infections.pdf

Chapter Six : Infections 6.1-Antibacterials 6.1.1-Aminoglycosides 1-These include amikacin, gentamicin, neomycin, streptomycin, and tobramycin (1). 2-All are bactericidal and active against some Gram-positive and many Gram- negative organisms. Tobramycin has similar activi...

Chapter Six : Infections 6.1-Antibacterials 6.1.1-Aminoglycosides 1-These include amikacin, gentamicin, neomycin, streptomycin, and tobramycin (1). 2-All are bactericidal and active against some Gram-positive and many Gram- negative organisms. Tobramycin has similar activity to gentamicin. It is slightly more active against Ps. aeruginosa (1). 3-Amikacin is more stable than gentamicin to enzyme inactivation. Amikacin is used in the treatment of serious infections caused by gentamicin-resistant Gram- negative bacilli (1). 4-The aminoglycosides are not absorbed from the gut and must therefore be given by injection for systemic infections (1). Neomycin sulfate may be given orally to reduce the bacterial population of the colon prior to bowel surgery or in hepatic failure (1). 5-Once daily administration of aminoglycosides is more convenient than multiple daily dose regimens (1). 6-Tobramycin can be administered by nebuliser or by inhalation of powder on a cyclical basis (28 days of tobramycin followed by a 28-day tobramycin-free interval) for the treatment of chronic pulmonary Ps. aeruginosa infection in cystic fibrosis (1). 7-The important side-effects are ototoxicity, and nephrotoxicity (1). 8-Streptomycin is used mainly for tuberculosis (2nd line drug) and for brucellosis and endocarditis (1). 9-Monitoring requirements (1).  Serum concentration monitoring.  Renal function should be assessed before starting an aminoglycoside and during treatment.  Auditory and vestibular function should also be monitored during treatment. Aminoglycosides Scientific name Trade names Dosage form 1 2 3 4 89  Any extra notes: 6.1.2-Carbapenems 1-These include imipenem (with cilastatin), ertapenem and meropenem (1). 2-The carbapenems are beta-lactam antibacterials with a broad-spectrum of activity which includes many Gram-positive and Gram-negative bacteria, and anaerobes. Unlike the other carbapenems, ertapenem is not active against Pseudomonas (1). 3-Imipenem is partially inactivated by enzymatic activity and is therefore administered in combination with cilastatin, a specific enzyme inhibitor (1). 4-Meropenem has less seizure-inducing potential and can be used to treat central nervous system infection (1). 5-Some products contain combination of carbapenems with vaborbactam or relebactam (beta-lactamase inhibitors) (1). Carbapenems Scientific name Trade names Dosage form 1 2 Any extra notes: 6.1.3-Cephalosporins Cephalosporins are antibacterials that cause bacterial cell lysis and death (1). 1-Classification (Table 6-1) (1, 2) Table 6-1: Cephalosporins (1, 2) Groups Examples 1 First-generation Cefalexin and cefadroxil 2 Second -generation Cefuroxime 3 Third-generation Cefotaxime, ceftazidime ceftriaxone, cefixime, cefpodoxime 4 Fourth-generation Cefepime 5 Fifth generation [Anti- methicillin Ceftaroline resistant Staphylococcus aureus (MRSA) cephalosporin) 91 2-They have more broad-spectrum antimicrobial activity than penicillins, activity that broadens in spectrum when moving from first- to fourth-generation agents (2). In general the activity against gram negative bacteria is increase and the activity against gram positive bacteria is decrease when we move from first to third generations cephalosporins (3). 3-Some important properties for specific agents (Table 6-2): Table 6-2: Properties for specific cephalosporins Drug Properties Ceftriaxone Has a longer half-life (may be given once daily) (1). Ceftazidime Has good activity against pseudomonas (1). Cefixime Oral third-generation cephalosporin (1). Cefpodoxime Oral third-generation cephalosporin (administer tablets with food; suspension may be administered without regard to food) (4). 4-The principal side-effect of the cephalosporins is hypersensitivity and about 0.5–6.5% of penicillin-sensitive patients will also be allergic to the cephalosporins. Patients with a history of immediate hypersensitivity to penicillin should not receive a cephalosporin (contraindicated) (1). 5-Note: Arrhythmias following rapid injection are reported (1). 6-Important: A-Ceftriaxone is incompatible with Ca-containing solutions, e.g. Hartmann‘s, Ringer‘s. Fatalities have occurred in neonates and infants due to precipitates forming in lungs and kidneys (5). B-Ceftriaxone should not to be given simultaneously with infusion fluids containing Ca, even by different infusion lines. May be infused sequentially (1) (EXCEPT in neonate (4)) with infusion fluids containing Ca if flush with NaCl 0.9% between infusions or give infusions by different infusion lines at different sites (1). 7-Some products contain combination of cephalosporins with tazobactam or avibactam (beta-lactamase inhibitors) (1). Cephalosporins Scientific name Trade names Dosage form 1 2 3 4 91  5 6 Any extra notes: 6.1.4-Glycopeptide antibiotic 1-The glycopeptides teicoplanin, telavancin and vancomycin have bactericidal activity against aerobic and anaerobic Gram-positive bacteria including multi- resistant staphylococci (1). 2-Dalbavancin is a glycopeptide antibacterial; it has bactericidal activity against Gram-positive bacteria including various staphylococci (1). 3-Teicoplanin is similar to vancomycin, but has a significantly longer duration of action, allowing once daily administration and is associated with a lower incidence of nephrotoxicity than vancomycin (1). 4-Injection of (teicoplanin and vancomycin) can be used to prepare solution for oral administration (for Clostridium difficile infection) (1). 5-Vancomycin is typically administered by slow IV infusion. More rapid infusion rates can cause the red man syndrome (rash, flushing, tachycardia, hypotension) If red man syndrome occurs, it may be ameliorated by slowing the rate of infusion (2). Glycopeptide Scientific name Trade names Dosage form 1 2 Any extra notes: 6.1.5-Lincosamides (lincomycin and clindamycin) 1-Active against Gram-positive cocci, and also against many anaerobes (1). The main indication for the use of lincosamides is now in the treatment of severe anaerobic infections (3). 2-Clindamycin is much better absorbed from the GIT than lincomycin. They both penetrate well into bone and have been used successfully in osteomyelitis (3). 3-The capsules of clindamycin should be taken with a glass of water (3). 92 4-They have also been used topically in the treatment of acne vulgaris (3). 5-Important: Patients and their carers should be advised to discontinue and contact a doctor immediately if severe, prolonged or bloody diarrhea develops. (1) (Lincosamides are reported to produce diarrhea. In some patients severe antibiotic-associated or pseudomembranous colitis may develop during therapy or up to several weeks afterwards) (3). Lincosamides Scientific name Trade names Dosage form 1 2 Any extra notes: 6.1.6-Macrolides 1-These include erythromycin, azithromycin and clarithromycin (1). 2-This class of antibiotics has activity against gram-positive cocci, including streptococci and staphylococci, and some upper respiratory gram-negative bacteria, but minimal activity against enteric gram-negative rods (6). 3-Azithromycin has a long half-life and once daily dosage is recommended (1). 4-Important : Azithromycin capsules must be given on an empty stomach (an hour before food or 2 hours after food) while azithromycin tablet and suspension are given without regard to meal (1). 5-Clarithromycin is usually given twice daily. And it is one of the component of triple therapy for eradication of H. pylori (a bacteria that cause ulcer) (1). 6-Spiramycin is also a macrolide which is used for the treatment of toxoplasmosis (1). Macrolides Scientific name Trade names Dosage form 1 2 3 Any extra notes: 93 6.1.7-Monobactam Aztreonam is monobactam antibiotic with an antibacterial spectrum limited to Gram-negative aerobic bacteria including Pseudomonas aeruginosa, Neisseria meningitidis, and Haemophilus influenzae (1). Scientific name Trade names Dosage form Any extra notes: 6.1.8-Metronidazole and tinidazole 1-They are active against anaerobic bacteria and protozoa (Entamoeba histolytica, giardia lamblia). Tinidazole is similar to metronidazole but has a longer duration of action (1, 3). 2-Metronidazole and tinidazole tablets are taken with or after food (1). 3-Tinidazole may be given at a dose of 2 g (4 tablets) for some vaginal and GIT infections (3). 4-They can produce nausea and an unpleasant metallic taste (3). 5-When given with alcohol, metronidazole and tinidazole may provoke a disulfiram-like reaction in some patients (3). Scientific name Trade names Dosage form 1 2 Any extra notes: 6.1.9-Penicillins The penicillins are bactericidal and act by interfering with bacterial cell wall synthesis (1). 1-Classification of penicillins (Table 6-3) (1). 94  Table 6-3: Classification of penicillins Penicillin groups Examples 1 Natural penicillins Benzylpenicillin and phenoxymethylpenicillin 2 Penicillinase-resistant Flucloxacillin, Temocillin penicillins 3 Broad-spectrum Amoxixillin, ampicillin penicillins 4 Antipseudomonal Piperacillin (combined with the beta-lactamase penicillins inhibitor tazobactam), Ticarcillin (combined with the beta-lactamase inhibitor clavulanic acid) 2-Ampicillin and amoxicillin are active against certain gram-positive and gram- negative organisms but are inactivated by penicillinases (1). 3-Both piperacillin and ticarcillin have a broad spectrum of activity against a range of Gram-positive and Gram-negative bacteria, and anaerobes. High doses may lead to hypernatremia (owing to sodium content of preparations) (1). 4-Co-amoxiclav consists of amoxicillin with the beta-lactamase inhibitor clavulanic acid. Clavulanic acid inactivates beta-lactamases, making the combination active against beta-lactamase-producing bacteria that are resistant to amoxicillin (1). 5-Various combinations between amoxicillin and clavulanic acid are presents (Table 6-4): Table 6-4: Amoxicillin-Clavulanic acid combinations Combinations Dosage form Notes 156 ( 125 +31) suspension 312 ( 250 + 62) suspension 457( 400 + 57) suspension Given twice daily(every 12 hours) 375 ( 250 + 125) Tablet 625( 500 + 125) Tablet 1000 ( 875 +125) Tablet Given twice daily(every 12 hours) 600 (500 + 100) Injection For intravenous injection only 1200 (1000 + 200) Injection For intravenous injection only 6-The most important side-effect of the penicillins is hypersensitivity which causes rashes and anaphylaxis and can be fatal (1). 7-Ampicillin, and flucloxacillin must be given on an empty stomach (this means an hour before food or 2 hours after food) while amoxicillin may be taken without regard to meal (1). 8-For the eradication of H. pylori (a bacteria that cause ulcer), amoxicillin is given in combination with other drugs; usual doses of amoxicillin for the eradication of H. pylori is 1 g twice daily (1). 95 9-Benzathine penicillin G is indicated for prophylaxis of rheumatic fever. It is given by deep intramuscular injection every 3–4 weeks. (1). Penicillins Scientific name Trade names Dosage form 1 2 3 4 5 Any extra notes: 6.1.10-Quinolones 1-These include Nalidixic acid, Delafloxacin, Ciprofloxacin, Gatifloxacin, Ofloxacin, Levofloxacin, Moxifloxacin (1, 3). 2-Nalidixic acid: Because bactericidal concentrations can only be achieved in urine its use has generally been limited to the treatment of urinary-tract infections. (3). 3-Ciprofloxacin is active against both Gram-positive and Gram-negative bacteria. It is particularly active against Gram-negative bacteria. Ciprofloxacin can be used for infections like respiratory tract infections (but not for pneumococcal pneumonia), urinary-tract infections, and infections of the gastro-intestinal system (including typhoid fever) (1). 4-Respiratory fluoroquinolones: Levofloxacin, moxifloxacin, and gemifloxacin have improved coverage of streptococci but generally less gram-negative activity than ciprofloxacin (except levofloxacin, which does cover P. aeruginosa) (6). 5-Quinolones cause arthropathy in the weight-bearing joints of immature animals and are therefore generally not recommended in children and growing adolescents. However, the significance of this effect in humans is uncertain and in some specific circumstances short-term use of ciprofloxacin may be justified in children (7). 6-Nalidixic acid should be avoided in infants less than 3 months old (3). 7-Administration: Ciprofloxacin should not be taken with dairy products (interfere with the absorption) (1). 96 8-Driving and skilled tasks: Quinolones may impair performance of skilled tasks (e.g. driving) (1). 9-Quinolones cause acute haemolytic anaemia when taken by individuals with Glucose 6-phosphate dehydrogenase (G6PD) deficiency (1). 10-Concomitant administration with aluminum- or magnesium-containing antacids, oral iron, oral calcium, and oral zinc preparations can markedly impair absorption of all orally administered fluoroquinolones (6). Quinolones Scientific name Trade names Dosage form 1 2 3 4 5 Any extra notes: 6.1.11-Sulfonamides and trimethoprim 1-Sulfamethoxazole and trimethoprim are used in combination (as co- trimoxazole) because of their synergistic activity (1). Trimethoprim is also used alone particularly in the treatment of infections of the urinary and respiratory tracts (3). 2-It is commonly used for treating sinusitis, otitis media, bronchitis, prostatitis, and UTIs (6). 3-Co-trimoxazole should not generally be given to infants below 6 weeks of age because of the risk of kernicterus. Co-trimoxazole should be avoided by people with G6PD deficiency (3). 4-All patients should be asked whether they are allergic to "sulfa drugs" (6). 5-Co-trimoxazole is the preferred drug for both the treatment and prophylaxis of pneumocystis pneumonia (3). Scientific name Trade names Dosage form 1 97 Any extra notes: 6.1.12-Tetracyclines (like Tetracycline, and Doxycycline) 1-Tetracyclines all have a broad spectrum of activity which includes Gram-positive and Gram-negative bacteria, chlamydias, rickettsias, mycoplasmas, spirochaetes, and some mycobacteria, and some protozoa (3). 2-Doxycycline has longer duration than tetracycline and may be given once or twice daily (1). 3-Important : Oral administration: A-Tetracycline must be given on an empty stomach (this means an hour before food or 2 hours after food) (1). B-Capsules (of tetracycline, and doxycycline) should be swallowed whole with plenty of fluid while sitting or standing (1) (because it may cause oesophageal irritation). 4-Gastrointestinal disturbances are common and other important toxic effects include deposition in bones and teeth, precluding their use in pregnancy (2), breast- feeding (1) and young children; and photosensitivity, especially with demeclocycline (3). 5-They may cause photosensitivity: Patients should be advised to avoid exposure to sunlight or sun lamps (1). 6-Di- and trivalent cations: Greatly decrease absorption of tetracyclines (2). Tetracyclines Scientific name Trade names Dosage form 1 2 Any extra notes: 6.1.13-Antituberculosis drugs 1-First-line agents form the core of initial regimens for the treatment of TB. Currently, isoniazid, rifampicin (rifampin), pyrazinamide, and ethambutol are considered first-line agents. In specific situations, rifabutin and rifapentine may be considered first-line agents (8). 98 2-Treatment of active TB : The standard treatment of active tuberculosis is completed in two phases—an initial phase using four drugs (isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months) and a continuation phase using two drugs (isoniazid and rifampin for 4 months) (1, 9). 3-Multidrug resistant tuberculosis (MDR-TB), caused by strains resistant to both isoniazid and rifampicin, requires a combination of first- and second -line drugs for at least 1 8 to 24 months (3). 4-The second -line drugs are generally less effective and more toxic than standard therapy and need be taken daily. They include injectable drugs such as aminoglycosides (amikacin and kanamycin), polypeptide capreomycin, as well as further oral drugs such as the fluoroquinolones (levofloxacin, moxifloxacin, and ofloxacin) (3). 5-Isoniazid is the preferred drug for treating latent TB infection. Generally, isoniazid alone is given for 9 months. Rifampin for 4 months can be used when isoniazid resistance is suspected or when the patient cannot tolerate isoniazid (9). 6-INH antagonizes vitamin B6 metabolism and potentially can cause a peripheral neuropathy. This can be avoided or minimized by coadministration of pyridoxine, 25-50 mg PO daily, especially in the elderly, in pregnant women, and in patients with diabetes, renal failure, alcoholism, and seizure disorders (6). 7-Rifampicin in combination with doxycycline is also used for brucellosis. It also used for prevention of secondary case of meningococcal meningitis (used for 2 days) (1). 8-Isoniazid must be taken 30 to 60 minutes before food. Rifampicin is Taken on an empty stomach (an hour before food or 2 hours after food) (1). 9-Important : Rifampicin causes a harmless orange-red discoloration of the urine, faeces, sweat, saliva, sputum, tears, and other body fluids (3). 10-Ethambutol ocular toxicity (color blindness, loss of visual acuity, optic neuritis) : The patients should be advised to discontinue therapy immediately if they develop deterioration in vision and promptly seek further advice (1). Antituberculosis drugs Scientific name Trade names Dosage form 1 2 3 4 5 99 Any extra notes: 6.1.14-Other antibacterials (Table 6-5): Table 6-5: Other antibacterials Antibacterials comments 1-It is a potent broad spectrum antibiotic (1). 2-Associated with serious hematological side-effects 1 Chloramphenicol (aplastic anaemia) when given systemically and should therefore be reserved for the treatment of life-hreatening infections (1). Used for dermatitis herpetiformis, leprosy and 2 Dapsone Pneumocystis jirovecii (1). Daptomycin is a lipopeptide antibacterial with a spectrum of activity similar to vancomycin but its efficacy against enterococci has not been established. It 3 Daptomycin needs to be given with other antibacterials for mixed infections involving Gram-negative bacteria and some anaerobes (1). Fidaxomicin is a macrocyclic antibacterial that is poorly 4 Fidaxomicin absorbed from the gastro-intestinal tract, and, therefore, it should not be used to treat systemic infections (1). 1-It is active against a range of Gram-positive and Gram-negative (1). 2-A single 3 gm dose is used for acute uncomplicated 5 Fosfomycin lower urinary-tract infections. It is also used for other indications (Osteomyelitis, hospital-acquired lower respiratory-tract infections, and Bacterial meningitis) (1). Narrow spectrum antibiotics used for staphylococcal 6 Fusidic acid infections (1). Active against Gram-positive bacteria including 7 Linezolid methicillin resistant Staphylococcus aureus (MRSA) (1). 1-Nitrofurantoin is used in the treatment and prophylaxis of urinary-tract infections (UTI) (3). 2-It is given orally, with food or milk (3). 3-Important: Prophylactic dose of antibiotic for UTI 8 Nitrofurantoin usually given at bedtime (10). 4-Nitrofurantoin may cause a brownish discoloration of the urine (3). 111  1-Poorly absorbed from the gastro-intestinal tract, and, therefore, should not be used to treat systemic infections (1) 9. Rifaximin 2-Used for reduction in recurrence of hepatic encephalopathy. It also used for Travellers‘ diarrhea (1). Used for the treatment of acute bacterial skin and skin 10 Tedizolid structure infections (1). Tigecycline is a glycylcycline antibacterial structurally related to the tetracyclines. Tigecycline is active against Gram-positive and Gram-negative bacteria, 11 Tigecycline including tetracycline-resistant organisms, and some anaerobes. It is also active against meticillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci (1). 6.2-Antifungal drugs (systemic use) 1-Examples of systemic antifungal drugs are listed in (Table 6-6) (1). Table 6-6: Systemic antifungal drugs (1). Class Examples 1 Echinocandin Anidulafungin, Caspofungin, Micafungin, antifungals 2 Polyene antifungals Amphotericin B, Nystatin. 3 Triazole antifungals Fluconazole, Isavuconazole, Itraconazole, Posaconazole, Voriconazole 4 Others Flucytosine, Griseofulvin 2-Fluconazole 150 mg as a single oral dose may be used for vaginal candidiasis and Candidal balanitis. While for recurrent vulvovaginal candidiasis: Initially 150 mg every 72 hours for 3 doses, then 150 mg once weekly for 6 months (1). 3-Lipid formulations of amphotericin are significantly less toxic and are recommended when the conventional formulation of amphotericin is contra- indicated because of toxicity, especially nephrotoxicity or when response to conventional amphotericin is inadequate (1). 4-Echinocandin antifungals are only active against Aspergillus spp. and Candida spp (1). 5-Itraconazole can be administered as intermittent ‗pulse’ therapy (1). 6-Concerning griseofulvin (important) : A-Effective contraception required during and for at least 1 month after administration to women. Also men should avoid fathering a child during and for at least 6 months after administration (1). B-Absorption of griseofulvin from the GIT is enhanced by reducing the particle size or when given with a fatty meal (should be given with or after meals) (2). 111  C-Duration of therapy is dependent on the site of the infection and may extend to a number of months (1) (2 to 8 weeks for infections of the hair and skin, up to 6 months for infections of the fingernails, and 12 months or more for infections of the toenails) (3). D-It may impair performance of skilled tasks (e.g. driving) (1). E-Griseofulvin use has been superseded by newer antifungals, particularly for nail infections (1). 7-Nystatin is used for oral, oropharyngeal, and perioral infections by local application in the mouth (1). And it may be given orally for the treatment of intestinal candidiasis (3). 8-Itraconazole capsule must be given after food. While Oral solution is taken on an empty stomach (an hour before food or 2 hours after food) (1). 9-Posaconazole oral suspension should be taken with food (preferably a high fat meal) or nutritional supplement to ensure adequate exposure for systemic effects. Where possible, tablets should be used in preference to suspension because tablets have a higher bioavailability (1). 10-Voriconazole tablet and suspension are taken on an empty stomach (an hour before food or 2 hours after food) (1). 11-Bone marrow depression can occur with flucytosine which limits its use (1). Systemic antifungal drugs Scientific name Trade names Dosage form 1 2 3 4 5 Any extra notes: 6.3-Anthelmintics 1-The most common anthelmintics drugs available in Iraq are mebendazole and albendazole. 2-Other anthelmintics are ivermectin, levamisole, and praziquantel (1). 112 3-For the treatment of pinworms (Enterobius vermicularis): A-Mebendazole is the drug of choice for treating threadworm infection in patients of all ages over 6 months. It is given as a single dose of 100 mg; as reinfection is very common, a second dose may be given after 2 weeks (1). B-Albendazole may also be given as a single dose of 400 mg; as reinfection is very common, a second dose may be given after 2 weeks (3, 10). 4-Hydatid disease A-Surgical treatment remains the method of choice in many situations. Albendazole is used in conjunction with surgery to reduce the risk of recurrence or as primary treatment in inoperable cases (1). B-Alveolar echinococcosis is usually fatal if untreated. Surgical removal with albendazole cover is the treatment of choice, but where effective surgery is impossible, repeated cycles (1) (28-day course is repeated after 14 days without treatment) (3) of albendazole (for a year or more) may help. Careful monitoring of liver function is particularly important during drug treatment (1). 5-Mebendazole is effective against Ascaris lumbricoides and is generally considered to be the drug of choice; the usual dose is 100 mg twice daily for 3 days (1). Anthelmintics Scientific name Trade names Dosage form 1 2 Any extra notes: 6.4-Antiprotozoal drugs 6.4.1-Amoebicides 1-Amoebicides [Metronidazole, Tinidazole (discussed previously)] and Diloxanide furoate. 2-Metronidazole is the drug of choice for acute invasive amoebic dysentery. Tinidazole is also effective. Treatment with metronidazole (or tinidazole) is followed by a 10-day course of diloxanide furoate (1). 3-Diloxanide furoate is the drug of choice for asymptomatic patients with E. histolytica cysts in the faeces; metronidazole and tinidazole are relatively ineffective. The usual course is of 10 days (1). 4-For amoebic abscesses of the liver metronidazole is effective; tinidazole is an alternative (1). 113 5-Flatulence is the most common adverse effect during treatment with diloxanide furoate (3). Scientific name Trade names Dosage form 1 Any extra notes: 6.4.2-Drugs for toxoplasmosis (Spiramycin) 1-Seropositive females infected 6 months before conception have no risk of fetal transmission. (11). If toxoplasmosis is acquired in pregnancy, transplacental infection may lead to severe disease in the fetus (1). 2-Spiramycin may reduce the risk of transmission of maternal infection to the fetus (1). Spiramycin (3 g daily in divided doses) should be given until term (11). Note: 1 g = 3,000,000 units. Scientific name Trade names Dosage form Any extra notes: 6.4.3-Leishmaniacides Sodium stibogluconate (pentostam®), is used (I.M or I.V) for visceral leishmaniasis (kala-azar). Some early non-inflamed lesions of cutaneous leishmaniasis can be treated with intralesional injections of sodium stibogluconate (1). Scientific name Trade names Dosage form Any extra notes: 6.4.4-Antimalarials Drugs used for treatment or prophylaxis of malaria are listed in (Table 6-7) (12). 114  Table 6-7: Antimalarials (12). Drugs used for treatment of malaria Drugs used for malaria prophylaxis 1-Artesunate 1-Atovaquone/proguanil 2-Artemether with lumefantrine 2-Chloroquine phosphate 3-Atovaquone/proguanil 3-Doxycycline 4-Chloroquine Phosphate 4-Hydroxychloroquine 5-Clindamycin 6-Doxycycline 5-Mefloquine 7-Hydroxychloroquine 6-Primaquine phosphate 8-Mefloquine 9-Primaquine 7-Sulfadoxine/pyrimethamine phosphate 10-Quinidine gluconate 11-Quinine sulfate 12-Tetracycline 6.5-Antiviral drugs 6.5.1- Hepatitis 1-The most common types of viral hepatitis include hepatitis: A (HAV), B (HBV), C (HCV), D (HDV), and E (HEV) (13). 2-Most persons with acute hepatitis (especially hepatitis A, B, and E) recover spontaneously and do not require specific antiviral therapy (14). 3-Chronic Hepatitis B Treatment A-The immune-mediating agents approved for HBV treatment are interferon (IFN)-alfa and pegylated (peg) IFN-alfa. The nucleos(t)ide antiviral agents lamivudine, telbivudine, adefovir, entecavir, and tenofovir diprovoxil and tenofovir alafenamide are approved treatment options for chronic HBV (9). B-Although pegIFN has lack of resistance, its disadvantages include the need for subcutaneous injections and a pronounced adverse-effect profile that may require dosage reductions or treatment discontinuation (13). C-Entecavir and tenofovir are potent antivirals with a high barrier to genetic resistance, and so are the most appropriate first-line agent (11). D-Adefovir, lamivudine, and telbivudine are not recommended due to high rates of resistance (13). 4-Chronic Hepatitis C Treatment A-Treatment is recommended for all HCV-infected persons (9). B-Before starting treatment, the genotype of the infecting hepatitis C virus should be determined as this may affect the choice and duration of treatment (9). C-IFN and pegIFN are no longer recommended for chronic HCV (13). Direct-acting antiviral agents: [simeprevir, paritaprevir (boosted with ritonavir), ledipasvir, ombitasvir, sofosbuvir, dasabuvir, daclatasvir, velpatasvir, grazoprevir, elbasvir, voxilaprevir] (1) have higher cure rates (well above 90%), fewer adverse effects, and shorter treatment durations (13) 115  D-Recommended regimens for chronic hepatitis C are shown in (Tables 6-8 and 6-9) (15). Table 6-8. Recommendations for simplified, genotyping/subtyping-free treatment of HCV- monoinfected or HCV-HIV coinfected adult (>−18 years) and adolescent (12–17 years) patients with chronic hepatitis C without cirrhosis or with compensated (Child-Pugh A) cirrhosis, including treatment-naïve patients (defined as patients who have never been treated for their HCV infection) and treatment-experienced patients (defined as patients who were previously treated with pegylated IFN-α and ribavirin; pegylated IFN-α, (15) ribavirin and sofosbuvir; or sofosbuvir and ribavirin). Table 6-9. Recommendations for genotype/subtype-based treatment of HCV-monoinfected or HCV-HIV coinfected adult (>−18 years) and adolescent (12-17 years) patients with chronic hepatitis C without cirrhosis or with compensated (Child-Pugh A) cirrhosis, including treatment-naïve patients (defined as patients who have never been treated for their HCV infection) and treatment-experienced patients (defined as patients who were previously treated with pegylated IFN-α and ribavirin; pegylated IFN-α, ribavirin and (15) sofosbuvir; or sofosbuvir and ribavirin). RASs, resistance-associated substitutions. 5-The recommended treatment for HDV is pegIFN for 48 weeks (13). Drugs for viral hepatitis Scientific name Trade names Dosage form 1 2 3 116 4 Any extra notes: 6.5.2- Herpes virus infections 1-Antivral agents for herpes virus infections are aciclovir, famciclovir, valaciclovir, foscarnet (1). 2-Foscarnet is use for simplex virus infection unresponsive to aciclovir in immunocompromised patients; men should avoid fathering a child during and for 6 months after treatment (1). 6.5.2.1-Herpes simplex infections 1-Herpes infection of the mouth and lips and in the eye is generally associated with herpes simplex virus serotype 1 (HSV-1). Genital infection is most often associated with HSV-2 and also HSV-1 (1). 2-Topical antiviral treatment is not routinely recommended in immunocompetent individuals with uncomplicated infection of the lips (herpes labialis or cold sores) or herpetic gingivostomatitis. However, some patients may find application of a topical antiviral drug helpful when used from the onset of the prodromal phase (1). 3-Oral antiviral treatment may be considered in patients with severe, frequent or persistent oral infection usually for 5 days (longer if new lesions appear during treatment or if healing incomplete) (1). 6.5.2.2-Varicella-zoster infections 1-Chickenpox is an acute disease caused by the varicella-zoster virus. Chickenpox in otherwise healthy children is usually self-limiting and complications are rare; antiviral treatment is not routinely recommended (1). 2-Chickenpox is more severe in adolescents (aged 14 years and over) and adults than in children; antiviral treatment started within 24 hours of the onset of rash may be considered, particularly for those with severe infection or at risk of complications (1). 3-Shingles (herpes zoster) is a viral infection of an individual nerve and the skin surface affected by the nerve. The infection is caused by the reactivation of the varicella-zoster virus, the same virus that causes chickenpox (1). 4-Oral antiviral treatment should be offered to patients with shingles who are immunocompromised, have non-truncal involvement (e.g. neck, limbs, perineum), or to those with moderate to severe pain or rash. Consider oral antiviral treatment for patients aged over 50 years to reduce the risk of post-herpetic neuralgia. Treatment with the antiviral should be started within 72 hours of the onset of rash (1). 117 5-Chronic pain which persists after the rash has healed (post-herpetic neuralgia) requires specific management (1). Drugs for herpes simplex infections Scientific name Trade names Dosage form 1 2 Any extra notes: 6.5.3- Cytomegalovirus infection (CMV) Drugs licensed for use in the management of CMV disease include ganciclovir (related to aciclovir), cidofovir, foscarnet sodium, letermovir, valaciclovir, and Valganciclovir (Table 6-10) (1). Table 6-10: Drugs licensed for use in the management of CMV disease (1). Antivirals Indication(s) in CMV infection 1 Cidofovir Cytomegalovirus retinitis in patients with AIDS 2 Foscarnet Treatment of cytomegalovirus disease 3 Ganciclovir Prevention and treatment of cytomegalovirus disease Prevention of CMV reactivation and disease (in recipients of 4 Letermovir an allogeneic haematopoietic stem cell transplant who are seropositive for the human CMV). 5 Valaciclovir Prevention of CMV disease following renal transplantation Initial treatment and maintenance treatment of CMV retinitis in AIDS patients. It is also licensed for preventing CMV 6 Valganciclovir disease following solid organ transplantation from a cytomegalovirus-positive donor Drugs for cytomegalovirus infection Scientific name Trade names Dosage form 1 2 Any extra notes: 6.5.4-Influenza 1-The antivirals oseltamivir and zanamivir are used for both treatment (ideally within 48 hours of symptom onset) and post-exposure prophylaxis of influenza (1). 118 2-Antiviral medications can be used to prevent influenza (1) (Table 6-11). Table 6-11: Indications and duration of use of oseltamivir and zanamivir (1). Oseltamivir (Tamiflu) Zanamivir (Relenza) Treatment Daily for 5 days Daily for 5 days Post-exposure Daily for 10 days Daily for 10 days prophylaxis of influenza Prevention of influenza Daily for up to 6 weeks Daily for up to 28 days during an epidemic 6.5.5-Respiratory syncytial virus 1-Ribavirin is licensed for administration by inhalation for the treatment of severe bronchiolitis caused by the respiratory syncytial virus (RSV) in infants, especially when they have other serious diseases. However, there is no evidence that ribavirin produces clinically relevant benefit in RSV bronchiolitis (1). 2-Palivizumab is a monoclonal antibody licensed for preventing serious lower respiratory-tract disease caused by respiratory syncytial virus in children at high risk of the disease (e.g. those with chronic lung disease, congenital heart disease) (1). Scientific name Trade names Dosage form Any extra notes: 6.5.6-HIV infection 1-Drugs used for HIV infection are listed in (Table 6-12) (1, 9). Table 6-12: drug for Drugs used for HIV infection (1, 9). Class Examples Bictegravir, Dolutegravir, Elvitegravir, 1 Integrase inhibitors (1) Raltegravir. 2 Fusion inhibitors Enfuvirtide (1). Non-nucleoside reverse Doravirine, Efavirenz, Etravirine, Nevirapine, 3 transcriptase inhibitor Rilpivirine (1). Abacavir, Emtricitabine, Lamivudine, Tenofovir Nucleoside reverse 4 alafenamide fumarate, Tenofovir disoproxil transcriptase inhibitors fumarate, Zidovudine (1). Atazanavir, Darunavir, Fosamprenavir, 5 Protease inhibitors Lopinavir, Ritonavir, Saquinavir, and Tipranavir (1). 119  chemokine receptor 5 Maraviroc (1). 6 (CCR5) antagonists Cobicistat, and low-dose ritonavir. They boost Pharmacokinetic the concentrations of other antiretrovirals 7 enhancers metabolized by CYP3A4, but have no antiretroviral activity themselves (1). 2-The regimen of choice contains a backbone of emtricitabine and either tenofovir disoproxil or tenofovir alafenamide (1). 3-An alternative backbone regimen is abacavir and lamivudine. The third drug of choice is either ritonavir-boosted atazanavir, or ritonavir-boosted darunavir, or dolutegravir, or cobicistat-boosted elvitegravir, or raltegravir, or rilpivirine. Efavirenz may be used as an alternative third drug (1). Drugs used for HIV infection Scientific name Trade names Dosage form 1 2 3 Any extra notes: References 1-BNF-81 (2021). 2-Michael AM, Jason. Frequently prescribed medications. Third edition 2019. 3-Martindale: The Complete Drug Reference, 38th Edition. Pharmaceutical Press 2014. 4-UPTODATE: 2021.Available at: https://www.uptodate.com/contents/search. 5-Alistair G., Jane W., Vincent G., Lynn B. Injectable Drugs Guide. 1st edition. Royal Pharmaceutical Society of Great Britain 2011. 6-Pavan Bhat, et al. Washington Manual of Medical Therapeutics, The, 35th Edition. Copyright 2016. 7-BNF-For children. 2019-2020. 8-David J Quan, Richard A Helms. Textbook of Therapeutics: Drug and Disease Management. 8th edition. 2006. 9-Joseph T. DiPiro, Robert L. Pharmacotherapy: A Pathophysiologic Approach, 11th Edition. 2021. 10-Zeind, Caroline S and Carvalho, Michael G. Applied Therapeutics: The clinical use of drugs, 11th ed., 2018. 11-Stuart HR, Ian DP, Mark WJ, et al, eds. Davidson‘s Principles and Practice of Medicine. 23th edition; 2018. 111