Amoxicillin + Clavulanic Acid

Acute bacterial rhinosinusitis in adults and children when a bacterial cause is reasonably suspected (IDSA 2012, AAP 2013): symptoms lasting more than 10 days without improvement, worsening after initial improvement, or severe onset with fever ≥39 °C and purulent nasal discharge or facial pain for at least 3 consecutive days. IDSA 2012 recommends amoxicillin-clavulanate rather than amoxicillin as empirical first-line therapy in adults and children; AAP 2013 (children) and AAO-HNS 2015 (adults) name "amoxicillin with or without clavulanate" as first line and allow watchful waiting in uncomplicated cases. For children the Spanish framework differs: the pediatric SEIP/AEPap/SEPEAP/SEORL 2013 consensus and its 2023 update consider amoxicillin the drug of choice and keep the combination for selected cases (risk factors, amoxicillin failure). Per Cochrane 2018, the benefit of antibiotics in uncomplicated rhinosinusitis in adults is modest and adverse effects are more frequent. Adult dose: 875/125 mg every 12 h for 5–7 days (IDSA 2012; AAO-HNS 2015: 5–10 days); the Spanish SmPC gives 875/125 mg 2–3 times daily. IDSA 2012 reserves the high dose (2 g of amoxicillin twice daily; 90 mg/kg/day in children) for risk factors for resistance: age under 2 or over 65, daycare attendance, antibiotics or hospitalization in the past month, immunosuppression, severe illness. Children: 45 mg/kg/day of amoxicillin in two doses (IDSA 2012) for 10–14 days; in Spain the high dose is given with the 8:1 suspension (100/12.5 mg/ml). The 875/125 mg tablets are not recommended in severe kidney impairment (creatinine clearance below 30 ml/min). Contraindications (AEMPS SmPC, 4.3): penicillin allergy, anaphylaxis to other beta-lactams, and a history of jaundice or liver injury with amoxicillin-clavulanate. Possible cholestatic hepatitis, diarrhea up to C. difficile-associated colitis, and rash in infectious mononucleosis. Interactions: oral anticoagulants (higher INR), methotrexate, mycophenolate, allopurinol (more rash). Pregnancy (4.6): only if the doctor considers it essential; during breastfeeding the infant may develop diarrhea and candidiasis.

ICD-10: J01.9 · ICD-11: CA01

Animal or human bite with a risk of wound infection. Amoxicillin-clavulanate is the first-choice drug both for short prophylaxis and for treatment of an already infected wound: it covers Pasteurella, oral anaerobes and staphylococci (IDSA SSTI 2014, NICE NG184 2020); animal bites are listed in the Spanish SmPC (4.1). Per IDSA 2014, a 3–5-day preventive course is needed in immunosuppression, asplenia, advanced liver disease, edema of the bitten area, moderate or severe wounds, especially of the hand or face, and wounds that may have reached the periosteum or joint capsule; NICE NG184 adds human bites and deep cat bites. Per Cochrane 2001, prophylaxis reduced infection after hand bites and human bites, with no difference shown for dog bites overall, so a superficial low-risk wound does not need an antibiotic. An infected wound is treated for about 5 days with review (NICE NG184); fever, spreading redness or joint involvement require in-person assessment. Adult dose: 875/125 mg every 12 h (IDSA 2014); the Spanish SmPC gives 2–3 times daily. Tetanus and rabies prophylaxis are decided separately by the doctor. Contraindications (AEMPS SmPC, 4.3): penicillin allergy (per IDSA 2014 the alternative is doxycycline), anaphylaxis to other beta-lactams, and a history of jaundice or liver injury with the drug. Possible diarrhea up to C. difficile colitis and cholestatic hepatitis. Interactions: oral anticoagulants (higher INR), methotrexate, mycophenolate, allopurinol. Pregnancy (4.6): only if the doctor considers it essential; during breastfeeding the infant may develop diarrhea and candidiasis.

ICD-10: T14.1

Community-acquired pneumonia in adults: outpatients with comorbidities (heart, lung, liver or kidney disease, diabetes, alcohol dependence, cancer, asplenia) and inpatients outside the ICU. Per ATS/IDSA 2019, amoxicillin-clavulanate is a first-choice option for outpatients with comorbidities, always combined with a macrolide (azithromycin, clarithromycin) or doxycycline; for outpatients without comorbidities amoxicillin is preferred. NICE NG138 (2019) names amoxicillin-clavulanate with clarithromycin as first choice in high-severity pneumonia. The Spanish SEPAR 2020 guideline includes the drug in initial regimens for outpatients and non-ICU inpatients together with a macrolide. Adult dose: 875/125 mg every 12 h or 500/125 mg every 8 h (ATS/IDSA 2019); the Spanish SmPC gives 875/125 mg 2–3 times daily. Treat for at least 5 days and until clinical stability; reassess at 48–72 h, and if there is no response, reconsider the diagnosis and escalate. The 875/125 mg tablets are not recommended in severe kidney impairment (creatinine clearance below 30 ml/min). Contraindications (AEMPS SmPC, 4.3): penicillin allergy, anaphylaxis to other beta-lactams, and a history of jaundice or liver injury with amoxicillin-clavulanate. Possible cholestatic hepatitis (more often in men and older adults, with prolonged courses, sometimes after the course has ended), diarrhea up to C. difficile-associated colitis, and rash in infectious mononucleosis. Interactions: oral anticoagulants (higher INR), methotrexate (more toxicity), mycophenolate (lower levels), allopurinol (more rash); clarithromycin adds its own CYP3A4 interactions and QT prolongation risk. Pregnancy (4.6): only if the doctor considers it essential; during breastfeeding the infant may develop diarrhea and candidiasis.

ICD-10: J18.9 · ICD-11: CA40.Z

COPD exacerbation when an antibiotic is indicated: increased sputum purulence together with more dyspnea or more sputum, or an exacerbation requiring hospitalization or ventilation (GOLD, GesEPOC 2021). Per GOLD, initial empirical therapy is an aminopenicillin with clavulanic acid, a macrolide or a tetracycline, chosen by local resistance patterns; the Spanish GesEPOC 2021 places amoxicillin-clavulanate as first choice in mild and moderate exacerbations without Pseudomonas risk. NICE NG114 (2018) narrows the frame: first choices are amoxicillin, doxycycline or clarithromycin, with co-amoxiclav for a high risk of treatment failure. Per Cochrane 2018, antibiotics in outpatients reduce the risk of treatment failure (RR 0.72, 95% CI 0.56–0.94, low certainty) without affecting mortality, with a large effect in the ICU. Exacerbation of chronic bronchitis is listed in the Spanish SmPC (4.1). Adult dose: 875/125 mg every 8–12 h, usually 5–7 days (GOLD: 5–7 days). With Pseudomonas risk factors (frequent antibiotic courses, severe airflow limitation, previous isolation) a different drug is needed. The 875/125 mg tablets are not recommended when creatinine clearance is below 30 ml/min. Contraindications (AEMPS SmPC, 4.3): penicillin allergy, anaphylaxis to other beta-lactams, and a history of jaundice or liver injury with the drug. Possible cholestatic hepatitis (more often in older adults and with prolonged courses) and diarrhea up to C. difficile colitis. Interactions: oral anticoagulants (higher INR), methotrexate, mycophenolate, allopurinol.

ICD-10: J44.1 · ICD-11: CA22.0

Acute otitis media in children when antibiotics are indicated (age under 6 months, bilateral otitis in children under 2 years, severe pain, fever >39 °C, otorrhea with perforation). Amoxicillin-clavulanate is not the default starting antibiotic here: AAP 2013 and the Spanish consensus (SEIP/SEPEAP/SEUP/AEPap 2012, updated in 2023 with SEORL-CCC) name high-dose amoxicillin as the drug of choice. The combination is started up front if the child received amoxicillin in the last 30 days, has purulent conjunctivitis, or has recurrences unresponsive to amoxicillin (AAP 2013), and, per the Spanish 2012 consensus, in infants under 6 months, in severe illness (fever >39 °C or severe pain) and with a family history of otitis sequelae. If amoxicillin fails at 48–72 hours, it is the second line. Clavulanate blocks the beta-lactamases of H. influenzae and M. catarrhalis; it does nothing against pneumococcal resistance, which is covered by the high amoxicillin dose. In two placebo-controlled RCTs (Hoberman 2011, Tähtinen 2011) the drug reduced treatment failure, with more diarrhea and diaper dermatitis. Dose: 80–90 mg/kg/day of amoxicillin (AAP 2013: 90 mg/kg/day in two doses with the 14:1 formulation; Spanish consensus: 80 mg/kg/day); in Spain the high dose is given with the 8:1 suspension (100/12.5 mg/ml), 4:1 formulations are unsuitable because of excess clavulanate. Duration per AAP 2013: 10 days under 2 years and in severe illness, 7 days at 2–5 years, 5–7 days from 6 years; the Spanish 2023 consensus allows 5–7 days in mild uncomplicated otitis without risk factors. Contraindications (AEMPS SmPC, 4.3): penicillin allergy, anaphylaxis to other beta-lactams, and a history of jaundice or liver injury with amoxicillin-clavulanate.

ICD-10: H66.0 · ICD-11: AB00