Antibiotics Flashcards

Question

What are the route of administration for aminoglycosides and their pharmacokinetic profiles?

Answer 1

* Not absorbed from GUT so must be given via injections (IV/IM) * Gentamycin most common choice * Majority excreted by kidneys, small amount in bile * MUST MONITOR GENTAMYCIN

Answer 2

_Unwanted side effects:_ * Nephrotoxicity * Ototoxicity * Skin reactions * Tinnitus

Answer 3

[Neomycin sulfate](https://bnf.nice.org.uk/drugs/neomycin-sulfate/) is too toxic for parenteral administration and can only be used for infections of the skin or mucous membranes or to reduce the bacterial population of the colon prior to bowel surgery or in hepatic failure. Oral administration may lead to malabsorption. Small amounts of [neomycin sulfate](https://bnf.nice.org.uk/drugs/neomycin-sulfate/) may be absorbed from the gut in patients with hepatic failure and, as these patients may also be uraemic, cumulation may occur with resultant ototoxicity.

Answer 4

_Cautions_ * Muscle weakness, renal impairment? * Used with caution in premature infants because of their renal immaturity. Elderly, impaired renal function, diabetes, auditory vestibular dysfunctions, otitis media. * history of otitis media, previous use of ototoxic drugs and a genetically determined high sensitivity to aminoglycoside induced ototoxicity, are other main factors which may pre-dispose the patient to toxicity. _Contra-indications_ * Myasthenia Gravis * Hypersensitivity to aminoglycoside

Answer 5

(i) Antibacterials: increased risk of nephrotoxicity with cephalosporins notably cephalothin. (ii) Gentamicin has been known to potentiate anticoagulants such as warfarin and phenindione. (iii) Antifungals: increased risk of nephrotoxicity with amphotericin B. (iv) Cholinergics: antagonism of effect of neostigmine and pyridostigmine. (v) Cyclosporin, cisplatin: increased risk of nephrotoxicity. (vi) Cytotoxics: increased risk of nephrotoxicity and possible risk of ototoxicity with cisplatin. (vii) Diuretics: increased risk of ototoxicity with loop diuretics. (viii) Muscle relaxants: effect of non-depolarising muscle relaxants such as tubocurarine enhanced. Neuromuscular blockade and respiratory paralysis have been reported from administration of aminoglycosides to patients who have received curare-type muscle relaxants during anaesthesia.

Answer 6

1. Sulfamethoxazole and trimethoprim 2. Sulphonamides

Answer 7

1. It is effective against most gram-positive aerobic cocci and some gram-negative aerobic bacilli 2. Effective against gram positive and negative **3. The combination of TMP-SMX is active against most aerobic gram-positive and gram-negative organisms**.

Answer 8

Co-Trimoxazole tablets are indicated in children (\>12 to \<18 years old) and adults (\>18 years old) for the treatment of the following infections when owing to sensitive organisms (see section 5.1): * Treatment and prevention of *Pneumocystis jirovecii* pneumonitis or “PJP”. * Treatment and prophylaxis of toxoplasmosis. * Treatment of nocardiosis. The following infections may be treated with Co-Trimoxazole where there is bacterial evidence of sensitivity to Co-Trimoxazole and good reason to prefer the combination of antibiotics in Co-Trimoxazole to a single antibiotic: * Acute uncomplicated urinary tract infection. * Acute otitis media. * Acute exacerbation of chronic bronchitis. Consideration should be given to official guidance on the appropriate use of antibacterial agents.

Answer 9

* 50% protein bound * Renal excretion primarily

Answer 10

_Unwanted side-effects:_ Co-trimoxazole is associated with rare but serious side effects. Discontinue immediately if **blood disorders** (including leucopenia, thrombocytopenia, megaloblastic anaemia, eosinophilia) or **rash** (including Stevens-Johnson syndrome or toxic epidermal necrolysis) develop. Severe respiratory toxicity including potential progression to Adult Respiratory Distress Syndrome. _Common:_ Diarrhoea; electrolyte imbalance; fungal overgrowth; headache; nausea; skin reactions, hyperkalaemia NICE: * **Blood disorders (including leucopenia, thrombocytopenia, anaemia, and eosinophilia)** are rare but serious adverse effects of co-trimoxazole. * Discontinue treatment with co-trimoxazole immediately if blood disorders develop. * **Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS),** have been rarely reported with co-trimoxazole. * Advise people taking co-trimoxazole to monitor closely for skin reactions. The highest risk for occurrence of SJS, TEN, or DRESS is within the first weeks of treatment. * If symptoms or signs of SJS, TEN, or DRESS (for example progressive skin rash often with blisters or mucosal lesions) occur, discontinue treatment with co-trimoxazole. * If a person develops SJS or TEN with the use of co-trimoxazole, co-trimoxazole must not be re-started at any time.

Answer 11

* Severe renal impairment - Avoid if eGFR less than 15 mL/minute/1.73 m² and if plasma-sulfamethoxazole concentration cannot be monitored. * Severe hepatic impairment * Acute porphyrias * Severe haematological disorders (Such as blood dyscrasias)

Answer 12

Asthma; avoid in blood disorders (unless under specialist supervision); avoid in infants under 6 weeks (except for treatment or prophylaxis of pneumocystis pneumonia) because of the risk of kernicterus; elderly (increased risk of serious side-effects) (in adults); G6PD deficiency (risk of haemolytic anaemia); maintain adequate fluid intake; predisposition to folate deficiency; predisposition to hyperkalaemia

Answer 13

Potential drug interactions: hyperkalaemia agents (e.g. K+ sparing diuretics, ACEi, ARBs), bone marrow depressants (trimethoprim is an immunosupressant), cytotoxic agents e.g. azathioprine, mercaptopurine, methotrexate (increased risk of haematologic toxicity). * **Interactions with co-trimoxazole (trimethoprim/sulfamethoxazole) include:** * **Digoxin** — concurrent use of trimethoprim with digoxin has been shown to increase plasma digoxin levels in some elderly people. * If there are symptoms of digoxin toxicity (for example, nausea, anorexia, or disturbance of colour vision), check serum digoxin levels. * **Diuretics** — in elderly people concurrently receiving diuretics, mainly thiazides, there appears to be an increased risk of thrombocytopenia with or without purpura. * Manufacturer makes no recommendation. * **Drugs that can cause hyperkalaemia** (for example angiotensin-converting enzyme [ACE] inhibitors, angiotensin receptor blockers, and diuretics) — concurrent use with co-trimoxazole may result in clinically significant hyperkalaemia. * Concurrent use should be done cautiously. * **Methotrexate** — co-trimoxazole may increase free plasma levels of methotrexate. In addition, methotrexate and trimethoprim are both anti-folate drugs. * Avoid concurrent use with co-trimoxazole. * If co-trimoxazole treatment is necessary, a folate supplement should be considered. * **Phenytoin** — co-trimoxazole may prolong the half-life of phenytoin, resulting in increased serum phenytoin levels. * If symptoms of phenytoin toxicity (confusion, blurred vision, nystagmus, ataxia, or drowsiness) are present, monitor serum phenytoin levels and reduce the dose if necessary. * **Warfarin** — concurrent treatment with co-trimoxazole may increase the anticoagulant effect of warfarin. * Monitor the international normalized ratio (INR), and adjust the warfarin dose accordingly. * **Oral hormonal contraception** — additional contraceptive precautions are not required during or after a course of co-trimoxazole [[FSRH, 2017](https://cks.nice.org.uk/topics/leg-ulcer-venous/references/)]. * However, advise women on the importance of correct contraceptive practice if they experience vomiting or diarrhoea. For further information, see the section on vomiting or diarrhoea in the CKS topics on [Contraception - combined hormonal methods](https://cks.nice.org.uk/topics/contraception-combined-hormonal-methods/) and [Contraception - progestogen-only methods](https://cks.nice.org.uk/topics/contraception-progestogen-only-methods/). * _Azathioprine:_ There are conflicting clinical reports of interactions between azathioprine and trimethoprim-sulfamethoxazole, resulting in serious haematological abnormalities.

Answer 14

Trimethoprim is a dihydrofolate reductase inhibitor. It works by inhibiting DHR from reducing THF (tetrahydrofolate acid) to DHF (Dihydrofolate acid). DHF is an important precursor is pyrimidine and purine synthesis important for DNA synthesis – this ultimately prevents multiplication

Answer 15

Sulfamethoxazole competitively inhibits dihydropteroate synthase, the enzyme responsible for bacterial conversion of PABA to dihydrofolic acid. Inhibition of this pathway prevents the synthesis of tetrahydrofolate and, ultimately, the synthesis of bacterial purines and DNA, resulting in a bacteriostatic effect.

Answer 16

Sulfamethoxazole competitively inhibits dihydropteroate synthase, the enzyme responsible for bacterial conversion of PABA to dihydrofolic acid. Inhibition of this pathway prevents the synthesis of tetrahydrofolate and, ultimately, the synthesis of bacterial purines and DNA, resulting in a bacteriostatic effect.

Answer 17

[ciprofloxacin](https://bnf.nice.org.uk/drugs/ciprofloxacin/), [delafloxacin](https://bnf.nice.org.uk/drugs/delafloxacin/), [levofloxacin](https://bnf.nice.org.uk/drugs/levofloxacin/), [moxifloxacin](https://bnf.nice.org.uk/drugs/moxifloxacin/), and [ofloxacin](https://bnf.nice.org.uk/drugs/ofloxacin/)

Answer 18

They exert their actions by inhibiting bacterial nucleic acid synthesis through disrupting the enzymes topoisomerase IV and DNA gyrase, and by causing breakage of bacterial chromosomes

Answer 19

The drug should be discontinued if **neurological, psychiatric, tendon disorders** or **hypersensitivity reactions** (including severe rash) occur. For more information regarding the safety of fluoroquinolones, please see Important Safety Information. Important Side-effects: * QT inteveral Prolongation * Tendon damage * Hypersensivity reactions (SCARs - severe cutaneous adverse reactions) * **Gastrointestinal** — diarrhoea, nausea (common), vomiting, dyspepsia, flatulence, gastrointestinal and abdominal pains (uncommon). * **Rarely**: pseudomembranous colitis (for more information, see the CKS topic on [Diarrhoea - antibiotic associated](https://cks.nice.org.uk/topics/diarrhoea-antibiotic-associated/)). * **Musculoskeletal** — pain, arthralgia (uncommon). * **Rarely:** myalgia, arthritis. * **Very rarely**: muscle weakness, tendonitis, tendon damage — this may occur within 48 hours of starting treatment, or months after stopping. Risk of tendon rupture is increased by co-administration of corticosteroids and in people aged over 60 years. If tendonitis is suspected, ciprofloxacin should be discontinued immediately. * **Nervous system** — headache, dizziness, sleep disorders, taste disorders (uncommon). * **Rarely**: tremor, vertigo, lowering of the seizure threshold – this may trigger seizures. * **Psychiatric** — hyperactivity, agitation (uncommon). * **Rarely**: confusion, anxiety, depression, hallucinations. * **Skin** — rash, pruritus, urticaria. * **Rarely:** Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis anaphylaxis, drug rash with eosinophilia, systemic symptoms (DRESS), acute generalised exanthematous pustulosis (AGEP). * **Cardiovascular system** — there is an increased risk of aortic aneurysm and dissection with fluoroquinolones, particularly in the older population. Fluoroquinolones should only be used after careful benefit-risk assessment and after consideration of other therapeutic options in people with positive family history of aneurysm disease, or in people diagnosed with pre-existing aortic aneurysm and/or aortic dissection, or in presence of other risk factors or conditions predisposing for aortic aneurysm and dissection (for example, Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, giant cell arteritis, Behcet’s disease, hypertension, known atherosclerosis). * **Other adverse effects include:** * Anaphylaxis. * Hepatic impairment, hepatitis. * Renal impairment. * Tachycardia. * Tinnitus. * Visual disturbances. * **NOTE:** fluoroquinolones can very rarely cause long-lasting (up to months or years), disabling, and potentially irreversible side effects, sometimes affecting multiple systems, organ classes, and senses. People should be advised to stop treatment at the first signs of a serious adverse reaction, such as tendonitis or tendon rupture, muscle pain, muscle weakness, joint pain, joint swelling, peripheral neuropathy, and central nervous system effects, and to contact their doctor immediately for further advice

Answer 20

* History of tendon disorders related to quinolone use

Answer 21

* Prolong QT interval * Risk factors for QT intevral - bradycardia, electrolyte disturbance) * Conditions that predispose to seizures * diabetes (may affect glucose) * Expose to excessive sunlight/UV radiation should be avoided during and 48h after treatment * G6PD deficiency * history of epilepsy * myasthenia gravis (Risk of exacerbation) * psychiatric disorders NICE: * * Positive family history of aneurysm disease or congenital heart valve disease. * Pre-existing aortic aneurysm and/or dissection or heart valve disease, or in presence of other risk factors or conditions predisposing for: * Both aortic aneurysm and dissection and heart valve regurgitation/incompetence (e.g. connective tissue disorders such as Marfan syndrome or Ehlers-Danlos syndrome, Turner syndrome, Behcet's disease, hypertension, rheumatoid arthritis) *or additionally* * Aortic aneurysm and dissection (such as vascular disorders including Takayasu arteritis or giant cell arteritis, or known atherosclerosis, or Sjögren's syndrome) *or additionally* * Heart valve regurgitation/incompetence (such as infective endocarditis). * Epilepsy, or conditions that predispose to seizures, and in people taking other medication that may predispose to seizures, as quinolones can lower the seizure threshold. * Quinolones may induce convulsions in patients with or without a history of convulsions, and taking NSAIDs at the same time may also induce them. * Diabetes mellitus — may affect blood glucose. Blood glucose should be monitored closely. * Glucose-6-phosphate dehydrogenase deficiency —haemolytic reactions have been reported. * A history of tendonitis — quinolones can very rarely cause tendon damage, and the risk of tendon rupture is increased by co-administration of corticosteroid. * Conditions which predispose to QT interval prolongation: * Congenital long QT syndrome. * Concomitant use of drugs that are known to prolong the QT interval (for example Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, antipsychotics). * Uncorrected electrolyte imbalance (for example hypokalaemia, or hypomagnesaemia). * Cardiac disease (for example, heart failure, myocardial infarction, or bradycardia). * Electrolyte disturbances. * History of a psychotic disorder — there have been reports of suicidal thoughts or self-endangering behaviour after use quinolones. * Myasthenia gravis — symptoms can be exacerbated. * Also prescribe with caution in people aged over 60 years, people with renal impairment or solid-organ transplants, as they are at a higher risk of tendon injury.

Answer 22

Quinolones are broad-spectrum antibiotics that are active against both Gram-positive and Gram-negative bacteria, including **mycobacteria** (can cause leprosy and TB)**, and anaerobes**.

Answer 23

* **Antacids (containing aluminium, calcium, or magnesium) and other medications containing iron or zinc** — these reduce the absorption of ciprofloxacin if taken concurrently. * Ciprofloxacin should be taken at least 2 hours before these preparations, and not less than 4 to 6 hours after them. * **Ciclosporin** — increased concentrations and nephrotoxicity might occur in a small number of patients. * **Corticosteroids** — the risk of tendonitis and tendon rupture is increased in people taking a fluoroquinolone and a corticosteroid. The MHRA advises that concurrent should be avoided. * **Domperidone** — the manufacturer advises that concurrent use with ciprofloxacin should be avoided as it may lead to QT interval prolongation. * **Ergometrine** — levels may be increased, leading to ergotism. Concurrent use is contraindicated. * **Mizolastine** — the manufacturer advises that concurrent use should be avoided. Mizolastine has a weak potential to cause QT interval prolongation in some people and this may be additive to the effects of ciprofloxacin. * **Methotrexate** — plasma levels of methotrexate may be increased. The manufacturer recommends that concurrent use is avoided. * If concurrent use is necessary, monitor methotrexate levels. * **Nonsteroidal anti-inflammatory drugs (NSAIDs)** — possible increased risk of seizures when quinolones are given with NSAIDs. Avoid concurrent use in people with epilepsy or people predisposed to seizures, or monitor them very closely. * **Oral hormonal contraception** — additional contraceptive precautions are not required during or after courses of ciprofloxacin. * However, women should be advised about the importance of correct contraceptive practice if they experience vomiting or diarrhoea. For further information, see the sections on vomiting or diarrhoea in the CKS topics on [Contraception - combined hormonal methods](https://cks.nice.org.uk/topics/contraception-combined-hormonal-methods/) and [Contraception - progestogen-only methods](https://cks.nice.org.uk/topics/contraception-progestogen-only-methods/). * **Phenytoin** — concurrent administration of ciprofloxacin can cause an increase or decrease in serum phenytoin levels. Monitor phenytoin levels. * **Strontium ranelate** — the absorption of quinolones is reduced by strontium ranelate so they should not be given together. * **Theophylline** — ciprofloxacin increases the plasma concentration of theophylline, leading to possible increased risk of convulsions. Monitor theophylline concentration closely. * **Tizanidine** — ciprofloxacin increases the plasma concentration of tizanidine (increased risk of toxicity). Avoid conccurrent use. * **Warfarin** — rarely, ciprofloxacin may enhance the anticoagulant effect, increasing the risk of bleeding. Monitor the international normalised ratio (INR) within 3 to 5 days of starting ciprofloxacin, frequently during and shortly after administration. * **Zolmitriptan** — quinolones increase the plasma concentration of zolmitriptan by inhibiting its metabolism. Manufacturer recommends a maximum dose of 5 mg in 24 hours in people taking a quinolone. * **Drugs that prolong the QT interval** (such as Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, and antipsychotics) — very rare cases of QT interval prolongation have been reported in people taking quinolones and they should therefore be prescribed with caution alongside drugs known to prolong the QT interval.

Answer 24

[https://assets.publishing.service.gov.uk/media/5c9364c6e5274a48edb9a9fa/FQ-patient-sheet-final.pdf](https://assets.publishing.service.gov.uk/media/5c9364c6e5274a48edb9a9fa/FQ-patient-sheet-final.pdf)

Answer 25

**lymecycline, methacycline, minocycline, rolitetracycline, and doxycycline**

Answer 26

Tetracyclines are broad-spectrum agents, exhibiting activity against a wide range of **gram-positive and gram-negative bacteria,** atypical organisms such as chlamydiae, mycoplasmas, and rickettsiae, and protozoan parasites. Effective against **aerobic** and **anaerobic** bacteria

Answer 27

* Women who are pregnant or breastfeeding. Tetracyclines are deposited in growing bone and teeth which can result in discolouration of teeth and occasionally dental hypoplasia.

Answer 28

* Hepatic impairment and those receiving potentially hepatotoxic drugs. * Myasthenia gravis — tetracyclines may increase muscle weakness in people with myasthenia gravis. * Systemic lupus erythematosus (SLE) — tetracyclines may exacerbate SLE symptoms. * Renal impairment — avoid excessive doses.

Answer 29

**Common or very common** Angioedema; diarrhoea; headache; Henoch-Schönlein purpura; hypersensitivity; nausea; pericarditis; photosensitivity reaction; skin reactions; systemic lupus erythematosus exacerbated; vomiting * Tooth decolouration * Headache and visual disturbances may indicate benign intracranial hypertension (discontinue treatment if raised intracranial pressure develops). NICE: * **Blood disorders** — haemolytic anaemia, thrombocytopenia, neutropenia, eosinophilia, porphyria. * **Gastrointestinal** — usually mild symptoms, but may include nausea, vomiting, dyspepsia, abdominal discomfort, diarrhoea, tooth discolouration and dental hypoplasia in children. * **Rarely:** dysphagia, oesophagitis, oesophageal irritation, For more information, see the CKS topic on [Diarrhoea - antibiotic associated](https://cks.nice.org.uk/topics/diarrhoea-antibiotic-associated/). * **Hepatic disorders** – hepatitis, jaundice, hepatic failure (rare). * **Renal disorders** — blood urea increased. * **Skin** — photosensitivity, rash, toxic epidermal necrolysis, Stevens-Johnson syndrome, angioedema, erythema multiforme, exfoliative dermatitis, drug reaction with eosinophilia and systemic symptoms (DRESS). * **Other rare adverse effects include:** * Anaphylaxis. * Arthralgia, myalgia. * Flushing. * Severe headache and/or visual disturbances — may be an early symptom of benign intracranial hypertension. * Tinnitus. * Porphyria.

Answer 30

Tetracycline antibiotics are protein synthesis inhibitors. They **inhibit the initiation of translation in variety of ways by binding to the 30S ribosomal subunit**, which is made up of 16S rRNA and 21 proteins. They inhibit the binding of aminoacyl-tRNA to the mRNA translation complex.44

Answer 31

* **Antacids (containing aluminium, calcium, or magnesium) and other medications containing iron, zinc, or bismuth —** these may reduce the absorption of doxycycline if taken concurrently. * **Barbiturates, carbamazepine, phenytoin, primidone** — these may reduce the exposure to doxycycline. Monitor and adjust the dose if necessary. * **Methotrexate** — doxycycline increases the risk of methotrexate toxicity. * **Oral hormonal contraception** — additional contraceptive precautions are not required during or after courses of doxycycline. * However, women should be advised about the importance of correct contraceptive practice if they experience vomiting or diarrhoea. For further information, see the sections on vomiting or diarrhoea in the CKS topics on [Contraception - combined hormonal methods](https://cks.nice.org.uk/topics/contraception-combined-hormonal-methods/) and [Contraception - progestogen-only methods](https://cks.nice.org.uk/topics/contraception-progestogen-only-methods/). * **Retinoids** — there is a possible increased risk of benign intracranial pressure if tetracyclines are used concurrently with retinoids (such as isotretinoin). * Avoid the concurrent use of tetracyclines and retinoids. * **Rifampicin** — rifampicin decreases exposure to doxycycline. Monitor the effects and increase doxycycline dose if necessary. * **Warfarin** — the concurrent use of warfarin with doxycycline may increase the anticoagulant effect. * Monitor the person's international normalized ratio (INR) and adjust the warfarin dose accordingly.

Answer 32

Patients should be advised to avoid exposure to sunlight or sun lamps.

Answer 33

* Penicillins * Cephalosporins * Sulphonamides (part of co-trimoxazole) Patients with a history of atopic allergy (e.g. asthma, hay fever, eczema) are more likely to be allergic to penicillins. If allergic to 1 penicillin you are allergic to all. If allergic to penicillin, may be allergic to cephalosporins. Common hypersensitivty reaction in elderly patients e.g. skin reactions when using sulphonamides

Answer 34

Many drugs are renally excreted and may also affect renal function themselves. **_Renal Function_** * Aminoglycosides e.g. gentamycin * Tetracycline * Nitrofurantoin * Amoxicillin * Vancomycin Gentamycin and Vancomycin need to have TDM. These drugs both rely on renal function to calculate intial dose.

Answer 35

**_Liver Failure_** * Choramphenicol * Co-amoxiclav * Co-trimoxazole * Tetracyclines Choramphenicol is metabolised by liver enzymes therefore hepatic monitoring is required. Co-amoxiclav = amoxicillian and clavulanic acid. Clavulanic acid component means hepatic monitoring required Co-trimoxazole - the sulphonamide component is metbolised by hepatic enzymes so hepatic monitoring required Tetracyclines - caution in liver impairment. High doses of intravenous tetracycline can induce fatty liver disease and may result in severe hepatic dysfunction, acute liver failure and death

Answer 36

* Concomitant disease states e.g. Crohn’s, UC * Vomiting & diarrhoea * Dysphagia

Answer 37

1. Pregnancy * Aminoglycosides e.g. gentamycine (toxic to feotus) * Tetracycilnes (prevent skeletal development therefore not used in children) * Quinolones e.g. ciprofloxacin (Contraindicated in children. Special cases may use in child) * Trimethoprim (terotogenic in trimester 1) * Nitrofurantion (terotogenic in trimester 3) 2. Breast feeding: * Rule of thumb - safe in pregn = safe in breast feeding * Avoid ciprofloxacin and tetracyclines 3. Oral contraception

Answer 38

**_Dehydration/inadequate fluid intake_** * Can lead to crystalluria - crystals in urine * Specifically with ciprofloxacin Sulphonamides * Counsel on importance of fluid intake

Answer 39

**_Glucose 6-phosphate dehydrogenase (G6PD) deficiency_** * Haemolytic anaemia can develop in those defieceny of enzyme. Without this enzyme some drugs are impossoble to metabolise * caution with sulphonamides, ciprofloxacin and nitrofurantoin * Susceptibility to the haemolytic risks from drugs varies * Risk & severity of haemolysis is almost dose-related * Need to avoid certain foods - check chap 9 anaemia bnf

Answer 40

Parental borad spectrum penicillins have high Na+ content

Answer 41

A Some drugs lower epileptic threshold

Answer 42

* Nausea * Particularly with erythromycin, doxocycline and nitrofurantion * Diarrohea * Oral/anogenital thrush/ pruritis (rash) * especially with sulphonamides and penicillins * Caused by broad spec see below * Broad spectrum AB can cause fungal infections. AB associated collitis, other problems associated with suprainfections e.g. vagitis and pruritis * This is due to AB killing goof and bad bacteria leading to overgrowht of other bacteria

Answer 43

* Vaginitis - metronidazole * Candidosis - topical or oral anti-fungal Antibiotic associated colitis likely to be due to a C.difficile infection - oral metronidazole, oral vancomycin, Fidaxomicin (Dificlir™) [Latter for management of recurrent C.difficile infection] Vancomycin not absorbed from GI tract therefore useful Fidaxomicin licenced for reccurent C.diff infections

Answer 44

**Penicillins Allergy** * (5-10%)urticarial rash(5%) * Joint pain,malaise,local oedema,anaphylaxis **Cephalosporins** * up to 6.5% patients cross-allergic with penicillins **Trimethoprim** * bone marrow depression in folate deficient patients, potentially teratogenic **Aminoglycosides & vancomycin** * ototoxicity, nephrotoxicity **Sulphonamides** * Stevens-Johnson syndrome & hypersensitivity, blood dyscrasias due to bone marrow depression and agranulocytosis **Doxycycline** * Photosensitivity

Answer 45

avoid sunbathing or sun beds

Answer 46

Want high level of drug in tissue where infection is * CSF - chloramphenicol, cefotaxime (meningitis) * Bones - flucloxacillin, fusidic acid * Prostate - Trimethoprim, ciprofloxacin * Urinary exretion - all excreted bar chloramphenicol

Answer 47

* Food - Decreases plasma levels of many antibacterials * Exception – Nitrofurantoin * Combined OC’s (decreased effect) - with rifampicin * Progesterone-only OC’s (decreased effect) – rifampicin * Alcohol - with Metronidazole leads to disulfuram reaction - nausea & vomiting * Antacids/iron/zinc - decrease effect of tetracyclines, doxycycline & ciprofloxacin * Warfarin * Antiepileptics * Rifampicin decreases efficitivty * Theophylline

Answer 48

Penicillins, erythromycin and Cephalosporins (cefalexin (1st gen cefalexin, 2nd gen ceftriaxone, 1st gen cefadroxil)- all but Cefopime a 4th generation cephalosporin

Answer 49

Metronidazole is an antimicrobial drug with high activity against **anaerobic** **bacteria and protozoa.** It is effective against both gram **positive** and **negative** bacteria.

Answer 50

Metronidazole itself is ineffective. It is a stable compound able to penetrate into microorganisms. Under anaerobic conditions nitroso radicals acting on DNA are formed from metronidazole by the microbial pyruvate-ferredoxin-oxidoreductase, with oxidation of ferredoxin and flavodoxin. Nitroso radicals form adducts with base pairs of the DNA, thus leading to breaking of the DNA chain and consecutively to cell death.

Answer 51

Metronidazole is indicated in the prophylaxis and treatment of infections in which anaerobic bacteria have been identified or are suspected to be the cause (see sections 4.4 and 5.1). Metronidazole is indicated in adults and children for the following indications: 1) Prevention of post-operative infections due to anaerobic bacteria (gynecological and intra-abdominal operations) 2) Urogenital trichomoniasis in the female and in man. 3) Bacterial vaginosis (also known as non-specific vaginitis) 4) The treatment of septicaemia, bacteraemia, peritonitis, brain abscess, necrotising pneumonia, osteomyelitis, puerperal sepsis, pelvic abscess, pelvic cellulitis and post- operative wound infections from which pathogenic anaerobes have been isolated. 5) All forms of amoebiasis (intestinal and extra-intestinal disease and asymptomatic cyst passers). 6) Acute ulcerative gingivitis. 7) Giardiasis. 8) Acute dental infections (e.g. acute pericoronitis and acute apical infections) 9) Anaerobically-infected leg ulcers and pressure sores 10) Treatment of Helicobacter pylori infection associated with peptic ulcer as part of triple therapy Consideration should be given to official guidance on the appropriate use of antibacterial agents.

Answer 52

NICE: * **Adverse effects of metronidazole include** gastrointestinal disturbances (including nausea and vomiting), taste disturbances, furred tongue, oral mucositis, and anorexia. * **Very rarely, the following may occur:** hepatitis, jaundice, pancreatitis, drowsiness, dizziness, headache, convulsion, ataxia, psychotic disorders (including confusion and hallucinations), darkening of urine, thrombocytopenia, pancytopenia, myalgia, arthralgia, visual disturbances, rash, pruritus, and erythema multiforme. * Advise the person not to drive or operate machinery if drowsiness, dizziness, confusion, hallucinations, convulsions, or transient visual disturbances occur. * Severe bullous skin reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) or acute generalised exanthematous pustulosis (AGEP) have been reported. If symptoms/signs are present, treatment must be immediately discontinued. BNF: Common/very common: **With topical use** Skin reactions **With vaginal use** Pelvic discomfort; vulvovaginal candidiasis; vulvovaginal disorders

Answer 53

**With topical use** Avoid exposure to strong sunlight or UV light **With vaginal use** Avoid intravaginal preparations (particularly those that require the use of an applicator) in young girls who are not sexually active, unless there is no alternative (in children); not recommended during menstruation; some systemic absorption may occur with vaginal gel * Active or chronic severe peripheral and central nervous system disease (due to the risk of neurological aggravation). * Severe liver disease and hepatic encephalopathy (due to substantial impairment of metronidazole clearance) — reduce the total daily [dose](https://cks.nice.org.uk/topics/lacerations/prescribing-information/metronidazole/#licensed-doses) to one-third, and give once daily.

Answer 54

None - bnf NICE: * Known metronidazole or nitroimidazole hypersensitivity. * Cockayne syndrome. Cases of severe hepatotoxicity/acute hepatic failure, including cases with a fatal outcome with very rapid onset after treatment initiation in patients with Cockayne syndrome have been reported

Answer 55

not licensed for use in children under 18 years

Answer 56

* **Alcohol** — some people taking oral metronidazole experience a disulfiram-like reaction (flushing, increased respiratory rate, increased pulse rate, nausea, headache, and dizziness) with alcohol. * Although there is no conclusive evidence to support this interaction, warn the person that they *might* experience this reaction if they drink alcohol whilst taking metronidazole. Alcohol should be avoided during treatment with metronidazole and for at least 48 hours afterwards. * **Anticoagulants** — the anticoagulant effects of warfarin can be markedly increased by metronidazole. * Monitor the international normalized ratio (INR) if metronidazole is given with warfarin, and adjust the warfarin dose accordingly. * Warn the person of the possible risk of increased bruising and bleeding, and advise them on when to seek medical help. * **Ciclosporin** — people receiving ciclosporin are at risk of elevated serum ciclosporin levels. * When co-administration of metronidazole and ciclosporin is necessary, monitor serum ciclosporin and creatinine levels closely. * **Lithium** — raised lithium levels accompanied by evidence of possible renal damage has been reported in people treated concurrently with lithium and metronidazole. * Before starting metronidazole in a person taking lithium, seek specialist advice regarding tapering or stopping lithium treatment. If concurrent treatment is unavoidable, plasma concentrations of lithium, creatinine, and electrolytes should be monitored closely. * Lithium treatment should be tapered or withdrawn before administering metronidazole. * Plasma concentrations of lithium, creatinine and electrolytes should be monitored in patients under treatment with lithium while they receive metronidazole.

Answer 57

Patients should be advised not to take alcohol during metronidazole therapy and for at least 48 hours afterwards because of the possibility of a disulfiram-like (antabuse effect) reaction.

Answer 58

Patients should be advised not to take alcohol during metronidazole therapy and for at least 48 hours afterwards because of the possibility of a disulfiram-like (antabuse effect) reaction.

Answer 59

Clindamycin is active against **Gram-positive cocci**, including streptococci and penicillin-resistant staphylococci, **and also against many anaerobes**, especially *Bacteroides fragilis*.

Answer 60

It is well concentrated in bone and excreted in bile and urine.

Answer 61

* **Acne vulgaris** * **Bacterial vaginosis** * **Treatment of falciparum malaria (to be given with or following quinine)** * **Cellulitis,Erysipelas** * **Diabetic foot** **Staphylococcal bone and joint infections,Chronic sinusitis,Lower respiratory-tract infections,Complicated intra-abdominal infections,Pelvic and female genital infections,Skin and soft-tissue infections** **Staphylococcal bone and joint infections such as osteomyelitis,Peritonitis,Intra-abdominal sepsis,Meticillin-resistant** ***Staphylococcus aureus*** **(MRSA) in bronchiectasis, bone and joint infections, and skin and soft-tissue infections** **Treatment of mild to moderate pneumocystis pneumonia (in combination with primaquine)**

Answer 62

* Sensitive to Clindamycin, lincomycin, or to any excipients * should not be used in patients with **existing diarrhoea**

Answer 63

Clindamycin binds to the 50S subunit of the bacterial ribosome and inhibits the early stages of protein synthesis. The action of clindamycin is predominately bacteriostatic, though high concentrations may be slowly bactericidal against sensitive strains.

Answer 64

**General side-effects:** **Common or very common** Skin reactions **Specific side-effects:** **Common or very commonWith oral use** Abdominal pain; antibiotic associated colitis; diarrhoea (discontinue) **Uncommon** **With oral use** Nausea; vomiting **Frequency not known** **With oral use** Agranulocytosis; angioedema; eosinophilia; gastrointestinal disorders; jaundice; leucopenia; neutropenia; severe cutaneous adverse reactions (SCARs); taste altered; thrombocytopenia; vulvovaginal infection **With parenteral use** Abdominal pain; agranulocytosis; antibiotic associated colitis; cardiac arrest; diarrhoea (discontinue); eosinophilia; hypotension; jaundice; leucopenia; nausea; neutropenia; severe cutaneous adverse reactions (SCARs); taste altered; thrombocytopenia; thrombophlebitis; vomiting; vulvovaginal infection **With topical use** Abdominal pain; antibiotic associated colitis; folliculitis gram-negative; gastrointestinal disorder **With vaginal use** Constipation; diarrhoea (discontinue); dizziness; gastrointestinal discomfort; headache; increased risk of infection; nausea; vertigo; vomiting; vulvovaginal irritation **Side-effects, further information** **Antibiotic-associated colitis:** * Clindamycin has been associated with antibiotic-associated colitis, which may be fatal. Although antibiotic-associated colitis can occur with most antibacterials, it occurs more frequently with clindamycin. If *C. difficile* infection is suspected or confirmed, discontinue the antibiotic if appropriate. Seek specialist advice if the antibiotic cannot be stopped and the diarrhoea is severe. **Systemic side-effects (with vaginal use):** * Clindamycin 2% cream is poorly absorbed into the blood—low risk of systemic effects.

Answer 65

**With systemic use** * Avoid in [Acute porphyrias](https://bnf.nice.org.uk/treatment-summaries/acute-porphyrias/) **CautionsFor Dalacin® 2% cream** * Avoid intravaginal preparations (particularly those that require the use of an applicator) in young girls who are not sexually active, unless there is no alternative (in children)

Answer 66

**Muscle relaxants:** Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, it should be used with caution in patients receiving such agents. **Antibacterial agents:** Antagonism has been demonstrated between clindamycin and erythromycin *in vitro*. Due to possible clinical significance, the two drugs should not be administered concurrently and therefore clindamycin should not be given in combination with macrolides or streptogramin antibacterial agents. **Neostigmine and pyridostigmine:** Clindamycin antagonises the effects of the above anticholinesterases. **Vaccines:** Oral typhoid vaccine is inactivated by concomitant administration of antibacterial. Thus, clindamycin should be avoided for 3 days before and after oral typhoid vaccination**.** **Vitamin K antagonists:** Increased coagulation tests (PT/INR) and/or bleeding, have been reported in patients treated with clindamycin in combination with a vitamin K antagonist (e.g. warfarin, acenocoumarol and fluindione). Coagulation tests, therefore, should be frequently monitored in patients treated with vitamin K antagonists

Answer 67

Damages latex condoms and diaphragms.

Answer 68

**With systemic use** Monitor liver and renal function if treatment exceeds 10 days. **With systemic use in children** Monitor liver and renal function in neonates and infants.

Answer 69

Patients and their carers should be advised to discontinue and contact a doctor immediately if severe, prolonged or bloody diarrhoea develops. **With oral use:** Capsules should be swallowed with a glass of water.