Antibiotic in Pregnancy

Introduction

Pregnant women frequently take medications. During pregnancy, the majority of women take at least one drug. There is also evidence of an increase in the usage of medications during pregnancy in the United States, from an average of 2.5 in 1976-1978 to 4.2 in 2006-2008. The opinions and risk perceptions of pregnant women influence their decisions about whether or not to use a drug during pregnancy. The availability and utilization of trustworthy information sources is thus critical to ensuring the safe and reasonable use of medications during pregnancy. The growing use of the internet and social media as a source of information and social support makes it difficult for the healthcare sector to maximize its benefits while minimizing its risks.

During pregnancy, antibiotics are frequently administered. However, the precise medication must be chosen with care. Certain antibiotics are safe to take while pregnant, while others are not. The type of antibiotic, gestation time, dose, and duration of the antibiotic all influence safety.

• Antibiotics should only be used if no other therapeutic options are available.
• When possible, avoid administering antibiotics throughout the first trimester.
• Select a drug that is risk-free (typically an older antibiotic tested on pregnant women).
• When possible, choose single prescriptions over polypharmacy.
• The smallest feasible dose has been shown to be effective.
• Advise patients not to take over-the-counter drugs while receiving antibiotics.

The common antibiotics generally considered safe during pregnancy are:

• Amoxicillin
• Clindamycin
• Penicillin
• Cefazolin
• Ampicillin
• Erythromycin
• Nitrofurantoin
• Ampicillin-Sulbactam

Other antibiotics should be avoided while pregnant. Tetracyclines, for example, such as doxycycline and minocycline, can harm a pregnant woman's liver and discolor the teeth of a developing baby.

It's also worth noting that trimethoprim and sulfamethoxazole, two antibiotics often used combined to treat urinary tract infections, have been associated to an increased risk of birth abnormalities. Although there is no direct evidence that these antibiotics cause birth abnormalities, more research is required. Meanwhile, the usage of these medications is still justified in some instances.

Amoxicillin

Amoxicillin is a semi-synthetic penicillin similar to ampicillin that was discovered in 1970. Amoxicillin is an off-white crystalline powder with a mild fragrant odor and bitter taste. It is available in anhydrous or trihydrate form. For parental preparations, sodium salt is employed. Amoxicillin is synthesized either directly or semi-synthetically from the molecule 6-aminopenicillanic acid. It is sold in conjunction with clavunate potassium.

Amoxicillin is a penicillin antibiotic that can be taken orally. The penicillin nucleus is made up of a thiazolidine ring coupled to a ß-lactam ring to which a side chain is attached. The side-chain determines the majority of the penicillin's pharmacological and antibacterial activities. The benzyl ring in the side-chain of amoxicillin expands its antibacterial effectiveness into Gram negative bacteria. Amoxicillin kills bacteria by interfering with bacterial cell wall formation. Peptidoglycan is a heteropolymeric substance that offers mechanical stability to the cell wall. The final stage of peptidoglycan synthesis involves the completion of cross-linking when the pentaglycine bridge's terminal glycine residue is linked to the pentaglycine's fourth residue. The transpeptidase enzyme that performs this step is inhibited by penicillins and cephalosporins. As a result, the bacterial cell wall weakens, cell swells and then ruptures. Amoxicillin is readily hydrolyzed by staphylococcal penicillinase.

Toxicology

• Amoxicillin has no mutagenic potential, as confirmed by extensive high-dose experimentation. Therapeutic use

Indications

• Urinary tract infections
• Otitis media
• Enteric infections
• Surgical infections
• Respiratory tract infection
• Gram negative septicemia
• Gonorrhea
• Prevention and treatment of infective endocarditis

Contraindications

• Penicillin hypersensitivity
• Glandular fever and lymphatic lymphoma
• Bacterial resistance

Adverse Reactions

• Potentially fatal side effects: Anaphylactic shock, as with other penicillins, can occur on very rare instances. Amoxicillin produces hypersensitivity reactions, including rashes and fever, can are severe or irreversible. These responses are not any more common than with other penicillins. In the event of a hypersensitive reaction, amoxicillin should be stopped.
• A modest number of cases of pseudomembranous colitis have been linked to amoxicillin. Convulsions may occur if big intravenous doses are administered. Amoxicillin has been linked to interstitial nephritis on rare occasions.
• Acute hepatic dysfunction has been linked to amoxicillin alone or in combination with clavulanic acid.
• Amoxicillin may induce a maculopapular rash in some patients, possibly as frequently as ampicillin. The pathophysiology of this rash is uncertain, but it has been linked to lymphocyte activity, which could explain why it is more common in glandular fever.
• Patients using amoxicillin may experience diarrhea throughout treatment. This effect will affect 5% or more of the population, with a higher proportion of youngsters affected. It is caused by unabsorbed antibiotics depleting sensitive bacteria from the intestinal flora. The rising resistance of Enterobacteria to ampicillin will almost certainly result in a decrease in the occurrence of amoxicillin-associated diarrhea.
• Neonates: Because of the neonatal kidney's physiological immaturity, doses of amoxicillin should be reduced.
• Breast milk: The modest amount of amoxicillin released by the mother causes few complications in the newborn. In most cases, it can thus be taken safely during lactation.
• Pregnant women: Because amoxicillin is not teratogenic, it can be used safely throughout pregnancy at the standard adult dose.
• The elderly: There are no special precautions to take when prescribing for the elderly.

Drug Interactions

• Warfarin: When amoxicillin and warfarin are taken concomitantly, INR may alter.
• Oral contraceptives: The simultaneous use of amoxicillin and an oral contraceptive might be expected to cause breakthrough bleeding or pregnancy on rare occasions, because of reduced absorption owing to diarrhea, on the basis of experience with ampicillin.

Other Significant Interactions

• Food: Food does not have the same effect on reducing the uptake of amoxicillin as it does on ampicillin. Potentially useful Interactions Probenecid: Administration of probenecid prior to dosing results in a marked increase in the mean serum concentrations of amoxicillin

Ampicillin

Ampicillin is a white crystalline powder with a mild aromatic odor and bitter taste. Ampicillin is synthesized from the penicillin nucleus via fermentation.

Pharmacology

Ampicillin is a penicillin antibiotic that is used orally. The penicillin nucleus is made up of a thiazolidine ring coupled to a ß-lactam ring to which a side chain is attached. Ampicillin kills germs by interfering with bacterial cell wall formation. Peptidoglycan is a heteropolymeric substance that offers mechanical stability to the cell wall. The final stage of peptidoglycan production involves the completion of cross-linking, and the pentaglycine bridge's terminal glycine residue is attached to the pentapeptide's fourth residue. Penicillins and cephalosporins block the transpeptidase enzyme, which accomplishes this step. As a result, the bacterial cell wall weakens, the cell expands, and finally ruptures.

Toxicology

Ampicillin, like penicillins, has no mutagenic or carcinogenic risk. Overall, it was established that using ampicillin during the first trimester of pregnancy does not raise the risk of serious congenital abnormalities.

Clinical Pharmacology

Ampicillin kills both Gram-positive and Gram-negative bacteria. The medication is ineffective against most staphylococcal infections because it is degraded by B-lactamase. Most strains of meningococcus, Haemophilus influenza, but especially those found in children, are now ampicillin resistant. Similarly, a growing proportion of Salmonella spp. is now ampicillin insensitive. Approximately 50% of E. coli isolates and the majority of Shigella and Enterobacter bacteria are currently resistant to ampicillin. Ampicillin is ineffective against Klebsiella, Pseudomonas, and Acinetobacter spp. Streptococcus viridans and Listeria monocytogenes are still susceptible to ampicillin at low concentrations. Apart from the antibacterial action, the medication has no other clinical pharmacological activity.

Pharmacokinetics

Because ampicillin is more acid stable, it is more resistant to the action of stomach acid. Food may inhibit medication absorption. Ampicillin has a half-life of 1-2 hours and a plasma protein binding rate of roughly 20%. With the exception of the liver and kidneys, ampicillin is disseminated throughout the body and is detected at lower concentrations than in serum at most places. Except during active inflammation, when a daily dose of 150 mg ampicillin per kg is administered, penetration of the blood-brain barrier is low. When given to pregnant women, it crosses the placenta, although the concentration in amniotic fluid does not reach therapeutic levels during the first trimester. A small amount of ampicillin is produced in nursing mothers' milk.

Indications

• Urinary tract infection
• Respiratory tract infection
• Otitis media 
• Enteric fever
• Meningitis
• Billiary tract infection
• Gonorrhea
• Gram negative septicemia
• Surgical infections
• Infective endocarditis

Listeriosis: Listeriosis is a serious infection usually caused by eating food contaminated with the bacterium Listeria monocytogenes.

Contraindications

• Penicillin hypersensitivity
• Ampicillin resistance

Adverse Reactions

• Potentially fatal side effects: As with all penicillins, there is a slight risk of anaphylaxis, which is more prevalent with parenteral treatment than with oral administration.
• Overdoes that are severe: Nausea, vomiting, and allergic reactions Severe or permanent side effects range from urticaria and fever to widespread anaphylaxis, but the frequency is likely to be lower than with other penicillins. The oral route can result in pseudomembranous colitis, with the usual look of the rectal mucosa, albeit at a lesser frequency than clindamycin. Convulsions may occur in other patients who have been sorted, but only at high doses of ampicillin. Although hypersensitivity myocarditis resulting in cardiac failure has been described, it is extremely rare.
• Symptomatic side effects include rashes, maculopapular look, and diarrhea.
• Other effects include: increased serum aspartate aminotransferase levels

Drug Interactions

• Warfarin (alters INR)
• Oral contraceptives: Causes breakthrough bleeding or even pregnancy

Nursing Implications

• Take this medication continuously.
• Continue with the whole course of therapy; even if the patient feels better, do not stop taking the medication.
• Take the oral medication on an empty stomach, 1 hour before or 2 hours after meals; do not take with fruit juice or soft drinks; the oral solution is stable at room temperature for 7 days and 14 days when refrigerated. It should not be used to treat other infections on its own.
• Advice about side effects: Nausea, vomiting, Gl upset (eat small, frequent meals), and diarrhea
• Report any site pain or discomfort, unusual bleeding or bruising, mouth sores, rash, hives, fever, itching, severe diarrhea, or difficulty breathing.

Ceftriaxone

Ceftriaxone is a third-generation parenteral cephalosporin with a lengthy half-life that is resistant to B-lactamases produced by Gram-negative pathogens. It is a free-flowing white/light-yellow crystalline powder. There are no combo preparations available.

Pharmacology

Ceftriaxone, like other cephalosporins and penicillins, kills germs by interfering with bacterial cell wall formation. Ceftriaxone interacts to penicillin-binding proteins in the bacterial cell wall with great affinity, interfering with peptidoglycan production. Peptidoglycan is a heteropolymeric substance that offers mechanical stability to the cell. The final stage of peptidoglycan synthesis comprises the completion of cross-linking and the pentapeptide's terminal glycine residue. Cephalosporins and penicillins block the transpeptidase enzyme, which accomplishes this step. As a result, the bacterial cell wall deteriorates, swells, and eventually ruptures. At commonly obtainable plasma concentrations, ceftriaxone is bactericidal against a wide range of microorganisms.

Toxicology

• No mutagenicity from ceftriaxone has been observed.

Clinical Pharmacology

Ceftriaxone is a third-generation cephalosporin with wide antibacterial action against both aerobic and Gram-negative pathogens. Ceftriaxone doses of 8mg/l or fewer usually kill sensitive species, although concentrations of 64mg/l can kill resistant organisms. The average elimination half-life in healthy humans is approximately 6-9 hours, which is significantly longer than that of any other cephalosporin. The medication has a high protein binding rate (95%).

Metabolism

• It is eliminated unchanged by the kidneys and liver.

Therapeutic Use

Indications

• UTI
• Lower respiratory tract infections and pneumonia
• Bacteremia/septicemia
• Gonococcal infection
• Primary syphilis and chancroid
• Skin, soft tissue, bone and joint infections
• Miscellaneous bacterial infections
• Bacterial meningitis
• Infections in cancer patients
• Prevention of postoperative infections

Contraindications

• Hypersensitivity
• Combining therapeutic with prophylactic use

Adverse Effects

Ceftriaxone has been generally well tolerated, with adverse events being rare, usually minor and temporary, and needing merely drug withdrawal.

• Pseudomonas and other forms of colitis have been linked to potentially fatal outcomes. A instance of ceftriaxone-induced acute pancreatitis has been reported. Ceftriaxone therapy has resulted in agranulocytosis.
• Only one case of acute overdose was documented when 100 times the recommended dose of ceftriaxone was given intrathecally. Jaundice and erythema multiforma have been reported as severe or irreversible side effects. Antibiotic resistance is becoming more common.
• The most common side effects are gastrointestinal - loose stool, diarrhea, sometimes nausea, vomiting, glossitis or stomatitis. Other side effects include a maculopapular rash, pruritus, urticaria, and edema.
• Other side effects: Haematological problems are uncommon, with the most prevalent being eosinophilia, thrombocytosis, leucopenia, and neutropenia. Increased liver enzyme activity was also observed.

For IV use: Ceftriaxone should be delivered intravenously by infusion over a 30-minute period. Quantities of 10 mg/ml to 40 mg/ml are advised, however lower concentrations may be utilized if necessary (may prevent venous sclerosis). In admixtures, vancomycin and fluconazole are physically incompatible with ceftriaxone. When provided concurrently with ceftriaxone by intermittent intravenous infusion, it is recommended that they be given sequentially, with complete cleansing of the intravenous lines (with one of the compatible fluids) between administrations. Saline and dextrose are compatible fluids. Never combine with TPN. Certainly not compatible with lipids. You will either require a second site or stop all other pumps, flush thoroughly, and clamp the TPN/lipid line before administration. Saline and dextrose are compatible fluids. Never combine with TPN. Certainly not compatible with lipids. You will either require a second site or stop all other pumps, flush thoroughly, and clamp the TPN/lipid line before administration. Do not use calcium-containing diluents, such as Ringer's solution or Hartmann's solution, to reconstitute or infuse Rocephin. Calcium can sometimes be found in pharmacy admixed fluids. Check the fluids again. Particulate formation is possible. Due to the possibility of incompatibility, rocephin solutions should not be physically mixed with or piggybacked into solutions containing other antimicrobial drugs or diluent solutions other than those listed above. After mixing, it does not need to be refrigerated.

Cefazolin

Cefazolin is a white to off-white powder that has a harsh flavor. It is semi-synthetically prepared. It is water and polar solvent soluble.

Pharmacology

Cefazolin is a first-generation cephalosporin that, like other cephalosporins and penicillins, kills bacteria by interfering with cell wall formation. Cefazolin binds to penicillin binding proteins in the bacterial cell wall with strong affinity. When present in insufficient amounts, these PBPs are the same as those linked to other cephalosporins. These mechanisms disrupt peptidoglycan production. Peptidoglycan is a heteropolymeric substance that offers mechanical stability to the cell wall. The final stage of peptidoglycan production involves the completion of cross-linking, and the pentaglycine bridge's terminal glycine residue is attached to the pentapeptide's fourth residue. Cephalosporins and penicillin block the transpeptidase enzyme, which accomplishes this step. As a result, the bacterial cell wall weakens, the cell expands, and finally ruptures. At commonly obtainable plasma concentrations, it is bactericidal against a wide range of microorganisms.

Toxicology

There is no proof that cefazolin is carcinogenic. There have been no reports of embryonic impacts. Cefazolin had no effect on child development or the reproductive process during organogenesis and early fetal development. Cefazolin sodium is a first-generation cephalosporin antibiotic used to treat a wide range of infections caused by susceptible organisms. Endocarditis (staphylococcal), endometritis (surgical infection prophylaxis during caesarean section), peritonitis (associated with continuous ambulatory peritoneal dialysis), and surgical infection are among them.

Indications

• Respiratory tract infection
• Skin and soft tissue infections
• Septicemia
• Surgical prophylaxis
• Genitourinary tract infections
• Bone and joint infections
• Endocarditis
• Biliary tract infections

Contraindications

Cefazolin is contraindicated in patients with known hypersensitivity to cefazolin and other ß-lactum antibiotics.

Adverse Reactions

• Cefazolin does not appear to have any potentially life-threatening side effects. Anaphylactic responses are possible and can be lethal. Pseudomembranous colitis has been reported in association with cefazolin therapy, as with other broad-spectrum antibiotics.
• There have been no reports of acute overdoses. Severe negative outcomes are unlikely. However, general supportive treatment is advised, with monitoring of renal, hematological, hepatic, and coagulation status.

Severe or irreversible adverse effects

• Hypersensitivity: Maculopapular and erythematous rashes, esonophilia, and drug fever have been reported in around 5% of people hypersensitive to penicillins. Serum nausea and anaphylaxis-like reactions have also been recorded.
• Hematological: Cefazolin use has been linked to the development of neutropenia, leucopenia, thrombocytopenia, and eosinophilia on rare occasions. A positive direct and indirect Coomb's test is detected in 1% and 0.5% of cases, respectively.
• Convulsions have been reported in patients with compromised renal function who were given big doses.

Symptomatic adverse effects

• Genital and anal pruritus, as well as genital and oral moniliasis, are among the side effects.
  Liver and renal: A transitory increase in AST, ALT, and blood urea levels has been recorded in the absence of clinical signs of hepatic or renal impairment.
  Pain, induration, and tenderness may occur in patients receiving cefazolin intramuscular injections, whereas thrombophlebitis may occur with intravenous injection.
  Other effects include: Cefazolin, like other cephalosporins, can cause isolated and transient increases in blood urea and the hepatic enzymes AST, ALT, and alkaline phosphatase.

Gentamycin

Gentamicin is an aminoglycoside antibiotic with a broad spectrum of activity against aerobic gram-negative rods. Gentamicin is also used in the treatment of infections caused by gram-positive organisms such as Staphylococcus aureus and some streptococci. Gentamicin is also used to treat endocarditis in conjunction with a penicillin antibiotic (infection of the heart). Gentamicin destroys germs (bactericidal) by blocking protein synthesis.

Mechanism of action/Effect

Aminoglycoside; actively transported across the bacterial cell membrane, binds to a particular receptor protein on the 30 S subunit of bacterial ribosomes, and inhibits protein synthesis by interfering with an initiation complex between mRNA (messenger RNA) and the 30S subunit. DNA can be misread, resulting in nonfunctional proteins; polyribosomes can be broken apart, rendering them unable to manufacture protein.

Note: Aminoglycosides are bactericidal, while most other antibiotics that interfere with protein synthesis are bacteriostatic.

Absorption

• May be absorbed in minute quantities following topical application to the eye.

Precautions to Consider

• Cross-sensitivity and/or associated issues: Patients who are sensitive to one aminoglycoside may also be sensitive to others.
• Pregnancy/Reproduction: Pregnancy studies have revealed a risk to the fetus. However, in a life-threatening situation or with a serious disease, the benefits of therapy may outweigh the risks.
• Gentamicin given to pregnant rats in daily doses roughly 500 times the maximum recommended ophthalmic human dose resulted in offspring with lower body and kidney weights.

Breast-Feeding

• Problems in humans have not been documented. Appropriate studies on the relationship of age to the effects of this medicine have not been performed in neonates. Safety and efficacy have not been established.

Contraindications

The contraindications included were chosen based on their potential clinical significance and are not necessarily exhaustive. When the following medical problem exists, the risk-benefit ratio should be considered.

Side Effects

• Edema
• Anemia, decreased white blood cell count,
• Decreased platelets, allergic reactions
• Increased salivation, visual problems
• Jearing impairment, breathing problems
• Confusion, electrolyte abnormalities
• Fever, joint pain
• Nausea, vomiting,
• Injection site reactions, hair loss
• Itching,seizures, dizziness, depression
• High or low blood pressure, kidney problems
• Headache, liver problems