Amoxicillin-Clavulanate Potass

Drug overview for AMOXICILLIN-CLAVULANATE POTASS (amoxicillin/potassium clavulanate):

Generic name: AMOXICILLIN/POTASSIUM CLAVULANATE (a-MOX-i-SIL-in/KLAV-ue-LAN-ik AS-id)
Drug class: Beta-Lactams
Therapeutic class: Anti-Infective Agents

Amoxicillin and clavulanate potassium (amoxicillin/clavulanate) is a fixed combination of amoxicillin trihydrate (an aminopenicillin antibiotic) and the potassium salt of clavulanic acid (a beta-lactamase inhibitor); clavulanic acid synergistically expands amoxicillin's spectrum of activity against many strains of beta-lactamase-producing bacteria.

The fixed combination of amoxicillin and clavulanate potassium (amoxicillin/clavulanate) is used orally for the treatment of lower respiratory tract infections, otitis media, sinusitis, skin and skin structure infections, and urinary tract infections caused by susceptible organisms. Amoxicillin/clavulanate is used principally for the treatment of infections caused by susceptible beta-lactamase-producing strains of Moraxella catarrhalis, Escherichia coli, Haemophilus influenzae, Klebsiella, and Staphylococcus aureus. Although amoxicillin/clavulanate also may be effective in the treatment of infections caused by non-beta-lactamase-producing organisms susceptible to amoxicillin alone, most clinicians state that an aminopenicillin used alone is preferred to the combination drug for the treatment of these infections and that amoxicillin/clavulanate should be reserved for use in the treatment of infections caused by, or suspected of being caused by, beta-lactamase-producing organisms when an aminopenicillin alone would be ineffective.

Prior to initiation of therapy with amoxicillin/clavulanate, appropriate specimens should be obtained for identification of the causative organism and in vitro susceptibility tests. Amoxicillin/clavulanate may be started pending results of susceptibility tests if the infection is believed to be caused by beta-lactamase-producing bacteria susceptible to the drug, but should be discontinued if the organism is found to be resistant to the drug. If the infection is found to be caused by non-beta-lactamase-producing organisms susceptible to aminopenicillins, some clinicians suggest that therapy generally should be changed to an aminopenicillin alone, unless this is impractical.

DRUG IMAGES

AMOX-CLAV 500-125 MG TABLET

The following indications for AMOXICILLIN-CLAVULANATE POTASS (amoxicillin/potassium clavulanate) have been approved by the FDA:

Indications:
Acute bacterial otitis media
Acute bacterial sinusitis
Acute Haemophilus influenzae bacterial sinusitis
Acute Moraxella catarrhalis bacterial sinusitis
Bacterial pneumonia
Bacterial urinary tract infection
E. coli urinary tract infection
Enterobacter cloacae urinary tract infection
Haemophilus influenzae bronchitis
Haemophilus influenzae chronic bronchitis
Haemophilus influenzae pneumonia
Klebsiella urinary tract infection
Moraxella catarrhalis bronchitis
Moraxella catarrhalis chronic bronchitis
Moraxella catarrhalis pneumonia
Skin and skin structure E. coli infection
Skin and skin structure infection
Skin and skin structure Klebsiella infection
Staphylococcus aureus skin and skin structure infection
Upper respiratory infection

Professional Synonyms:
Acute sinusitis due to B. catarrhalis
Acute sinusitis due to Branhamella catarrhalis
Acute sinusitis due to H. flu
Acute sinusitis due to H. influenzae
Acute sinusitis due to Haemophilus influenzae
Acute sinusitis due to Hemophilus influenzae
Acute sinusitis due to Influenza bacillus
Acute sinusitis due to M. catarrhalis
Acute sinusitis due to Moraxella catarrhalis
Acute sinusitis due to Neisseria catarrhalis
Acute sinusitis due to Pfeiffer's bacillus
Acute upper respiratory tract infection
Acute URI
Bacterial otitis media
Bronchitis due to B. catarrhalis
Bronchitis due to Branhamella catarrhalis
Bronchitis due to H. flu
Bronchitis due to H. influenzae
Bronchitis due to Haemophilus influenzae
Bronchitis due to Hemophilus influenzae
Bronchitis due to influenzae Bacillus
Bronchitis due to M. catarrhalis
Bronchitis due to Moraxella catarrhalis
Bronchitis due to Neisseria catarrhalis
Bronchitis due to Pfeiffer's Bacillus
Chronic bronchitis due to B. catarrhalis
Chronic bronchitis due to Branhamella catarrhalis
Chronic bronchitis due to H. flu
Chronic bronchitis due to H. influenzae
Chronic bronchitis due to Haemophilus influenzae
Chronic bronchitis due to Hemophilus influenzae
Chronic bronchitis due to influenza Bacillus
Chronic bronchitis due to M. catarrhalis
Chronic bronchitis due to Moraxella catarrhalis
Chronic bronchitis due to Neisseria catarrhalis
Chronic bronchitis due to Pfeiffer's Bacillus
E. coli UTI
H. flu pneumonia
H. influenzae pneumonia
Hemophilus influenzae pneumonia
Infection of skin and/or subcutaneous tissue
Influenza Bacillus pneumonia
Klebsiella UTI
Pfeiffer's Bacillus pneumonia
Pneumonia due to B. catarrhalis
Pneumonia due to Branhamella catarrhalis
Pneumonia due to Haemophilus influenzae
Pneumonia due to M. catarrhalis
Pneumonia due to Moraxella catarrhalis
Pneumonia due to Neisseria catarrhalis
Skin and skin soft tissue Escherichia coli infection
Skin and skin soft tissue infection due to Klebsiella
Skin and skin soft tissue Staphylococcus aureus infection
Skin and soft tissue skin infection
Urinary tract infection due to Enterobacter cloacae
Urinary tract infection due to Escherichia coli
Urinary tract infection due to Klebsiella species
UTI due to Enterobacter cloacae

The following dosing information is available for AMOXICILLIN-CLAVULANATE POTASS (amoxicillin/potassium clavulanate):

Dosing
Administration
AMOXICILLIN-CLAVULANATE POTASS
AMOXICILLIN-CLAVULANATE POTASS

Dosage of amoxicillin/clavulanate generally is expressed in terms of the amoxicillin content of the fixed combination. Although commercially available amoxicillin/clavulanate contains amoxicillin as the trihydrate and/or the sodium salt and clavulanic acid as the potassium salt, potency of amoxicillin is calculated on the anhydrous basis and potency of clavulanate potassium is expressed in terms of clavulanic acid.

Amoxicillin/clavulanate is commercially available for oral administration as a powder for oral suspension containing a 4:1, 7:1, or 14:1 ratio of amoxicillin to clavulanic acid; as chewable tablets containing a 4:1 or 7:1 ratio of the drugs; as film-coated tablets containing a 2:1 or 4:1 ratio of the drugs; as scored tablets containing a 7:1 ratio of the drugs; and as extended-release tablets containing a 16:1 ratio of the drugs.

Commercially available amoxicillin/clavulanate powders for oral suspension should not be considered interchangeable since they contain different amounts of clavulanic acid. The powder for oral suspension containing 600 mg of amoxicillin and 42.9 mg of clavulanic acid per 5 mL (Augmentin ES-600(R)) is indicated only for the treatment of persistent or recurrent acute otitis media (AOM) in certain pediatric patients 3 months to 12 years of age; safety and efficacy of this preparation in younger children or in adolescents or adults have not been established.

Because commercially available amoxicillin/clavulanate film-coated tablets containing 250 mg of amoxicillin contain 125 mg of clavulanic acid and commercially available chewable tablets containing 250 mg of amoxicillin contain 62.5 mg of clavulanic acid, these preparations should not be considered interchangeable. In addition, since the 250- and 500-mg film-coated tablets of the drug both contain the same amount of clavulanic acid, two 250-mg film-coated tablets are not equivalent to one 500-mg film-coated tablet.

Because extended-release tablets of amoxicillin/clavulanate contain different ratios of the drugs, the extended-release tablets are not equivalent to conventional or chewable tablets of the drug.

Children weighing less than 40 kg should not receive the 250-mg film-coated tablets since this formulation contains a higher dose of clavulanic acid. (See Dosage: Pediatric Dosage, under Dosage and Administration.) Safety and efficacy of the extended-release tablets have not been established in pediatric patients younger than 16 years of age.

The usual adult oral dosage of amoxicillin/clavulanate is one 250-mg film-coated tablet (containing 250 mg of amoxicillin and 125 mg of clavulanic acid) every 8 hours or one 500-mg film-coated tablet (containing 500 mg of amoxicillin and 125 mg of clavulanic acid) every 12 hours. For more severe infections and infections of the respiratory tract, the usual adult oral dosage is one 500-mg film-coated tablet (containing 500 mg of amoxicillin and 125 mg of clavulanic acid) every 8 hours or one 875-mg scored tablet (containing 875 mg of amoxicillin and 125 mg of clavulanic acid) every 12 hours. Alternatively, adults who have difficulty swallowing tablets may receive the oral suspension containing 125 or 250 mg of amoxicillin/5 mL instead of the 500-mg film-coated tablet or may receive the oral suspension containing 200 or 400 mg of amoxicillin/5 mL instead of the 875-mg scored tablet.

The usual oral dosage of amoxicillin/clavulanate extended-release tablets for the treatment of acute bacterial sinusitis in patients 16 years of age and older is 2 tablets (containing 1 g of amoxicillin and 62.5 mg of clavulanic acid in each tablet) every 12 hours for 10 days. The usual oral dosage of the extended-release tablets for the treatment of community-acquired pneumonia (CAP) in patients 16 years of age and older is 2 tablets (containing 1 g of amoxicillin and 62.5 mg of clavulanic acid in each tablet) every 12 hours for 7-10 days. Dosage adjustment for extended-release tablets of the combination based solely on age is not necessary in geriatric patients.

Children weighing 40 kg or more may receive the usual adult oral dosage of amoxicillin/clavulanate.

The usual dosage of amoxicillin/clavulanate in neonates and infants younger than 12 weeks of age is 30 mg/kg of amoxicillin daily given in divided doses every 12 hours. Because experience with the oral suspension containing 200 mg of amoxicillin/5 mL is limited in this age group, the manufacturer recommends that the oral suspension containing 125 mg of amoxicillin/5 mL be used in neonates and infants younger than 12 weeks of age.

For the treatment of sinusitis, lower respiratory tract infections, and more severe infections in pediatric patients 12 weeks of age and older, the usual dosage of amoxicillin/clavulanate is 45 mg/kg of amoxicillin daily in divided doses every 12 hours administered as the oral suspension containing 200 or 400 mg of amoxicillin/5 mL or as chewable tablets containing 200 or 400 mg of amoxicillin. Alternatively, these infections in this age group can be treated with a dosage of 40 mg/kg of amoxicillin daily in divided doses every 8 hours administered as the oral suspension containing 125 or 250 mg of amoxicillin/5 mL or as chewable tablets containing 125 or 250 mg of amoxicillin.

For the treatment of less severe infections in pediatric patients 12 weeks of age or older, the usual dosage of amoxicillin/clavulanate is 25 mg/kg of amoxicillin daily in divided doses every 12 hours administered as the oral suspension containing 200 or 400 mg of amoxicillin/5 mL or as chewable tablets containing 200 or 400 mg of amoxicillin. Alternatively, less severe infections in this age group can be treated with a dosage of 20 mg/kg of amoxicillin daily in divided doses every 8 hours administered as the oral suspension containing 125 or 250 mg of amoxicillin/5 mL or as chewable tablets containing 125 or 250 mg of amoxicillin.

In patients with renal impairment, doses and/or frequency of administration of amoxicillin/clavulanate should be modified in response to the degree of renal impairment. Some clinicians suggest that modification of usual dosage is unnecessary in adults with creatinine clearances greater than 30 mL/minute. These clinicians recommend that adults with creatinine clearances of 15-30 mL/minute receive the usual dose of conventional preparations of the drug every 12-18 hours, adults with creatinine clearances of 5-15 mL/minute receive the usual dose every 20-36 hours, and adults with creatinine clearances less than 5 mL/minute receive the usual dose every 48 hours.

However, other clinicians suggest that use of amoxicillin/clavulanate should be avoided in patients with creatinine clearances less than 30 mL/minute until more data are available on use of the drug in these patients.

Some clinicians suggest that adults undergoing hemodialysis receive a 500-mg tablet containing 500 mg of amoxicillin and 125 mg of clavulanic acid halfway through each dialysis period and an additional 500-mg tablet after each dialysis period.

The pharmacokinetics of extended-release tablets of amoxicillin/clavulanate have not been studied in patients with renal impairment, and the manufacturer states that this preparation is contraindicated in patients with severe impairment (creatinine clearance less than 30 mL/minute and those undergoing hemodialysis). The extended-release tablets should be dosed cautiously in patients with hepatic impairment and liver function should be monitored at frequent intervals.

No enhanced Administration information available for this drug.

Dosing information for AMOXICILLIN-CLAVULANATE POTASS
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
AMOX-CLAV 875-125 MG TABLET	Maintenance	Adults take 1 tablet by oral route every 12 hours
AMOX-CLAV 500-125 MG TABLET	Maintenance	Adults take 1 tablet by oral route every 12 hours

Generic dosing information for AMOXICILLIN-CLAVULANATE POTASS
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
AMOX-CLAV 500-125 MG TABLET	Maintenance	Adults take 1 tablet by oral route every 12 hours
AMOX-CLAV 875-125 MG TABLET	Maintenance	Adults take 1 tablet by oral route every 12 hours

The following drug interaction information is available for AMOXICILLIN-CLAVULANATE POTASS (amoxicillin/potassium clavulanate):

Contraindicated
Severe
Moderate

There are 1 contraindications. These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.

Drug Interaction	Drug Names
Live Typhoid Vaccine/Antimicrobials SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: The antimicrobial may be active against the organism in the live-vaccine. Antimicrobial therapy may prevent the vaccine organism from replicating enough to trigger an immune response.(1) CLINICAL EFFECTS: Vaccination may be ineffective. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Do not give oral typhoid vaccine until 72 hours after the last dose of antimicrobial. If possible, to optimize vaccine effectiveness, do not start antibacterial drugs for 72 hours after the last dose of oral typhoid vaccine. A longer interval should be considered for long-acting antimicrobials, such as azithromycin.(3) DISCUSSION: Because antimicrobial therapy may prevent sufficient vaccine-organism replication to generate an immune response, the manufacturer of live-attenuated typhoid vaccine and the Centers for Disease Control (CDC) state that the vaccine should not be administered to patients receiving antimicrobial therapy.(1-3)	VIVOTIF

Drug Interaction

Drug Names

Live Typhoid Vaccine/Antimicrobials

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: The antimicrobial may be active against the organism in the live-vaccine. Antimicrobial therapy may prevent the vaccine organism from replicating enough to trigger an immune response.(1)

CLINICAL EFFECTS: Vaccination may be ineffective.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Do not give oral typhoid vaccine until 72 hours after the last dose of antimicrobial. If possible, to optimize vaccine effectiveness, do not start antibacterial drugs for 72 hours after the last dose of oral typhoid vaccine. A longer interval should be considered for long-acting antimicrobials, such as azithromycin.(3)

DISCUSSION: Because antimicrobial therapy may prevent sufficient vaccine-organism replication to generate an immune response, the manufacturer of live-attenuated typhoid vaccine and the Centers for Disease Control (CDC) state that the vaccine should not be administered to patients receiving antimicrobial therapy.(1-3)

VIVOTIF

There are 2 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Methotrexate/Penicillins SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Penicillins may compete with the renal tubular secretion of methotrexate. CLINICAL EFFECTS: The concurrent use of methotrexate and penicillins may result in elevated levels of methotrexate and methotrexate toxicity, leading to increased risk of severe neurotoxicity, stomatitis, and myelosuppression. PREDISPOSING FACTORS: Risk factors for methotrexate toxicity include: - High-dose oncology regimens - Impaired renal function, ascites, or pleural effusions PATIENT MANAGEMENT: Patients receiving concurrent therapy with methotrexate and penicillins should be monitored closely for elevated methotrexate levels and methotrexate toxicity. The dose and duration of leucovorin rescue therapy may need to be increased. DISCUSSION: Elevated methotrexate levels, signs of methotrexate toxicity, and death have been reported following the concurrent use of methotrexate (both low dose and high dose) and penicillin derivatives. In a patient being treated with high-dose methotrexate (8 G/m2), the concurrent use of amoxicillin resulted in a 56% decrease in the clearance of methotrexate and signs of methotrexate toxicity.(1) There are two cases of methotrexate toxicity following the addition of amoxicillin to low-dose methotrexate therapy (7.5 mg-10 mg weekly) for psoriasis. In another case, a patient was found to have a toxic methotrexate level 12 days after her last dose of weekly methotrexate (7.5 mg). The patient had been treated with amoxicillin followed by flucloxacillin.(2) In a case report, dicloxacillin decreased methotrexate clearance 93%.(4) Flucloxacillin was shown to increase the area-under-curve (AUC) of methotrexate by 7.3% in a study in 10 subjects.(5) In a case report, a patient on low-dose methotrexate (5 mg) developed methotrexate pneumonia following the addition of flucloxacillin to his regimen.(5) In a patient being treated with high-dose methotrexate (12 G/m2), the concurrent use of mezlocillin increased the half-life of methotrexate from 10.1 to 27.2 hours.(6) In a case report, a patient developed methotrexate toxicity following the addition of penicillin V potassium to his methotrexate (50 mg weekly).(7) In a case report, penicillin decreased methotrexate clearance 36%.(4) In one report, leucovorin rescue therapy had to be continued for 192 hours following the concurrent use of methotrexate (3 G/m2) and piperacillin. During cycles without concurrent piperacillin, leucovorin rescue therapy was only required for 72 hours.(8) There are two reports of neutropenia and death following the concurrent use of piperacillin and low-dose methotrexate (2.5 mg three times weekly in one patient, 5 mg weekly in another) for psoriasis. One of these patients also received flucloxacillin. (3) In another case report, the concurrent use of piperacillin decreased methotrexate clearance by 67%.(4) In a case report, ticarcillin decreased methotrexate clearance by 60%.(4)	JYLAMVO, METHOTREXATE, METHOTREXATE SODIUM, OTREXUP, RASUVO, TREXALL, XATMEP
Fecal Microbiota Spores/Antibiotics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Fecal microbiota spores is a suspension of live bacterial spores, which may be compromised by concurrent use of antibiotics.(1) CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota spores.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota spores. Antibacterial treatment should be completed for 2 to 4 days before initiating treatment with fecal microbiota spores.(1) DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota spores.	VOWST

Drug Interaction

Drug Names

Methotrexate/Penicillins

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Penicillins may compete with the renal tubular secretion of methotrexate.

CLINICAL EFFECTS: The concurrent use of methotrexate and penicillins may result in elevated levels of methotrexate and methotrexate toxicity, leading to increased risk of severe neurotoxicity, stomatitis, and myelosuppression.

PREDISPOSING FACTORS: Risk factors for methotrexate toxicity include: - High-dose oncology regimens - Impaired renal function, ascites, or pleural effusions

PATIENT MANAGEMENT: Patients receiving concurrent therapy with methotrexate and penicillins should be monitored closely for elevated methotrexate levels and methotrexate toxicity. The dose and duration of leucovorin rescue therapy may need to be increased.

DISCUSSION: Elevated methotrexate levels, signs of methotrexate toxicity, and death have been reported following the concurrent use of methotrexate (both low dose and high dose) and penicillin derivatives. In a patient being treated with high-dose methotrexate (8 G/m2), the concurrent use of amoxicillin resulted in a 56% decrease in the clearance of methotrexate and signs of methotrexate toxicity.(1) There are two cases of methotrexate toxicity following the addition of amoxicillin to low-dose methotrexate therapy (7.5 mg-10 mg weekly) for psoriasis.

In another case, a patient was found to have a toxic methotrexate level 12 days after her last dose of weekly methotrexate (7.5 mg). The patient had been treated with amoxicillin followed by flucloxacillin.(2) In a case report, dicloxacillin decreased methotrexate clearance 93%.(4)

Flucloxacillin was shown to increase the area-under-curve (AUC) of methotrexate by 7.3% in a study in 10 subjects.(5) In a case report, a patient on low-dose methotrexate (5 mg) developed methotrexate pneumonia following the addition of flucloxacillin to his regimen.(5)

In a patient being treated with high-dose methotrexate (12 G/m2), the concurrent use of mezlocillin increased the half-life of methotrexate from 10.1 to 27.2 hours.(6)

In a case report, a patient developed methotrexate toxicity following the addition of penicillin V potassium to his methotrexate (50 mg weekly).(7) In a case report, penicillin decreased methotrexate clearance 36%.(4) In one report, leucovorin rescue therapy had to be continued for 192 hours following the concurrent use of methotrexate (3 G/m2) and piperacillin.

During cycles without concurrent piperacillin, leucovorin rescue therapy was only required for 72 hours.(8) There are two reports of neutropenia and death following the concurrent use of piperacillin and low-dose methotrexate (2.5 mg three times weekly in one patient, 5 mg weekly in another) for psoriasis. One of these patients also received flucloxacillin.

(3) In another case report, the concurrent use of piperacillin decreased methotrexate clearance by 67%.(4) In a case report, ticarcillin decreased methotrexate clearance by 60%.(4)

JYLAMVO, METHOTREXATE, METHOTREXATE SODIUM, OTREXUP, RASUVO, TREXALL, XATMEP

Fecal Microbiota Spores/Antibiotics

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Fecal microbiota spores is a suspension of live bacterial spores, which may be compromised by concurrent use of antibiotics.(1)

CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota spores.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota spores. Antibacterial treatment should be completed for 2 to 4 days before initiating treatment with fecal microbiota spores.(1)

DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota spores.

VOWST

There are 4 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
Oral Contraceptives/Penicillins SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Estrogens and progesterones are extensively excreted in bile, principally as glycuronide conjugates. Subsequently, they undergo enterohepatic circulation where bacterial hydrolysis occurs, allowing for reabsorption of the oral contraceptives through the bowel wall and eventual urinary excretion. Treatment with antibiotics destroys the gut flora and prevents steroid reabsorption, resulting in lower than normal concentrations of the contraceptive and excretion via the feces rather than the urine. CLINICAL EFFECTS: May observe reduced pharmacologic effects of oral contraceptives with resultant breakthrough bleeding and pregnancy. Reduced effects may be seen for several days after discontinuation of antibiotic therapy. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Current guidelines suggest that additional precautions are not necessary when non-enzyme inducing antibiotics are used concurrently with hormonal contraceptives; however, some patients may still prefer to use an additional method of contraception. DISCUSSION: Evidence for this interaction is limited and conflicting; however, the CDC and the Faculty of Sexual and Reproductive Healthcare Clinical Effectiveness Unit no longer recommend use of a backup contraceptive method during use of a non-enzyme inducing antibiotic. Reports of breakthrough bleeding and loss of contraceptive protection leading to unwanted pregnancies have occurred in women taking oral contraceptive agents who received concurrent ampicillin, amoxicillin, penicillin G, or oxacillin. Several studies have shown that the administration of ampicillin or penicillin to pregnant and nonpregnant women resulted in lowered urinary estrogen excretion, in some women as soon as three days after ampicillin therapy began. However in one small prospective study, plasma ethinyl estradiol concentrations showed a tendency to decrease during ampicillin administration on the third, fourth, and fifth morning of ampicillin administration, but were never lower than pretreatment values. In another small prospective study of women taking low dose combination contraceptives, concurrent ampicillin therapy neither altered the plasma levels nor the AUC of norethisterone and ethinyl estradiol. In addition, progesterone levels were in an anovulatory range. In another prospective study of 13 women taking long term oral contraceptive steroids, concurrent ampicillin was not associated with any significant changes in plasma concentrations of ethinyl estradiol, levonorgestrel, follicle stimulating hormone or progesterone, although lower concentrations of ethinyl estradiol were noted in two women.	2-METHOXYESTRADIOL, AFIRMELLE, ALTAVERA, ALYACEN, AMETHIA, AMETHYST, APRI, ARANELLE, ASHLYNA, AUBRA, AUBRA EQ, AUROVELA, AUROVELA 24 FE, AUROVELA FE, AVIANE, AYUNA, AZURETTE, BALCOLTRA, BALZIVA, BEYAZ, BLISOVI 24 FE, BLISOVI FE, BRIELLYN, CAMILA, CAMRESE, CAMRESE LO, CAZIANT, CHARLOTTE 24 FE, CHATEAL EQ, CRYSELLE, CYRED, CYRED EQ, DASETTA, DAYSEE, DEBLITANE, DESOGESTR-ETH ESTRAD ETH ESTRA, DIETHYLSTILBESTROL, DOLISHALE, DROSPIRENONE-ETH ESTRA-LEVOMEF, DROSPIRENONE-ETHINYL ESTRADIOL, ELINEST, ELLA, EMZAHH, ENPRESSE, ENSKYCE, ERRIN, ESTARYLLA, ESTRADIOL, ESTRADIOL BENZOATE, ESTRADIOL CYPIONATE, ESTRADIOL HEMIHYDRATE, ESTRADIOL HEMIHYDRATE MICRO, ESTRADIOL MICRONIZED, ESTRADIOL VALERATE, ESTRIOL, ESTRIOL MICRONIZED, ESTRONE, ETHINYL ESTRADIOL, ETHYNODIOL-ETHINYL ESTRADIOL, FALMINA, FEIRZA, FEMLYV, FINZALA, GEMMILY, HAILEY, HAILEY 24 FE, HAILEY FE, HEATHER, ICLEVIA, INCASSIA, ISIBLOOM, JAIMIESS, JASMIEL, JENCYCLA, JOLESSA, JOYEAUX, JULEBER, JUNEL, JUNEL FE, JUNEL FE 24, KAITLIB FE, KALLIGA, KARIVA, KELNOR 1-35, KELNOR 1-50, KURVELO, LARIN, LARIN 24 FE, LARIN FE, LAYOLIS FE, LEENA, LESSINA, LEVONEST, LEVONORG-ETH ESTRAD ETH ESTRAD, LEVONORG-ETH ESTRAD-FE BISGLYC, LEVONORGESTREL-ETH ESTRADIOL, LEVORA-28, LO LOESTRIN FE, LO-ZUMANDIMINE, LOESTRIN, LOESTRIN FE, LOJAIMIESS, LORYNA, LOW-OGESTREL, LUTERA, LYLEQ, LYZA, MARLISSA, MERZEE, MIBELAS 24 FE, MICROGESTIN, MICROGESTIN FE, MILI, MINZOYA, MONO-LINYAH, NATAZIA, NECON, NEXTSTELLIS, NIKKI, NORA-BE, NORETHIN-ETH ESTRA-FERROUS FUM, NORETHINDRON-ETHINYL ESTRADIOL, NORETHINDRONE, NORETHINDRONE-E.ESTRADIOL-IRON, NORGESTIMATE-ETHINYL ESTRADIOL, NORTREL, NYLIA, OCELLA, ORTHO TRI-CYCLEN, ORTHO-NOVUM, PHILITH, PIMTREA, PORTIA, RECLIPSEN, RIVELSA, SAFYRAL, SETLAKIN, SHAROBEL, SIMLIYA, SIMPESSE, SLYND, SPRINTEC, SRONYX, SYEDA, TARINA 24 FE, TARINA FE, TARINA FE 1-20 EQ, TAYTULLA, TILIA FE, TRI-ESTARYLLA, TRI-LEGEST FE, TRI-LINYAH, TRI-LO-ESTARYLLA, TRI-LO-MARZIA, TRI-LO-MILI, TRI-LO-SPRINTEC, TRI-MILI, TRI-SPRINTEC, TRI-VYLIBRA, TRI-VYLIBRA LO, TRIVORA-28, TULANA, TURQOZ, TYBLUME, VALTYA, VELIVET, VESTURA, VIENVA, VIORELE, VOLNEA, VYFEMLA, VYLIBRA, WERA, WYMZYA FE, XARAH FE, XELRIA FE, YASMIN 28, YAZ, ZARAH, ZOVIA 1-35, ZUMANDIMINE
Selected Anticoagulants (Vit K antag)/Selected Penicillins SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Unknown. CLINICAL EFFECTS: Large doses of parenterally administered penicillins and oral amoxicillin appear to increase the risk of bleeding during concurrent administration of anticoagulants. PREDISPOSING FACTORS: Renal failure may predispose patients to penicillin-induced coagulation abnormalities. A study suggests that various inflammatory syndromes or the nature of the infection can affect INR levels. The risk for bleeding episodes may be greater in patients with additional disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Monitor patient INR for an increase in the hypoprothrombinemic response to anticoagulants during concomitant administration of penicillins. Adjust the dose of warfarin accordingly. When concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin and/or hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: High dose parenteral administration of penicillins and oral amoxicillin have been reported to cause an increase in the hypoprothrombinemic effects of warfarin producing bleeding. Significant clinical effects have been reported with combined administration of warfarin and either carbenicillin or penicillin G. There have been several case reports and retrospective reviews documenting increased acenocoumarol and warfarin effects, including bleeding, following the addition of amoxicillin, with and without clavulanic acid, to therapy. In a randomized controlled trial, adult ambulatory patients that had no recent and ongoing infectious or inflammatory conditions received warfarin to a target INR between 2 and 3 with amoxicillin-clavulanic acid (1 gram twice daily for seven days) or placebo. The results showed the mean maximum INR increase from baseline to day 10 did not differ between amoxicillin/clavulanic acid (0.22 +/- 0.3) and the placebo period (0.24 +/- 0.6, p = 0.94). No patient experienced an INR of greater than 3.5. No bleeding events were reported during the entire study. A prospective cross-sectional observational study in 120 patients evaluated warfarin drug interactions, particularly with high-dose amoxicillin/clavulanate. The study found that patients on amoxicillin/clavulanate had a relative risk of having an INR >=4 of 4.8 compared to patients not on amoxicillin/clavulanate (95% CI 2.1-11.3, p < 0.001). This risk was primarily driven by patients on high-dose amoxicillin/clavulanate, who were 5.8 times more likely to have INR >=4 (95% CI 3.5-9.6, p<0.001). Significantly more patients on high-dose than normal dose amoxicillin/clavulanate had an INR value >= 4 (87.5% v. 28.9%, respectively). Nine out of ten patients who experienced bleeding during hospitalization were prescribed amoxicillin/clavulanate. A large systematic review was performed on 72 warfarin drug-drug interactions studies that reported on bleeding, thromboembolic events, or death. Most studies were retrospective cohorts. A meta-analysis of 11 of those studies found a higher rate of clinically significant bleeding in patients on warfarin and antimicrobials (OR=1.63; 95% CI 1.45-1.83). Increased bleeding risk was also seen in subgroup analyses with penicillins (OR=1.59; 95% CI 1.14-2.20) and amoxicillin (OR=1.78; 95% CI 1.14-2.79). A case-control nested cohort study of Medicare beneficiaries with warfarin prescriptions was evaluated for antibiotic use and warfarin toxicity in older adults. An increased risk of bleeding was associated with penicillins with an adjusted odds ratio of 1.92. Parenteral penicillins linked to this monograph include: almecillin, amdinocillin, amoxicillin, ampicillin, azlocillin, bacampicillin, carbenicillin, cyclacillin, hetacillin, mezlocillin, penicillin, penicillin G, penicillin V, phenethicillin, piperacillin, and ticarcillin. Oral penicillins linked to this monograph include: amoxicillin and penicillin.	ANISINDIONE, DICUMAROL, JANTOVEN, WARFARIN SODIUM
Selected Cephalosporins & Penicillins/Probenecid SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Probenecid impairs the clearance of some cephalosporins and penicillins via inhibition of renal anion transporters in the proximal tubule.(49) It has also been hypothesized that probenecid may affect tissue distribution of cephalosporins.(1-5) CLINICAL EFFECTS: The concurrent administration of probenecid may result in increased maximum concentration (Cmax), area-under-curve (AUC), and half-life of the cephalosporin or penicillin.(49) While this may improve antibiotic efficacy,(46-48) increased levels may also increase the risk for antibiotic-associated nephrotoxicity.(4) PREDISPOSING FACTORS: Underlying renal dysfunction may increase the risk for nephrotoxicity. PATIENT MANAGEMENT: In patients receiving the combination to improve antibiotic efficacy, monitor for antibiotic adverse effects and consider monitoring renal function. In patients receiving probenecid therapy to prevent or treat hyperuricemia, exposure to the antibiotic will be increased. A decrease in antibiotic dose or frequency may be required. The US manufacturer of piperacillin-tazobactam states probenecid should not be coadministered with piperacillin-tazobactam unless the benefit outweighs the risk.(50) DISCUSSION: Concurrent use of probenecid with a cephalosporin or penicillin may cause an increase in the Cmax, AUC, and an increased elimination half life of the antibiotic.(6-8,49) This may be beneficial or necessary in difficult to treat infections,(46-48) but an increased risk for adverse effects should be expected. Antibiotics not dose adjusted for concurrent use with probenecid may be associated with an increased risk for adverse effects, such as nephrotoxicity. Probenecid administered concurrently with piperacillin-tazobactam prolongs the half-life of piperacillin by 21% and tazobactam by 71%. In a study in 8 healthy males, concurrent administration of probenecid (1 g) with piperacillin (1 g IM) increased piperacillin's Cmax and AUC by 30% and 60%. Renal clearance was reduced by 40%.(51) The cephalosporins affected by probenecid include cefazolin,(9-11) cephacetrile,(12,13) cephaloglycin,(14,15) cephalexin,(16-21) cephradine, (22-23) cefoxitin,(24-28) cefadroxil(29), cefaclor,(23) cefamandole,(30) ceftizoxime,(31,32) cefuroxime,(33,34) cefprozil,(35) cefonicid,(36) cefmetazole,(37) cefmenoxime,(38) and cefditoren.(39) Probenecid has been shown not to affect moxalactam,(4,40,41) ceforanide, (4,42), cefoperazone, ceftazidime(4,34,43) or ceftriaxone.(4)	PROBENECID, PROBENECID-COLCHICINE
Allopurinol/Amoxicillin, Ampicillin, Bendamustine SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The exact mechanism is unknown. Allopurinol, amoxicillin, ampicillin, and bendamustine have been documented to cause cases of Stevens-Johnson syndrome (SJS), Toxic epidermal necrolysis (TEN), and Drug reaction with eosinophilia and systemic symptoms (DRESS).(1) CLINICAL EFFECTS: Concurrent administration of allopurinol with amoxicillin, ampicillin or bendamustine may result in an increased incidence of rash which may be severe. PREDISPOSING FACTORS: Patients who are HLA-B*58:01 positive may be at increased risk. PATIENT MANAGEMENT: Consider an alternative to amoxicillin, ampicillin, or bendamustine in patients with a history of serious skin rashes, such as SJS, TEN, or DRESS. Discontinue allopurinol at the first appearance of skin rash or other signs which may indicate a hypersensitivity reaction when used with amoxicillin or ampicillin or bendamustine. Instruct patients to seek medical attention for any peeling skin rash or blisters.(1) DISCUSSION: In the Boston Collaborative Drug Surveillance Program, drug rash was seen in 22.4% of 67 hospitalized patients (relative risk 3.0) receiving concurrent allopurinol and ampicillin compared to 7.5% of 1257 patients receiving only ampicillin and 2.1% of 283 patients rceiving only allopurinol.(4) A hospital drug monitoring program found the observed risk of developing an exanthema with concurrent use is as follows: aminopenicillin without allopurinol 10.1%, aminopenicillin combined with allopurinol 7.2%, allopurinol without aminopenicillin 3.0%, or neither of the two drugs 1.5%.(6) A case-control study did not find a statistically significant increased risk of SJS with concurrent use of allopurinol and amoxicillin or ampicillin (allopurinol alone 4.4% vs. with amoxicillin 6.8%; allopurinol alone 0.1% vs. with ampicillin 2.7% at 1 month)(allopurinol alone 4.4% vs. with amoxicillin 5.7% or allopurinol alone 0.2% vs. with ampicillin 2.9% at 3 months).(8) In a retrospective study looking at mortality data, records were screened for administration of high risk drugs associated with SJS. Allopurinol and ampicillin was one of the drug combinations listed as contributing to mortality in patients (p = 0.049).(9)	ALLOPURINOL, ALLOPURINOL SODIUM, ALOPRIM, DUZALLO, ZYLOPRIM

The following contraindication information is available for AMOXICILLIN-CLAVULANATE POTASS (amoxicillin/potassium clavulanate):

Overview
Contraindicated
Severe
Moderate

Drug contraindication overview.

No enhanced Contraindications information available for this drug.

There are 0 contraindications.

There are 4 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
Chronic kidney disease stage 5 (failure) GFr<15 ml/min
Clostridioides difficile infection
Infectious mononucleosis

There are 1 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Kidney disease with likely reduction in glomerular filtration rate (GFr)

The following adverse reaction information is available for AMOXICILLIN-CLAVULANATE POTASS (amoxicillin/potassium clavulanate):

Overview
Severe
Less Severe

Adverse reaction overview.

No enhanced Common Adverse Effects information available for this drug.

There are 50 severe adverse reactions.

More Frequent	Less Frequent
None.	Anaphylaxis Dyspnea Serum sickness

Rare/Very Rare
Acute coronary syndrome Acute generalized exanthematous pustulosis Acute pancreatitis Agranulocytosis Allergic dermatitis Anemia Angioedema Cholestasis Cholestatic hepatitis Clostridioides difficile infection DRESS syndrome Edema Enterocolitis Eosinophilia Eosinophilic pneumonia Erythema multiforme Exfoliative dermatitis Hemolytic anemia Hepatitis Hepatocellular damage Hyperbilirubinemia Hypersensitivity angiitis Hypersensitivity drug reaction Hypotension Increased alanine transaminase Increased alkaline phosphatase Increased aspartate transaminase Increased risk of bleeding due to coagulation disorder Interstitial nephritis Jaundice Kidney disease with reduction in glomerular filtration rate (GFr) Kounis syndrome Leukopenia Linear immunoglobulin A bullous dermatosis Multiple organ failure Non-infective meningitis Obstructive hyperbilirubinemia Pancytopenia Qualitative platelet disorder Seizure disorder Stevens-johnson syndrome Symmetrical drug-related intertriginous and flexural exanthema Thrombocytopenic disorder Thrombocytosis Thrombophlebitis Thrombotic thrombocytopenic purpura Toxic epidermal necrolysis

Rare/Very Rare

Acute coronary syndrome
Acute generalized exanthematous pustulosis
Acute pancreatitis
Agranulocytosis
Allergic dermatitis
Anemia
Angioedema
Cholestasis
Cholestatic hepatitis
Clostridioides difficile infection
DRESS syndrome
Edema
Enterocolitis
Eosinophilia
Eosinophilic pneumonia
Erythema multiforme
Exfoliative dermatitis
Hemolytic anemia
Hepatitis
Hepatocellular damage
Hyperbilirubinemia
Hypersensitivity angiitis
Hypersensitivity drug reaction
Hypotension
Increased alanine transaminase
Increased alkaline phosphatase
Increased aspartate transaminase
Increased risk of bleeding due to coagulation disorder
Interstitial nephritis
Jaundice
Kidney disease with reduction in glomerular filtration rate (GFr)
Kounis syndrome
Leukopenia
Linear immunoglobulin A bullous dermatosis
Multiple organ failure
Non-infective meningitis
Obstructive hyperbilirubinemia
Pancytopenia
Qualitative platelet disorder
Seizure disorder
Stevens-johnson syndrome
Symmetrical drug-related intertriginous and flexural exanthema
Thrombocytopenic disorder
Thrombocytosis
Thrombophlebitis
Thrombotic thrombocytopenic purpura
Toxic epidermal necrolysis

There are 39 less severe adverse reactions.

More Frequent	Less Frequent
Diarrhea Gastrointestinal irritation Headache disorder Loose stools Oral candidiasis Vulvovaginal candidiasis	Constipation Insomnia Nausea Phlebitis after infusion Pruritus of skin Skin rash Urticaria Vomiting

Rare/Very Rare
Acute abdominal pain Acute cognitive impairment Agitation Back pain Black tarry stools Chills Crystalluria Dental discoloration Dizziness Dysgeusia Dyspepsia Fever Flatulence Furred tongue Gastritis Glossitis Hematuria Injection site sequelae Malaise Mucocutaneous candidiasis Myalgia Stomatitis Symptoms of anxiety Tremor Vaginitis

The following precautions are available for AMOXICILLIN-CLAVULANATE POTASS (amoxicillin/potassium clavulanate):

Pediatric
Pregnant
Lactation
Geriatric

No enhanced Pediatric Use information available for this drug.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

Safe use of amoxicillin/clavulanate during pregnancy has not been definitely established. There are no adequate or controlled studies using amoxicillin/clavulanate in pregnant women, and the drug should be used during pregnancy only when clearly needed. Aminopenicillins are generally poorly absorbed when given orally during labor.

Although the mechanism is unclear and the clinical importance has not been determined to date, studies using oral ampicillin indicate that, when administered during pregnancy, the drug interferes with metabolism and enterohepatic circulation of steroids resulting in decreased urinary concentrations of estrogen metabolites. The manufacturers state that this effect could also occur with amoxicillin/clavulanate. IV administration of ampicillin to guinea pigs has decreased uterine tone and decreased the frequency, height, and duration of uterine contractions; however, it is not known whether use of amoxicillin/clavulanate in humans during labor or delivery could have any immediate or delayed adverse effects on the fetus, prolong the duration of labor, or increase the likelihood of forceps delivery, other obstetrical intervention, or resuscitation of the neonate.

Because amoxicillin and clavulanic acid are distributed into milk, amoxicillin/clavulanate should be used with caution in nursing women.

No enhanced Geriatric Use information available for this drug.

The following icd codes are available for AMOXICILLIN-CLAVULANATE POTASS (amoxicillin/potassium clavulanate)'s list of indications:

Acute bacterial otitis media
H66	Suppurative and unspecified otitis media
H66.0	Acute suppurative otitis media
H66.00	Acute suppurative otitis media without spontaneous rupture of ear drum
H66.001	Acute suppurative otitis media without spontaneous rupture of ear drum, right ear
H66.002	Acute suppurative otitis media without spontaneous rupture of ear drum, left ear
H66.003	Acute suppurative otitis media without spontaneous rupture of ear drum, bilateral
H66.004	Acute suppurative otitis media without spontaneous rupture of ear drum, recurrent, right ear
H66.005	Acute suppurative otitis media without spontaneous rupture of ear drum, recurrent, left ear
H66.006	Acute suppurative otitis media without spontaneous rupture of ear drum, recurrent, bilateral
H66.007	Acute suppurative otitis media without spontaneous rupture of ear drum, recurrent, unspecified ear
H66.009	Acute suppurative otitis media without spontaneous rupture of ear drum, unspecified ear
H66.01	Acute suppurative otitis media with spontaneous rupture of ear drum
H66.011	Acute suppurative otitis media with spontaneous rupture of ear drum, right ear
H66.012	Acute suppurative otitis media with spontaneous rupture of ear drum, left ear
H66.013	Acute suppurative otitis media with spontaneous rupture of ear drum, bilateral
H66.014	Acute suppurative otitis media with spontaneous rupture of ear drum, recurrent, right ear
H66.015	Acute suppurative otitis media with spontaneous rupture of ear drum, recurrent, left ear
H66.016	Acute suppurative otitis media with spontaneous rupture of ear drum, recurrent, bilateral
H66.017	Acute suppurative otitis media with spontaneous rupture of ear drum, recurrent, unspecified ear
H66.019	Acute suppurative otitis media with spontaneous rupture of ear drum, unspecified ear
H66.4	Suppurative otitis media, unspecified
H66.40	Suppurative otitis media, unspecified, unspecified ear
H66.41	Suppurative otitis media, unspecified, right ear
H66.42	Suppurative otitis media, unspecified, left ear
H66.43	Suppurative otitis media, unspecified, bilateral
H66.9	Otitis media, unspecified
H66.90	Otitis media, unspecified, unspecified ear
H66.91	Otitis media, unspecified, right ear
H66.92	Otitis media, unspecified, left ear
H66.93	Otitis media, unspecified, bilateral
Acute bacterial sinusitis
J01	Acute sinusitis
J01.0	Acute maxillary sinusitis
J01.00	Acute maxillary sinusitis, unspecified
J01.01	Acute recurrent maxillary sinusitis
J01.1	Acute frontal sinusitis
J01.10	Acute frontal sinusitis, unspecified
J01.11	Acute recurrent frontal sinusitis
J01.2	Acute ethmoidal sinusitis
J01.20	Acute ethmoidal sinusitis, unspecified
J01.21	Acute recurrent ethmoidal sinusitis
J01.3	Acute sphenoidal sinusitis
J01.30	Acute sphenoidal sinusitis, unspecified
J01.31	Acute recurrent sphenoidal sinusitis
J01.4	Acute pansinusitis
J01.40	Acute pansinusitis, unspecified
J01.41	Acute recurrent pansinusitis
J01.8	Other acute sinusitis
J01.80	Other acute sinusitis
J01.81	Other acute recurrent sinusitis
J01.9	Acute sinusitis, unspecified
J01.90	Acute sinusitis, unspecified
J01.91	Acute recurrent sinusitis, unspecified
Acute haemophilus influenzae bacterial sinusitis
B96.3	Hemophilus influenzae [h. influenzae] as the cause of diseases classified elsewhere
J01	Acute sinusitis
J01.0	Acute maxillary sinusitis
J01.00	Acute maxillary sinusitis, unspecified
J01.01	Acute recurrent maxillary sinusitis
J01.1	Acute frontal sinusitis
J01.10	Acute frontal sinusitis, unspecified
J01.11	Acute recurrent frontal sinusitis
J01.2	Acute ethmoidal sinusitis
J01.20	Acute ethmoidal sinusitis, unspecified
J01.21	Acute recurrent ethmoidal sinusitis
J01.3	Acute sphenoidal sinusitis
J01.30	Acute sphenoidal sinusitis, unspecified
J01.31	Acute recurrent sphenoidal sinusitis
J01.4	Acute pansinusitis
J01.40	Acute pansinusitis, unspecified
J01.41	Acute recurrent pansinusitis
J01.8	Other acute sinusitis
J01.80	Other acute sinusitis
J01.81	Other acute recurrent sinusitis
J01.9	Acute sinusitis, unspecified
J01.90	Acute sinusitis, unspecified
J01.91	Acute recurrent sinusitis, unspecified
Acute moraxella catarrhalis bacterial sinusitis
J01	Acute sinusitis
J01.0	Acute maxillary sinusitis
J01.00	Acute maxillary sinusitis, unspecified
J01.01	Acute recurrent maxillary sinusitis
J01.1	Acute frontal sinusitis
J01.10	Acute frontal sinusitis, unspecified
J01.11	Acute recurrent frontal sinusitis
J01.2	Acute ethmoidal sinusitis
J01.20	Acute ethmoidal sinusitis, unspecified
J01.21	Acute recurrent ethmoidal sinusitis
J01.3	Acute sphenoidal sinusitis
J01.30	Acute sphenoidal sinusitis, unspecified
J01.31	Acute recurrent sphenoidal sinusitis
J01.4	Acute pansinusitis
J01.40	Acute pansinusitis, unspecified
J01.41	Acute recurrent pansinusitis
J01.8	Other acute sinusitis
J01.80	Other acute sinusitis
J01.81	Other acute recurrent sinusitis
J01.9	Acute sinusitis, unspecified
J01.90	Acute sinusitis, unspecified
J01.91	Acute recurrent sinusitis, unspecified
Bacterial pneumonia
J15.9	Unspecified bacterial pneumonia
Bacterial urinary tract infection
N30.0	Acute cystitis
N30.00	Acute cystitis without hematuria
N30.01	Acute cystitis with hematuria
N30.9	Cystitis, unspecified
N30.90	Cystitis, unspecified without hematuria
N30.91	Cystitis, unspecified with hematuria
N39.0	Urinary tract infection, site not specified
O23.0	Infections of kidney in pregnancy
O23.00	Infections of kidney in pregnancy, unspecified trimester
O23.01	Infections of kidney in pregnancy, first trimester
O23.02	Infections of kidney in pregnancy, second trimester
O23.03	Infections of kidney in pregnancy, third trimester
O23.1	Infections of bladder in pregnancy
O23.10	Infections of bladder in pregnancy, unspecified trimester
O23.11	Infections of bladder in pregnancy, first trimester
O23.12	Infections of bladder in pregnancy, second trimester
O23.13	Infections of bladder in pregnancy, third trimester
O23.2	Infections of urethra in pregnancy
O23.20	Infections of urethra in pregnancy, unspecified trimester
O23.21	Infections of urethra in pregnancy, first trimester
O23.22	Infections of urethra in pregnancy, second trimester
O23.23	Infections of urethra in pregnancy, third trimester
O23.3	Infections of other parts of urinary tract in pregnancy
O23.30	Infections of other parts of urinary tract in pregnancy, unspecified trimester
O23.31	Infections of other parts of urinary tract in pregnancy, first trimester
O23.32	Infections of other parts of urinary tract in pregnancy, second trimester
O23.33	Infections of other parts of urinary tract in pregnancy, third trimester
O23.4	Unspecified infection of urinary tract in pregnancy
O23.40	Unspecified infection of urinary tract in pregnancy, unspecified trimester
O23.41	Unspecified infection of urinary tract in pregnancy, first trimester
O23.42	Unspecified infection of urinary tract in pregnancy, second trimester
O23.43	Unspecified infection of urinary tract in pregnancy, third trimester
O23.90	Unspecified genitourinary tract infection in pregnancy, unspecified trimester
O23.91	Unspecified genitourinary tract infection in pregnancy, first trimester
O23.92	Unspecified genitourinary tract infection in pregnancy, second trimester
O23.93	Unspecified genitourinary tract infection in pregnancy, third trimester
P39.3	Neonatal urinary tract infection
T83	Complications of genitourinary prosthetic devices, implants and grafts
T83.5	Infection and inflammatory reaction due to prosthetic device, implant and graft in urinary system
T83.51	Infection and inflammatory reaction due to urinary catheter
T83.59	Infection and inflammatory reaction due to prosthetic device, implant and graft in urinary system
T83.6	Infection and inflammatory reaction due to prosthetic device, implant and graft in genital tract
E. coli urinary tract infection
B96.2	Escherichia coli [e. coli ] as the cause of diseases classified elsewhere
B96.20	Unspecified escherichia coli [e. coli] as the cause of diseases classified elsewhere
B96.29	Other escherichia coli [e. coli] as the cause of diseases classified elsewhere
N30.0	Acute cystitis
N30.00	Acute cystitis without hematuria
N30.01	Acute cystitis with hematuria
N30.9	Cystitis, unspecified
N30.90	Cystitis, unspecified without hematuria
N30.91	Cystitis, unspecified with hematuria
N39.0	Urinary tract infection, site not specified
O23.0	Infections of kidney in pregnancy
O23.00	Infections of kidney in pregnancy, unspecified trimester
O23.01	Infections of kidney in pregnancy, first trimester
O23.02	Infections of kidney in pregnancy, second trimester
O23.03	Infections of kidney in pregnancy, third trimester
O23.1	Infections of bladder in pregnancy
O23.10	Infections of bladder in pregnancy, unspecified trimester
O23.11	Infections of bladder in pregnancy, first trimester
O23.12	Infections of bladder in pregnancy, second trimester
O23.13	Infections of bladder in pregnancy, third trimester
O23.2	Infections of urethra in pregnancy
O23.20	Infections of urethra in pregnancy, unspecified trimester
O23.21	Infections of urethra in pregnancy, first trimester
O23.22	Infections of urethra in pregnancy, second trimester
O23.23	Infections of urethra in pregnancy, third trimester
O23.3	Infections of other parts of urinary tract in pregnancy
O23.30	Infections of other parts of urinary tract in pregnancy, unspecified trimester
O23.31	Infections of other parts of urinary tract in pregnancy, first trimester
O23.32	Infections of other parts of urinary tract in pregnancy, second trimester
O23.33	Infections of other parts of urinary tract in pregnancy, third trimester
O23.4	Unspecified infection of urinary tract in pregnancy
O23.40	Unspecified infection of urinary tract in pregnancy, unspecified trimester
O23.41	Unspecified infection of urinary tract in pregnancy, first trimester
O23.42	Unspecified infection of urinary tract in pregnancy, second trimester
O23.43	Unspecified infection of urinary tract in pregnancy, third trimester
O23.9	Unspecified genitourinary tract infection in pregnancy
O23.90	Unspecified genitourinary tract infection in pregnancy, unspecified trimester
O23.91	Unspecified genitourinary tract infection in pregnancy, first trimester
O23.92	Unspecified genitourinary tract infection in pregnancy, second trimester
O23.93	Unspecified genitourinary tract infection in pregnancy, third trimester
Enterobacter cloacae urinary tract infection
B96.89	Other specified bacterial agents as the cause of diseases classified elsewhere
N30.0	Acute cystitis
N30.00	Acute cystitis without hematuria
N30.01	Acute cystitis with hematuria
N30.9	Cystitis, unspecified
N30.90	Cystitis, unspecified without hematuria
N30.91	Cystitis, unspecified with hematuria
N39.0	Urinary tract infection, site not specified
O23.0	Infections of kidney in pregnancy
O23.00	Infections of kidney in pregnancy, unspecified trimester
O23.01	Infections of kidney in pregnancy, first trimester
O23.02	Infections of kidney in pregnancy, second trimester
O23.03	Infections of kidney in pregnancy, third trimester
O23.1	Infections of bladder in pregnancy
O23.10	Infections of bladder in pregnancy, unspecified trimester
O23.11	Infections of bladder in pregnancy, first trimester
O23.12	Infections of bladder in pregnancy, second trimester
O23.13	Infections of bladder in pregnancy, third trimester
O23.2	Infections of urethra in pregnancy
O23.20	Infections of urethra in pregnancy, unspecified trimester
O23.21	Infections of urethra in pregnancy, first trimester
O23.22	Infections of urethra in pregnancy, second trimester
O23.23	Infections of urethra in pregnancy, third trimester
O23.3	Infections of other parts of urinary tract in pregnancy
O23.30	Infections of other parts of urinary tract in pregnancy, unspecified trimester
O23.31	Infections of other parts of urinary tract in pregnancy, first trimester
O23.32	Infections of other parts of urinary tract in pregnancy, second trimester
O23.33	Infections of other parts of urinary tract in pregnancy, third trimester
O23.4	Unspecified infection of urinary tract in pregnancy
O23.40	Unspecified infection of urinary tract in pregnancy, unspecified trimester
O23.41	Unspecified infection of urinary tract in pregnancy, first trimester
O23.42	Unspecified infection of urinary tract in pregnancy, second trimester
O23.43	Unspecified infection of urinary tract in pregnancy, third trimester
O23.9	Unspecified genitourinary tract infection in pregnancy
O23.90	Unspecified genitourinary tract infection in pregnancy, unspecified trimester
O23.91	Unspecified genitourinary tract infection in pregnancy, first trimester
O23.92	Unspecified genitourinary tract infection in pregnancy, second trimester
O23.93	Unspecified genitourinary tract infection in pregnancy, third trimester
Haemophilus influenzae bronchitis
J20.1	Acute bronchitis due to hemophilus influenzae
Haemophilus influenzae chronic bronchitis
J44.0	Chronic obstructive pulmonary disease with (acute) lower respiratory infection
Haemophilus influenzae pneumonia
J14	Pneumonia due to hemophilus influenzae
Klebsiella urinary tract infection
B96.1	Klebsiella pneumoniae [k. pneumoniae] as the cause of diseases classified elsewhere
N30.0	Acute cystitis
N30.00	Acute cystitis without hematuria
N30.01	Acute cystitis with hematuria
N30.9	Cystitis, unspecified
N30.90	Cystitis, unspecified without hematuria
N30.91	Cystitis, unspecified with hematuria
N39.0	Urinary tract infection, site not specified
O23.0	Infections of kidney in pregnancy
O23.00	Infections of kidney in pregnancy, unspecified trimester
O23.01	Infections of kidney in pregnancy, first trimester
O23.02	Infections of kidney in pregnancy, second trimester
O23.03	Infections of kidney in pregnancy, third trimester
O23.1	Infections of bladder in pregnancy
O23.10	Infections of bladder in pregnancy, unspecified trimester
O23.11	Infections of bladder in pregnancy, first trimester
O23.12	Infections of bladder in pregnancy, second trimester
O23.13	Infections of bladder in pregnancy, third trimester
O23.2	Infections of urethra in pregnancy
O23.20	Infections of urethra in pregnancy, unspecified trimester
O23.21	Infections of urethra in pregnancy, first trimester
O23.22	Infections of urethra in pregnancy, second trimester
O23.23	Infections of urethra in pregnancy, third trimester
O23.3	Infections of other parts of urinary tract in pregnancy
O23.30	Infections of other parts of urinary tract in pregnancy, unspecified trimester
O23.31	Infections of other parts of urinary tract in pregnancy, first trimester
O23.32	Infections of other parts of urinary tract in pregnancy, second trimester
O23.33	Infections of other parts of urinary tract in pregnancy, third trimester
O23.4	Unspecified infection of urinary tract in pregnancy
O23.40	Unspecified infection of urinary tract in pregnancy, unspecified trimester
O23.41	Unspecified infection of urinary tract in pregnancy, first trimester
O23.42	Unspecified infection of urinary tract in pregnancy, second trimester
O23.43	Unspecified infection of urinary tract in pregnancy, third trimester
O23.9	Unspecified genitourinary tract infection in pregnancy
O23.90	Unspecified genitourinary tract infection in pregnancy, unspecified trimester
O23.91	Unspecified genitourinary tract infection in pregnancy, first trimester
O23.92	Unspecified genitourinary tract infection in pregnancy, second trimester
O23.93	Unspecified genitourinary tract infection in pregnancy, third trimester
Moraxella catarrhalis bronchitis
B96.89	Other specified bacterial agents as the cause of diseases classified elsewhere
J20.8	Acute bronchitis due to other specified organisms
Moraxella catarrhalis chronic bronchitis
J44.0	Chronic obstructive pulmonary disease with (acute) lower respiratory infection
Moraxella catarrhalis pneumonia
J15.6	Pneumonia due to other gram-negative bacteria
Skin and skin structure e. coli infection
B96.2	Escherichia coli [e. coli ] as the cause of diseases classified elsewhere
B96.20	Unspecified escherichia coli [e. coli] as the cause of diseases classified elsewhere
B96.29	Other escherichia coli [e. coli] as the cause of diseases classified elsewhere
L08.9	Local infection of the skin and subcutaneous tissue, unspecified
Skin and skin structure infection
H05.01	Cellulitis of orbit
H05.011	Cellulitis of right orbit
H05.012	Cellulitis of left orbit
H05.013	Cellulitis of bilateral orbits
H05.019	Cellulitis of unspecified orbit
H60.1	Cellulitis of external ear
H60.10	Cellulitis of external ear, unspecified ear
H60.11	Cellulitis of right external ear
H60.12	Cellulitis of left external ear
H60.13	Cellulitis of external ear, bilateral
K12.2	Cellulitis and abscess of mouth
L03	Cellulitis and acute lymphangitis
L03.0	Cellulitis and acute lymphangitis of finger and toe
L03.01	Cellulitis of finger
L03.011	Cellulitis of right finger
L03.012	Cellulitis of left finger
L03.019	Cellulitis of unspecified finger
L03.03	Cellulitis of toe
L03.031	Cellulitis of right toe
L03.032	Cellulitis of left toe
L03.039	Cellulitis of unspecified toe
L03.1	Cellulitis and acute lymphangitis of other parts of limb
L03.11	Cellulitis of other parts of limb
L03.111	Cellulitis of right axilla
L03.112	Cellulitis of left axilla
L03.113	Cellulitis of right upper limb
L03.114	Cellulitis of left upper limb
L03.115	Cellulitis of right lower limb
L03.116	Cellulitis of left lower limb
L03.119	Cellulitis of unspecified part of limb
L03.2	Cellulitis and acute lymphangitis of face and neck
L03.21	Cellulitis and acute lymphangitis of face
L03.211	Cellulitis of face
L03.22	Cellulitis and acute lymphangitis of neck
L03.221	Cellulitis of neck
L03.3	Cellulitis and acute lymphangitis of trunk
L03.31	Cellulitis of trunk
L03.311	Cellulitis of abdominal wall
L03.312	Cellulitis of back [any part except buttock]
L03.313	Cellulitis of chest wall
L03.314	Cellulitis of groin
L03.315	Cellulitis of perineum
L03.316	Cellulitis of umbilicus
L03.317	Cellulitis of buttock
L03.319	Cellulitis of trunk, unspecified
L03.8	Cellulitis and acute lymphangitis of other sites
L03.81	Cellulitis of other sites
L03.811	Cellulitis of head [any part, except face]
L03.818	Cellulitis of other sites
L03.9	Cellulitis and acute lymphangitis, unspecified
L03.90	Cellulitis, unspecified
L08.9	Local infection of the skin and subcutaneous tissue, unspecified
N48.22	Cellulitis of corpus cavernosum and penis
Skin and skin structure klebsiella infection
B96.1	Klebsiella pneumoniae [k. pneumoniae] as the cause of diseases classified elsewhere
L08.9	Local infection of the skin and subcutaneous tissue, unspecified
Staphylococcus aureus skin and skin structure infection
B95.6	Staphylococcus aureus as the cause of diseases classified elsewhere
H60.1	Cellulitis of external ear
H60.10	Cellulitis of external ear, unspecified ear
H60.11	Cellulitis of right external ear
H60.12	Cellulitis of left external ear
H60.13	Cellulitis of external ear, bilateral
J34.0	Abscess, furuncle and carbuncle of nose
L02	Cutaneous abscess, furuncle and carbuncle
L02.0	Cutaneous abscess, furuncle and carbuncle of face
L02.02	Furuncle of face
L02.03	Carbuncle of face
L02.1	Cutaneous abscess, furuncle and carbuncle of neck
L02.12	Furuncle of neck
L02.13	Carbuncle of neck
L02.2	Cutaneous abscess, furuncle and carbuncle of trunk
L02.22	Furuncle of trunk
L02.221	Furuncle of abdominal wall
L02.222	Furuncle of back [any part, except buttock]
L02.223	Furuncle of chest wall
L02.224	Furuncle of groin
L02.225	Furuncle of perineum
L02.226	Furuncle of umbilicus
L02.229	Furuncle of trunk, unspecified
L02.23	Carbuncle of trunk
L02.231	Carbuncle of abdominal wall
L02.232	Carbuncle of back [any part, except buttock]
L02.233	Carbuncle of chest wall
L02.234	Carbuncle of groin
L02.235	Carbuncle of perineum
L02.236	Carbuncle of umbilicus
L02.239	Carbuncle of trunk, unspecified
L02.3	Cutaneous abscess, furuncle and carbuncle of buttock
L02.32	Furuncle of buttock
L02.33	Carbuncle of buttock
L02.4	Cutaneous abscess, furuncle and carbuncle of limb
L02.42	Furuncle of limb
L02.421	Furuncle of right axilla
L02.422	Furuncle of left axilla
L02.423	Furuncle of right upper limb
L02.424	Furuncle of left upper limb
L02.425	Furuncle of right lower limb
L02.426	Furuncle of left lower limb
L02.429	Furuncle of limb, unspecified
L02.43	Carbuncle of limb
L02.431	Carbuncle of right axilla
L02.432	Carbuncle of left axilla
L02.433	Carbuncle of right upper limb
L02.434	Carbuncle of left upper limb
L02.435	Carbuncle of right lower limb
L02.436	Carbuncle of left lower limb
L02.439	Carbuncle of limb, unspecified
L02.5	Cutaneous abscess, furuncle and carbuncle of hand
L02.52	Furuncle hand
L02.521	Furuncle right hand
L02.522	Furuncle left hand
L02.529	Furuncle unspecified hand
L02.53	Carbuncle of hand
L02.531	Carbuncle of right hand
L02.532	Carbuncle of left hand
L02.539	Carbuncle of unspecified hand
L02.6	Cutaneous abscess, furuncle and carbuncle of foot
L02.62	Furuncle of foot
L02.621	Furuncle of right foot
L02.622	Furuncle of left foot
L02.629	Furuncle of unspecified foot
L02.63	Carbuncle of foot
L02.631	Carbuncle of right foot
L02.632	Carbuncle of left foot
L02.639	Carbuncle of unspecified foot
L02.8	Cutaneous abscess, furuncle and carbuncle of other sites
L02.82	Furuncle of other sites
L02.821	Furuncle of head [any part, except face]
L02.828	Furuncle of other sites
L02.83	Carbuncle of other sites
L02.831	Carbuncle of head [any part, except face]
L02.838	Carbuncle of other sites
L02.9	Cutaneous abscess, furuncle and carbuncle, unspecified
L02.92	Furuncle, unspecified
L02.93	Carbuncle, unspecified
L03.01	Cellulitis of finger
L03.011	Cellulitis of right finger
L03.012	Cellulitis of left finger
L03.019	Cellulitis of unspecified finger
L03.03	Cellulitis of toe
L03.031	Cellulitis of right toe
L03.032	Cellulitis of left toe
L03.039	Cellulitis of unspecified toe
L03.1	Cellulitis and acute lymphangitis of other parts of limb
L03.11	Cellulitis of other parts of limb
L03.111	Cellulitis of right axilla
L03.112	Cellulitis of left axilla
L03.113	Cellulitis of right upper limb
L03.114	Cellulitis of left upper limb
L03.115	Cellulitis of right lower limb
L03.116	Cellulitis of left lower limb
L03.119	Cellulitis of unspecified part of limb
L03.2	Cellulitis and acute lymphangitis of face and neck
L03.21	Cellulitis and acute lymphangitis of face
L03.211	Cellulitis of face
L03.22	Cellulitis and acute lymphangitis of neck
L03.221	Cellulitis of neck
L03.3	Cellulitis and acute lymphangitis of trunk
L03.31	Cellulitis of trunk
L03.311	Cellulitis of abdominal wall
L03.312	Cellulitis of back [any part except buttock]
L03.313	Cellulitis of chest wall
L03.314	Cellulitis of groin
L03.315	Cellulitis of perineum
L03.316	Cellulitis of umbilicus
L03.317	Cellulitis of buttock
L03.319	Cellulitis of trunk, unspecified
L03.8	Cellulitis and acute lymphangitis of other sites
L03.81	Cellulitis of other sites
L03.811	Cellulitis of head [any part, except face]
L03.818	Cellulitis of other sites
L03.9	Cellulitis and acute lymphangitis, unspecified
L03.90	Cellulitis, unspecified
L08.89	Other specified local infections of the skin and subcutaneous tissue
L08.9	Local infection of the skin and subcutaneous tissue, unspecified
N48.22	Cellulitis of corpus cavernosum and penis
Upper respiratory infection
J00	Acute nasopharyngitis [common cold]
J01	Acute sinusitis
J01.0	Acute maxillary sinusitis
J01.00	Acute maxillary sinusitis, unspecified
J01.01	Acute recurrent maxillary sinusitis
J01.1	Acute frontal sinusitis
J01.10	Acute frontal sinusitis, unspecified
J01.11	Acute recurrent frontal sinusitis
J01.2	Acute ethmoidal sinusitis
J01.20	Acute ethmoidal sinusitis, unspecified
J01.21	Acute recurrent ethmoidal sinusitis
J01.3	Acute sphenoidal sinusitis
J01.30	Acute sphenoidal sinusitis, unspecified
J01.31	Acute recurrent sphenoidal sinusitis
J01.4	Acute pansinusitis
J01.40	Acute pansinusitis, unspecified
J01.41	Acute recurrent pansinusitis
J01.8	Other acute sinusitis
J01.80	Other acute sinusitis
J01.81	Other acute recurrent sinusitis
J01.9	Acute sinusitis, unspecified
J01.90	Acute sinusitis, unspecified
J01.91	Acute recurrent sinusitis, unspecified
J02	Acute pharyngitis
J02.0	Streptococcal pharyngitis
J02.8	Acute pharyngitis due to other specified organisms
J02.9	Acute pharyngitis, unspecified
J03	Acute tonsillitis
J03.0	Streptococcal tonsillitis
J03.00	Acute streptococcal tonsillitis, unspecified
J03.01	Acute recurrent streptococcal tonsillitis
J03.8	Acute tonsillitis due to other specified organisms
J03.80	Acute tonsillitis due to other specified organisms
J03.81	Acute recurrent tonsillitis due to other specified organisms
J03.9	Acute tonsillitis, unspecified
J03.90	Acute tonsillitis, unspecified
J03.91	Acute recurrent tonsillitis, unspecified
J04	Acute laryngitis and tracheitis
J04.0	Acute laryngitis
J04.1	Acute tracheitis
J04.10	Acute tracheitis without obstruction
J04.11	Acute tracheitis with obstruction
J04.2	Acute laryngotracheitis
J04.3	Supraglottitis, unspecified
J04.30	Supraglottitis, unspecified, without obstruction
J04.31	Supraglottitis, unspecified, with obstruction
J05	Acute obstructive laryngitis [croup] and epiglottitis
J05.0	Acute obstructive laryngitis [croup]
J05.1	Acute epiglottitis
J05.10	Acute epiglottitis without obstruction
J05.11	Acute epiglottitis with obstruction
J06	Acute upper respiratory infections of multiple and unspecified sites
J06.0	Acute laryngopharyngitis
J06.9	Acute upper respiratory infection, unspecified