of tpa/dornase therapy. REFERENCE #1: Rahman, N.M., et al., Intrapleural use of tissue plasminogen activator and DNase in pleural infection. N Engl J Med, 2011. 365(6): p. 518-26. REFERENCE #2: Majid, A., et al., Concurrent Intrapleural Instillation of Tissue Plasminogen Activator and DNase for Pleural Infection. A Single-Center Experience. Ann Am Thorac Soc, 2016. 13(9): p. 1512-8. REFERENCE #3: Piccolo, F., et al., Intrapleural tissue plasminogen activator and deoxyribonuclease therapy for pleural infection. J Thorac Dis, 2015. 7(6): p. 999-1008. DISCLOSURES: No relevant relationships by Mohammed Al-Ourani, source=Web Response No relevant relationships by Rami Batarseh, source=Web Response No relevant relationships by Belete Desimmie, source=Web Response No relevant relationships by Anup Kumar, source=Web Response No relevant relationships by Kelsey Marshall, source=Web Response

Topical versus systemic antibiotics for chronic suppurative otitis media.

Topical versus systemic antibiotics for chronic suppurative otitis media.

Synergistic interactions of ionic liquids and antimicrobials improve drug efficacy.

SummaryCombinations of ionic liquids (ILs) with antimicrobial compounds have been shown to produce synergistic activities in model liposomes. In this study, imidazolium chloride-based ILs with alkyl tail length variations are combined with commercially available, small-molecule antimicrobials to examine the potential for combinatorial and synergistic antimicrobial effects on P. aeruginosa, E. coli, S. aureus, and S. cerevisiae. The effects of these treatments in a human cell culture model indicate the cytotoxic limits of ILs paired with antimicrobials. The analysis of these ILs demonstrates that the length of the alkyl chain on the IL molecule is proportional to both antimicrobial activity and cytotoxicity. Moreover, the ILs which exhibit synergy with small-molecule antibiotics appear to be acting in a membrane permeabilizing manner. Collectively, results from these experiments demonstrate an increase in antimicrobial efficacy with specific IL + antimicrobial combinations on microbial cultures while maintaining low cytotoxicity in a mammalian cell culture model.

Impact of guidelines implementation for the rational use of prophylactic antibiotics in elective cesarean sections at Elqutainah Teaching Hospital

Background:The clinical pharmacists have a sensible role in the implementation of guidelines by ensuring proper patient selection and medication use. This study aimed to implement a hospital guideline for the rational use of prophylactic antibiotics in elective cesarean sections (ECS) by establishing compliance with international guidelines regarding prophylactic antibiotic use in ECS at Elqutainah Teaching Hospital in White Nile State, Sudan, and define the area of medication cost-saving.Methods:A quasi-experimental design without control group was used from April to June 2018. 195 participants were included, 94 participants before and 101 participants after the intervention and data were collected using a designed checklist by the researchers. The intervention is based on withdrawal metronidazole dosage forms from prophylactic antibiotics for ECS according to international guidelines in antibiotics prophylaxis toward ECS. Finally, the data were compared between pre- and post-intervention.Findings:Before intervention; all participants had received intravenous cefuroxime and metronidazole infusions prior ECS and oral cefuroxime or amoxicillin-clavulanic acid, and metronidazole for 7 days upon discharge. While after the intervention, all participants didn't receive any metronidazole dosage forms before and after ECS also didn't receive amoxicillin-clavulanic acid. However, the dosage regimen of cefuroxime didn't change. This intervention was meaningful in minimizing overuse of antibiotics prophylaxis in the ECS, and reducing staff workload along with medication cost.Conclusions:Clinical pharmacist intervention was concisely changing the physicians' practice toward using updated guidelines of the rational use of prophylactic antibiotics for ECS.

Effect of Ceftriaxone versus Amoxicillin + Clavulanic Acid for Treatment of Acute Bacterial Rhino Sinusitis: Short Course Therapy

BACKGROUND:Acute bacterial rhinosinusitis is one of upper respiratory tract infection that disturbs patient life and requires special consideration.AIM:To evaluate the efficiency of Ceftriaxone versus a high dose of Amoxicillin-clavulanic acid for the treatment of acute bacterial rhinosinusitis.PATIENTS AND METHOD:Observational retrospective study include120 patients of both sex classified into two groups equally conducted. G1 treated with Ceftriaxone 1 g intramuscular injection once daily while, G2 treated with oral Amoxicillin-clavulanic acid (875 mg/125 mg) twice daily for 3-4 days then, the outcome of treatment evaluated as a cure or failed at the fifth or fourth day of treatment.RESULTS:Significant cure response observed in Ceftriaxone treated patient’s P ≤ 0.05 and significant failure response observed in Amoxicillin-clavulanic acid-treated patients when groups compared with each other. About gender and age groups, no significant differences in number between group 1 and 2 P ≥ 0.05.CONCLUSION:Ceftriaxone found more effective in the treatment of acute bacterial sinusitis than Amoxicillin+ clavulanic acid. Amoxicillin+clavulanic acid associated with more male failure cases recorded than female.

Topical versus systemic antibiotics for chronic suppurative otitis media

Topical versus systemic antibiotics for chronic suppurative otitis media

Moraxella osloensis Bacteremia in an Immunocompetent Child

Abstract Moraxella osloensis has been reported in the literature as a rare cause of sepsis, central nervous system infection, chest infection, and endophthalmitis. In the present case, the organism was isolated from the blood of an 8-year-old immunocompetent boy. It could not be identified with VITEK-2 and API-20NE (bioMerieux SA, Marcy-l'Etoile, France). Latex-based bacterial antigen test (BD Directigen Meningitis Combo Test; Becton, Dickinson and Company, Sparks, Maryland, United States) was positive for Neisseria meningitidis A/Y. It was identified as M. osloensis using matrix-associated laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF) (Vitek MS, bioMerieux, Marcy-l'Etoile) (confidence level 99.9%) and 16S rRNA gene sequencing (99% sequence identity). The child responded well to ampicillin, and was discharged home after 4 days, on oral amoxicillin–clavulanic acid for the next 7 days. M. osloensis is a rare cause of bacteremia. It may masquerade as N. meningitidis in the routine tests performed in the routine microbiology laboratories. It is imperative to confirm the identification with MALDI-TOF or a molecular method to remove the false positive diagnosis of N. meningitidis, and to avoid the unnecessary use of prophylaxis with rifampicin or ciprofloxacin.

Persistent Bacterial Bronchitis: Time to Venture beyond the Umbrella.

Chronic cough in children is common and frequently mismanaged. In the past, cough was diagnosed as asthma and inappropriate asthma therapies prescribed and escalated. It has been realized that persistent bacterial bronchitis (PBB) is a common cause of wet cough and responds to oral antibiotics. The initial definition comprised a history of chronic wet cough, positive bronchoalveolar (BAL) cultures for a respiratory pathogen and response to a 2-week course of oral amoxicillin–clavulanic acid. This is now termed PBB-micro; PBB-clinical eliminates the need for BAL. PBB-extended is PBB-micro or PBB-clinical but resolution necessitating 4 weeks of antibiotics; and recurrent PBB is >3 attacks of PBB-micro or-clinical/year. However, the airway has only a limited range of responses to chronic inflammation and infection, and neutrophilic airway disease is seen in many other conditions, such as cystic fibrosis and primary ciliary dyskinesia, both chronic suppurative lung disease endotypes, whose recognition has led to huge scientific and clinical advances. There is an urgent need to extend endotyping into PBB, especially PBB-recurrent. We need to move from associative studies and, in particular, deploy sophisticated modern –omics technologies and systems biology, rather as has been done in the context of asthma in U-BIOPRED. In summary, the use of the term PBB has done signal service in pointing us away from prescribing asthma therapies to children with infected airways, but we now need to move beyond a simple description to teasing out underlying endotypes.

Acetylcysteine in the treatment of subacute sinusitis: A double-blind placebo-controlled clinical trial.

Sinusitis is a common disease with harmful effects on the health and finances of patients and the economy of the community. It is easily treated in most of its acute stages but is associated with some management difficulties as it goes toward chronicity. Therefore, we tried to improve the treatment of subacute sinusitis by using acetylcysteine, which is a safe mucolytic and antioxidant agent. Thirty-nine adult patients with subacute sinusitis proved by computed tomography (CT) were enrolled in a double-blind, placebo-controlled trial. They received oral amoxicillin-clavulanic acid and normal saline nasal drops for 10 days and oral pseudoephedrine for 7 days. In addition, the patients received acetylcysteine (600 mg orally, once daily) in the intervention group or placebo in the control group for 10 days. A paranasal CT scan was taken at baseline and 30 days after patients finished the treatment and was evaluated quantitatively by Lund-Mackay (LM) score. Symptoms and some aspects of quality of life also were assessed at baseline and 14 days after initiation and 30 days after termination of the treatment via the Sino-Nasal Outcome Test questionnaire. The groups showed no significant difference in LM score after treatment. A positive correlation was observed between the LM and SNOT-20 scores. We concluded that adding oral acetylcysteine to amoxicillin-clavulanic acid, pseudoephedrine, and intranasal normal saline has no benefit for the treatment of subacute sinusitis.

When horse serum meets dog bite

A 61-year-old woman visited our clinic to continue rabies post-exposure vaccination. She had sustained a dog bite on the right calf during a journey to South Asia seven days earlier. Immediately after the bite she received several injections on both upper arms, as well as around the bite site, at a local clinic. Active immunisation with Verorab®, intradermally applied at both deltoid areas on days 0 and 3, was documented on the vaccination card. Passive immunisation was not recorded. Simultaneous to post-exposure immunisation she was started on oral amoxicillin–clavulanic acid for 10 days. When we saw her on day 7 she presented with a well demarcated, slightly raised, warm, puritic, and painless erythema posterior to the bite site (Fig. 1A) and an identical lesion at the lateral thigh of the same leg (Fig. 1B). Considering ongoing antibiotic treatment and the distance of the two lesions to each other and the bite site, bacterial soft-tissue infection was unlikely. On inquiry the patient recalled an intra-dermal injection into the flexor surface of the right forearm approximately 15 min before receiving the injections around the bite site and the right thigh. This “sensitivity testing,” as well as the raised eosinophil count of 8% (WBC 8.1 × 103 μl−1), led us to conclude that this was a local hypersensitivity reaction to equine rabies immunoglobulin. The two skin lesions resolved spontaneously over the next 7 days. Fig. 1 (A) Right calf and (B) right thigh.

A Case of Liver Abscess with Desulfovibrio desulfuricans Bacteremia.

Desulfovibrio spp. are gram-negative, sulfate-reducing, and anaerobic bacteria found in the digestive tract of humans. Because Desulfovibrio spp. are infrequent causative agents of infectious diseases and are difficult to isolate and to identify from clinical specimens, the appropriate antibiotic therapy to infection with Desulfovibrio spp. has not been determined. We report the first case of liver abscess with bacteremia due to Desulfovibrio desulfuricans to show the clinical presentation and treatment. The patient was successfully treated with intravenous piperacillin-tazobactam and oral amoxicillin-clavulanic acid.

Oral amoxicillin-clavulanic Acid treatment in urinary tract infections caused by extended-spectrum Beta-lactamase-producing organisms.

Background:Extended-spectrum β-lactamases (ESBLs) are increasing problems. The involvement of ESBL-producing organisms is associated with higher rates of carbapenem usage in urinary tract infections (UTIs). Though some strains are susceptible to amoxicillin-clavulanic acid (AMC) in vitro, there is very less data about the consequences of AMC usage for such infections.Objectives:The purpose of this study was to evaluate the clinical and microbiological outcomes of AMC treatment in UTIs caused by AMC-susceptible ESBL-producing organisms.Patients and Methods:A retrospective cohort study was conducted in a tertiary care hospital. Forty-six out of 652 patients (F/M ratio: 32/14; mean age: 43.9 years) with ESBL-positive UTIs were eligible for this study. These patients had cystitis (n = 23), vesicoureteral reflux (n = 7), hyperactive bladder (n = 6), and prostatitis (n = 10). Data was collected via chart review and was statistically analyzed.Results:AMC-susceptible ESBL-producing Escherichia coli, Klebsiella pneumoniae and K. oxytoca were identified as the causative agents in 31, 14, and 1 patients, respectively. Thirty-nine (84.7%) out of 46 patients were successfully treated with oral AMC. Additionally, 2 (4.3%) patients’ urine cultures turned to be negative, though their clinical complaints and leukocyturia had continued. In the remaining 5 (10.8%) patients, no positive clinical and microbiological response was obtained. Increased minimum inhibitory concentration levels of AMC (from 4 to > 256 µg/mL) were detected in these patients and the treatment failures were attributed to this developing resistance. We found that therapeutic failure was significantly more frequent in Klebsiella spp. than in E. coli (33.3% vs 6.5%, P = 0.029). Furthermore, no treatment failure was observed in pathogens with minimum inhibitory concentrations (MICs) ≤ 2 mg/mL, and the high AMC MIC (8 mg/mL) was associated with resistance development and therapeutic failure (71.4% vs. 5.1%, P = 0.0001).Conclusions:Our results suggested that amoxicillin-clavulanic acid may be a good oral antimicrobial which can be used for treatment of ESBL-positive UTIs, if the causative agent is susceptible to this antibiotic. However, some strains may develop resistance during therapy, especially in those exhibiting high AMC MICs.

Procalcitonin

To the Editors: We report the case of a 21-year-old female who developed a serious bacterial infection while receiving the anti-interleukin-6 (IL-6) receptor monoclonal antibody tocilizumab and in whom the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) responses were blunted by her immunosuppressive therapy. Serum procalcitonin (PCT), however, remained a useful marker of the acute infection and her subsequent clinical improvement, suggesting an important role for PCT in the diagnosis of serious infection in patients receiving tocilizumab. A 21-year-old female with juvenile idiopathic arthritis and chronic abdominal pain presented to the emergency department with fever, abdominal pain, vomiting and diarrhea 1 day after her biweekly infusion of tocilizumab. Physical examination was unrevealing, and routine laboratory testing showed a white blood cell count of 8300/mm3 with 70% neutrophils, CRP <0.5 mg/dL (normal <1.0 mg/dL) and an ESR of 3 mm/hr, and she was discharged. She returned 1 day later with worsened abdominal pain and was hospitalized. Abdominal computed tomography and pelvic inflammatory disease testing were negative. On hospital day 2, acute otitis media was noted, and she developed a generalized erythrodermal rash with bullous sloughing consistent clinically and on subsequent biopsy with staphylococcal scalded-skin syndrome associated with the acute otitis media. She was treated with ampicillin-sulbactam and slowly improved. She was discharged completely recovered after 8 days of hospitalization on oral amoxicillin-clavulanic acid. Blood testing throughout showed persistently low ESR and CRP (Table 1). Given the suspected inhibition of these markers by tocilizumab, a serum procalcitonin test was ordered on hospital day 5 and retrospectively performed on 3 prior frozen serum samples, including 1 taken at the time of her initial Emergency Department presentation. The initial PCT of 15.96 ng/mL (normal 0.0–0.5 ng/mL) was highly suggestive of bacterial infection, and subsequent values showed a clear trend toward normalization, reaching 0.54 ng/mL by day 5 after exposure to antistaphylococcal therapy.TABLE 1: Laboratory and Temperature Values During Hospital CourseProcalcitonin, a 116 amino acid peptide precursor to calcitonin, is transcribed by the calcitonin-related polypeptide alpha gene on chromosome 11. In the setting of bacterial infection, PCT is released in large quantities in to the circulation from a wide range of differentiated parenchymal tissues, particularly fat cells.1 PCT release is driven in vivo primarily by the proinflammatory cytokines tumor necrosis factor-α and IL-1ß.2 IL-6 is a critical mediator of inflammation and plays a central role in the induction of acute phase reactants in the liver, including CRP and fibrinogen, the primary driver of elevated ESR. Other cytokines, notably IL-1 and tumor necrosis factor-α, which can also elevate CRP and ESR, appear to do so through stimulation of IL-6.3 Although IL-6 can stimulate PCT release in vitro, in vivo it is not essential and elevation of IL-6 can occur without a rise in PCT, as demonstrated in a study of 360 febrile children with proven viral infections.4,5 Little published information exists demonstrating the effects of biological immunosuppressant agents on the PCT compared with other acute phase reactants. Tocilizumab is a mouse derived, humanized monoclonal antibody directed against the IL-6 receptor. Given the central role of IL-6 in CRP and ESR elevation, and the distinct alternate pathways of procalcitonin release, an IL-6 inhibitor should blunt the response to CRP and ESR while allowing PCT to elevate in response to severe bacterial infection, as was demonstrated in this case. In patients undergoing therapy with IL-6 receptor inhibitors, PCT may be the preferred surrogate marker of bacterial infection. James T. Gaensbauer, MD, MScPH Craig A. Press, MD, PhD Department of Pediatrics Section on Infectious Diseases J. Roger Hollister, MD Department of Pediatrics Section of Allergy, Immunology and Rheumatology University of Colorado School of Medicine Aurora, CO Edwin J. Asturias, MD Department of Pediatrics Section on Infectious Diseases University of Colorado School of Medicine Aurora, CO Center for Global Health Colorado School of Public Health Aurora, CO

Long-Term Changes in Human Colonic Bifidobacterium Populations Induced by a 5-Day Oral Amoxicillin-Clavulanic Acid Treatment

The objective of this study was to assess the possible modifications due to amoxicillin-clavulanic acid (AMC) treatment on total bacteria and on Bifidobacterium species balance in human colonic microbiota. Eighteen healthy volunteers (19 to 36 years old) were given a 875/125 mg dose of AMC twice a day for 5 days. Fecal samples were obtained before and after antibiotic exposure. After total DNA extraction, total bacteria and bifidobacteria were specifically quantified using real-time PCR. Dominant species were monitored over time using bacterial and bifidobacterial Temporal Temperature Gradient gel Electrophoresis (TTGE). At the end of AMC exposure, total bacterial concentrations as well as bifidobacteria concentrations were significantly reduced compared to before AMC exposure:10.7±0.1 log10 16S rRNA gene copies/g vs 11.1±0.1 log10 (p = 0.003) and 8.1±0.5 log10 16S rRNA gene copies/g vs 9.4±0.3 log10 (p = 0.003), respectively. At the same time, the mean similarity percentages of TTGE bacteria and TTGE bifidobacteria profiles were significantly reduced compared to before AMC exposure: 51.6%±3.5% vs 81.4%±2.1% and 55.8%±7.6% vs 84.5%±4.1%, respectively. Occurrence of B. adolescentis, B. bifidum and B. pseudocatenulatum/B. catenulatum species significantly decreased. Occurrence of B. longum remained stable. Moreover, the number of distinct Bifidobacterium species per sample significantly decreased (1.5±0.3 vs 2.3±0.3; p = 0.01). Two months after AMC exposure, the mean similarity percentage of TTGE profiles was 55.6% for bacteria and 62.3% for bifidobacteria. These results clearly demonstrated that a common antibiotic treatment may qualitatively alter the colonic microbiota. Such modifications may have potential long-term physiological consequences.