Amoxicillin + Clavulanic Acid + Lactobacillus: Uses & Safety

Amoxicillin 500mg + Clavulanic Acid 125mg + Lactic Acid (Lactobacillus) 60M is an oral antibacterial combination that also carries a probiotic ingredient. Amoxicillin, printed as amoxycillin on many Indian labels, is a penicillin-class antibacterial. Clavulanic acid is supplied as potassium clavulanate and shields amoxicillin from bacterial defence enzymes; the two salts together are commonly called co-amoxiclav. Lactic acid bacillus is a spore-forming, lactic-acid-producing bacterium, and 60M means 60 million spores in the tablet [6][7]. Doctors prescribe combinations of this type for bacterial infections of the sinuses, ears, throat, chest, skin and urinary tract. The lactic acid bacillus is included for adults prone to antibiotic-associated diarrhoea, meaning loose stools brought on by the antibiotic itself.

This combination puts three ingredients to work on three different jobs. Amoxicillin is a semisynthetic antibacterial built on the basic penicillin nucleus, 6-aminopenicillanic acid. It kills bacteria rather than only slowing their growth. Many bacteria defend themselves with beta-lactamase enzymes, which break amoxicillin apart before it can act. Clavulanic acid, produced by fermentation of Streptomyces clavuligerus, blocks the working sites of several of those enzymes. The US prescribing information says this pairing "extends the antibacterial spectrum of amoxicillin to include many bacteria normally resistant to amoxicillin", covering beta-lactamase-producing strains of Staphylococcus aureus, Escherichia coli, Klebsiella species, Haemophilus influenzae, Moraxella catarrhalis and Enterobacter species [1]. India's Central Drugs Standard Control Organisation records approval of Amoxycillin 500mg with Clavulanic Acid 125mg film-coated tablets on 06.01.1995 [6].

The third ingredient targets a predictable side effect rather than the infection. Antibacterial treatment alters the normal flora of the colon, and diarrhoea or loose stools were the most frequently reported adverse reaction in trials, at 9% [1]. Indian packs often print this ingredient as Lactobacillus, but the organism in lactic acid bacillus products belongs to the genus Bacillus. CDSCO records it as "lactic acid bacillus (lactobacillus sporogenes)" [6], and the US National Library of Medicine indexes Lactobacillus sporogenes as an alternative name for Bacillus coagulans, which it describes as a lactic-acid-producing species of Bacillus used as a probiotic [7][8]. Bacillus species form endospores, so this ingredient is supplied and counted as spores [9]. The US National Center for Complementary and Integrative Health reports that a 2017 review found giving probiotics along with antibiotics "was associated with a decrease of about half in the likelihood of antibiotic-associated diarrhea", while calling that conclusion tentative because the quality of the studies was only moderate [5].

This combination needs medical supervision. It acts only on bacteria and does nothing for viral illness such as the common cold or flu [2]. A doctor decides whether it suits your infection, your kidney and liver function, and your allergy history.

The CDSCO approval for the amoxycillin with clavulanic acid tablet lists these infections [6]:

• Sinusitis, infection of the air spaces around the nose.
• Otitis media, a middle ear infection.
• Tonsillitis, infection of the tonsils at the back of the throat.
• Acute and chronic bronchitis, chest infection affecting the breathing tubes.
• Skin and soft tissue infections, such as infected wounds and boils.
• Pelvic infections, bacterial infections of the organs low in the abdomen.
• Osteomyelitis, a bone infection.

The US prescribing information adds two more [1]:

• Lower respiratory tract infections caused by beta-lactamase-producing Haemophilus influenzae and Moraxella catarrhalis.
• Urinary tract infections caused by beta-lactamase-producing E. coli, Klebsiella species and Enterobacter species.

The lactic acid bacillus component has a separate purpose:

• Reducing the chance of antibiotic-associated diarrhoea, which is why CDSCO has cleared amoxicillin-with-lactobacillus products for adults prone to it [6].

Take the tablet by mouth exactly as prescribed. The US label advises that each dose be taken with a meal or snack to reduce the possibility of stomach upset, and that doses are given every 8 hours or every 12 hours depending on what has been prescribed [1].

Do not swap strengths or forms on your own. The ratio of the two salts differs between products, and the label states that two 250 mg/125 mg tablets are not substitutable with one 500 mg/125 mg tablet [1].

Finish the full course even if you feel better within a few days. The label counsels that skipping doses or not completing the course may reduce the effectiveness of the treatment and increase the likelihood that bacteria develop resistance [1]. The World Health Organization states that the misuse and overuse of antimicrobials are driving the development and spread of drug-resistant pathogens [10].

1. Protection against bacterial defences. Clavulanic acid binds to the working site of beta-lactamase enzymes so they cannot destroy amoxicillin [4].
2. Wider coverage than amoxicillin alone. The pair reaches beta-lactamase-producing bacteria that amoxicillin alone cannot [1].
3. Gut support in the same tablet. The lactic acid bacillus is included to reduce the chance of loose stools during the course. Evidence for probiotics alongside antibiotics is encouraging but not firm, and NCCIH describes the supporting review as tentative [5].
4. Schedule flexibility. The label lists the 500 mg/125 mg strength at both every 8 hours and every 12 hours, so a prescriber can match the schedule to the infection [1].

All figures below come from the US prescribing information [1].

Common Side Effects (Usually Mild and may lessen with continued use)

• Diarrhoea or loose stools, reported in 9% of patients in clinical trials
• Nausea (3%) and vomiting (1%)
• Skin rashes and urticaria, meaning raised itchy hives (3%)
• Vaginitis, that is irritation of the vagina with itching or discharge (1%)
• Abdominal discomfort, wind and headache, each under 1%
• Indigestion, mouth soreness or a black "hairy" tongue, reported after marketing

Serious Side Effects (Seek Urgent Medical Attention)

• Swelling of the face or throat, difficulty breathing, or collapse
• Skin that blisters or peels, or sores inside the mouth, which can signal the severe skin and allergic reactions the label lists as SJS and TEN (Stevens-Johnson syndrome and toxic epidermal necrolysis), DRESS and AGEP
• Watery or bloody stools with cramps or fever, which the label notes can appear over 2 months after antibacterial treatment and may mean Clostridioides difficile associated diarrhoea, a serious bowel infection
• Yellow skin or eyes, dark urine or pain high on the right side of the abdomen, suggesting liver trouble such as cholestatic jaundice, in which bile flow slows and the skin or eyes turn yellow
• Repeated vomiting 1 to 4 hours after a dose with paleness or unusual sleepiness, described in the label as drug-induced enterocolitis syndrome
• Cloudy or bloody urine, or passing much less urine than usual

Swallow the film-coated tablet whole with a glass of plain water, and space the doses evenly through the day, at least 4 hours apart, as NHS guidance on co-amoxiclav advises [3]. Steady gaps matter because amoxicillin works best when blood levels stay above the minimum inhibitory concentration, the lowest drug level that stops the bacteria growing, for as long as possible [4]. Keep the same food pattern at every dose through the course, and if swallowing tablets is difficult, tell your doctor rather than altering the tablet.

Amoxicillin binds to penicillin-binding proteins, the bacterial enzymes that stitch the cell wall together, and blocks transpeptidation, the cross-linking step of wall building. That switches on the bacterium's own autolytic enzymes, so the wall breaks open and the cell dies. The killing is bactericidal and time-dependent, meaning what counts is how long drug levels stay above the minimum inhibitory concentration [4].

Clavulanic acid contributes little antibacterial strength of its own. It is a beta-lactam related to the penicillins, and it binds to the working site of beta-lactamase enzymes, shielding amoxicillin from breakdown [1][4].

Lactic acid bacillus acts in the gut rather than at the infection site. It is swallowed as live spores of a lactic-acid-producing Bacillus, and probiotics of this type are taken to support the gut flora that antibacterial treatment disturbs [5][7][9].

Blood levels peak about 1.5 hours after a tablet dose, and both salts are cleared mainly by the kidneys within a few hours [1].

• Pregnancy — Animal studies showed no evidence of harm to the foetus, but there are no adequate and well-controlled studies in pregnant women, so the label says to use during pregnancy only if clearly needed [1]. NHS guidance states you can usually take co-amoxiclav in pregnancy if your doctor thinks you need it [3].
• Breastfeeding — Amoxicillin passes into human milk and use by nursing mothers may lead to sensitisation of infants, so the label advises caution [1]. NHS guidance states you can usually take co-amoxiclav while breastfeeding, but check with a pharmacist or doctor first [3].
• Alcohol — NHS guidance does not set an alcohol restriction for co-amoxiclav [3]. Because this combination has been linked to liver problems, tell your doctor how much you usually drink, especially if you have liver disease [1].
• Driving — NHS guidance states co-amoxiclav will not usually affect driving, cycling or using machinery, but that you should not do those things while you feel dizzy after a dose [3].
• Kidney / Renal Impairment — The label states that patients with a glomerular filtration rate, a blood test of how well the kidneys filter, below 30 mL/min should not receive the 875 mg strength, and that dosage adjustment is recommended in severe kidney impairment [1].
• Liver / Hepatic Impairment — Hepatitis and cholestatic jaundice, a liver problem in which bile flow slows and the skin or eyes turn yellow, have been associated with this combination, reported more commonly in older people, in males and in patients on prolonged treatment. The label advises that liver function be monitored at regular intervals in people with liver impairment [1].
• Diet / Food — The label advises taking each dose at the start of a meal, since clavulanate is absorbed better with food and stomach upset is less likely [1]. NHS guidance states you can eat as normal while taking co-amoxiclav [3].
• Lifestyle / Children / Elderly — In a pooled analysis of 3,119 patients, 32% were 65 or older and 14% were 75 or older, with no overall differences in safety or effectiveness observed [1]. NCCIH notes that the risk from probiotics is greater in people who are severely ill or have a weakened immune system, and that severe or fatal infections have been reported in premature infants given probiotics [5].

• Take each dose with plain water at the start of a meal or snack.
• Tell your doctor before the first dose about any past reaction to penicillins or cephalosporins.
• Keep the same dosing times every day, and set a reminder if your schedule is every 8 hours.
• Complete the prescribed course even after symptoms settle.
• Drink fluids normally through the course.
• Report any new rash straight away rather than waiting to see if it spreads.

Store tablets at 20 to 25 degrees C (68 to 77 degrees F), described in the label as USP Controlled Room Temperature [1]. Keep them in the container they came in, tightly closed and out of reach of children, away from excess heat and moisture, and not in the bathroom [2]. If an oral suspension is prescribed instead, the label states that reconstituted suspension is kept refrigerated and discarded after 10 days [1]. Keep all medicines away from children and pets.

Food matters mainly for the clavulanate component. The label states the combination may be taken without regard to meals, that clavulanate absorption is greater with food than on an empty stomach, and that dosing at the start of a meal reduces stomach intolerance. The same label records that the relative bioavailability of clavulanate, meaning how much reaches the bloodstream, fell when dosing followed the start of a high-fat breakfast by 30 and 150 minutes [1].

• Probenecid (a gout medicine): slows the kidneys' removal of amoxicillin, raising and prolonging blood levels. The label states coadministration is not recommended [1].
• Allopurinol (another gout medicine): taken with amoxicillin, it increases the risk of rash [1].
• Oral anticoagulants such as warfarin: the label reports abnormal lengthening of the prothrombin time, a blood-clotting test also reported as INR, so monitoring is advised [1].
• Combined oral contraceptives: effects on gut flora may lower estrogen reabsorption and reduce how well the pill works [1].
• Methotrexate: NHS guidance lists methotrexate among medicines that may not mix well with co-amoxiclav [3].
• Laboratory tests: high urine levels of amoxicillin can give false-positive urine glucose results with CLINITEST, Benedict's Solution or Fehling's Solution, so the label recommends glucose tests based on enzymatic glucose oxidase reactions [1].

• Previous serious allergic reaction to amoxicillin, clavulanate or other beta-lactam medicines such as penicillins and cephalosporins is a contraindication [1].
• Past cholestatic jaundice or liver dysfunction linked to amoxicillin with clavulanate is also a contraindication [1].
• Infectious mononucleosis, also called glandular fever: a high proportion of these patients develop a red rash, and the label states the combination should not be given to them [1]. NHS guidance asks you to tell your doctor if you have or think you may have glandular fever [3].
• Severe kidney impairment: high blood levels occur more readily as kidney clearance falls, and interstitial nephritis, meaning kidney inflammation, has been reported after overdosage [1].
• Severe illness or a weakened immune system: NCCIH advises caution with probiotics in seriously ill hospitalised patients and in premature infants [5].

For adults and children weighing 40 kg or more, the US label describes amoxicillin and clavulanate regimens of 500 mg or 875 mg every 12 hours, or 250 mg or 500 mg every 8 hours, counted on the amoxicillin component and chosen by the severity of the infection. The 500 mg/125 mg tablet appears in that label at both every 12 hours and every 8 hours [1]. Your prescriber sets your dose, frequency and course length. Take only what has been prescribed, and do not adjust it yourself.

Possible signs include vomiting, abdominal pain, drowsiness, cloudy or bloody urine and reduced urine output. The label reports interstitial nephritis, meaning kidney inflammation, leading to kidney failure with very little urine passed, and crystalluria, drug crystals in the urine, which has in some cases led to kidney failure. It states that in case of overdosage adequate fluid intake and urine flow should be maintained to reduce that risk. A study of 51 paediatric patients at a poison-control centre suggested that overdosages below 250 mg/kg of amoxicillin are not associated with significant clinical symptoms. Treatment is supportive, and the drug can be removed by haemodialysis [1]. If an overdose is suspected, contact your doctor or the nearest emergency department immediately and carry the pack with you.

Take the missed dose as soon as you remember. If it is almost time for the next dose, skip the one you missed and continue your regular schedule. Do not take a double dose to make up for a missed one [2]. If you keep missing doses, tell your doctor, because gaps in an antibacterial course can reduce how well it works [1].

• Trouble breathing, wheezing, or swelling of the lips, tongue, face or throat
• Any rash, hives, mouth ulcers, blistering or peeling skin
• Severe or persistent diarrhoea, or watery or bloody stools during or after the course
• Yellow eyes or skin, dark urine, pale stools or pain high on the right of the abdomen
• Severe or repeated vomiting after a dose, with paleness, sleepiness or faintness
• Passing much less urine than usual, or cloudy or bloody urine
• Fever with joint pain and rash, which the label links to a serum sickness-like reaction (a delayed allergic reaction)

• Therapeutic Class — Anti-infective (systemic antibacterial) with a probiotic component
• Action Class — Penicillin-class bactericidal antibacterial plus beta-lactamase inhibitor, with live lactic-acid-producing spores
• Chemical Class — Amoxicillin: beta-lactam built on the 6-aminopenicillanic acid nucleus. Clavulanic acid: beta-lactam beta-lactamase inhibitor from Streptomyces clavuligerus. Lactic acid bacillus: a spore-forming, lactic-acid-producing bacterium, recorded by CDSCO as lactic acid bacillus (Lactobacillus sporogenes) and indexed by the US National Library of Medicine under Bacillus coagulans
• Habit Forming — No