Fluoroquinolones

Classification and Chemistry

Classification

Fluoroquinolones are a class of broad-spectrum antibiotics. The common medications in the class include:

• 1st generation: norfloxacin (no longer clinically used)
• 2nd generation:
  • Ciprofloxacin (prototypical drug)
  • Ofloxacin
• 3rd generation:
  • Levofloxacin
  • Moxifloxacin
  • Gemifloxacin
• 4th generation: delafloxacin

Chemical structure

Fluoroquinolone structures:

• Bicyclic core structure (all)
• Ketone functional group (quinolones)
• Fluorine atom (fluoroquinolones)

Mechanisms of Action and Resistance

Mechanism of action

• Fluoroquinolones directly inhibit bacterial DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure synthesis Synthesis Polymerase Chain Reaction (PCR) by binding to:
  • Topoisomerase II ( DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure gyrase) in gram-negative organisms
  • Topoisomerase IV in gram-positive Gram-Positive Penicillins organisms
• Topoisomerase enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes:
  • Unwind DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure prior to replication
  • Have both nuclease ( DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure cleaving) and ligase ( DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure repairing) activity
• Fluoroquinolone binding to enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes results in:
  • Inhibition of ligase activity only
  • DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure cleavage without the ability to repair the DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure
  • Cessation of DNA replication DNA replication The entire DNA of a cell is replicated during the S (synthesis) phase of the cell cycle. The principle of replication is based on complementary nucleotide base pairing: adenine forms hydrogen bonds with thymine (or uracil in RNA) and guanine forms hydrogen bonds with cytosine. DNA Replication with broken DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure strands
  • Cell death Cell death Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects. Cell Injury and Death → fluoroquinolones are bactericidal Bactericidal Penicillins

Mechanisms of resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing

The dominant mechanisms of fluoroquinolone resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing:

• ↓ Accumulation of the drug within bacterial cells:
  • ↓ Expression of porin channels Channels The Cell: Cell Membrane → ↓ entry of the drug into cells
  • ↑ Expression of efflux pumps Efflux Pumps Lincosamides
• ↓ Affinity of the drug to the target:
  • Chromosomal point mutations change the structure of the topoisomerase and affect the binding site.
  • The mutations are drug and bug specific (e.g., gyrA genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure in Neisseria gonorrhoeae Neisseria gonorrhoeae A species of gram-negative, aerobic bacteria primarily found in purulent venereal discharges. It is the causative agent of gonorrhea. Neisseria)
  • Plasmid-mediated resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing (typically a low-level resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing)

Clinically important resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing patterns

As resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing to fluoroquinolones becomes more common, fluoroquinolone use may be limited for the following indications:

• Neisseria gonorrhoeae Neisseria gonorrhoeae A species of gram-negative, aerobic bacteria primarily found in purulent venereal discharges. It is the causative agent of gonorrhea. Neisseria
• Pseudomonas aeruginosa Pseudomonas aeruginosa A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. Aeruginosa is a major agent of nosocomial infection. Pseudomonas
• Urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract: Anatomy infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease (UTIs)
• Typhoid Typhoid Typhoid (or enteric) fever is a severe, systemic bacterial infection classically caused by the facultative intracellular and Gram-negative bacilli Salmonella enterica serotype Typhi (S. Typhimurium, formerly S. typhi). S. paratyphi serotypes A, B, or C can cause a similar syndrome. Enteric Fever (Typhoid Fever)

Pharmacokinetics

Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption

• Well absorbed in the upper GI tract
• Good oral bioavailability Bioavailability Pharmacokinetics and Pharmacodynamics:
  • Levofloxacin (99%) > moxifloxacin (90%) > gemifloxacin/ciprofloxacin (70%) > delafloxacin (60%)
  • Ingestion with dairy, mineral supplements, and most antacids can significantly ↓ bioavailability Bioavailability Pharmacokinetics and Pharmacodynamics
• Peak concentrations: 1–3 hours after an oral dose

Distribution

• Large volumes of distribution (VD): most exceed the total body water Total body water Body Fluid Compartments volume → the drug accumulates in the tissue
• Drugs concentrate in:
  • Prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. tissue
  • Bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy and stool
  • Lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy
  • Kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy (except moxifloxacin)
  • Neutrophils Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation and macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation

Metabolism

• < 15% of drug concentrations undergo hepatic metabolism (except moxifloxacin)
• Moxifloxacin:
  • Approximately 50% of the drug is metabolized in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy.
  • Metabolized via glucuronidation and sulfate conjugation Conjugation A parasexual process in bacteria; algae; fungi; and ciliate eukaryota for achieving exchange of chromosome material during fusion of two cells. In bacteria, this is a unidirectional transfer of genetic material; in protozoa it is a bi-directional exchange. In algae and fungi, it is a form of sexual reproduction, with the union of male and female gametes. Bacteriology rather than CYP450 mechanisms
• Ciprofloxacin: 
  • Inhibits CYP1A2 → can ↑ the levels of drugs metabolized by CYP1A2
  • Some affected drugs include:
    • Clozapine Clozapine A tricyclic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2a/2c receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. Second-Generation Antipsychotics
    • Theophylline Theophylline A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3. Asthma Drugs
    • Tizanidine Tizanidine Spasmolytics

Excretion

• Elimination Elimination The initial damage and destruction of tumor cells by innate and adaptive immunity. Completion of the phase means no cancer growth. Cancer Immunotherapy:
  • Primarily via renal tubular secretion Secretion Coagulation Studies (except moxifloxacin)
  • Some fecal excretion for ciprofloxacin, moxifloxacin, gemifloxacin, and delafloxacin
• Moxifloxacin:
  • Hepatic clearance
  • May be used in renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome
  • Should not be used for UTIs
• Half-life Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Pharmacokinetics and Pharmacodynamics: 3–9 hours (typically dosed twice daily)

Spectrum of Activity

Fluoroquinolones are considered broad-spectrum antibiotics: Ciprofloxacin covers gram-negative rods the best; Levofloxacin and moxifloxacin provide excellent coverage of most potential respiratory pathogens; Delafloxacin covers both P. aeruginosa P. aeruginosa A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. Aeruginosa is a major agent of nosocomial infection. Pseudomonas and MRSA MRSA A strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins. Staphylococcus.

Aerobic gram-negative organisms

• Drugs with activity:
  • Most fluoroquinolones are highly active against gram-negative rods.
  • Ciprofloxacin has the most activity.
• Organisms covered by fluoroquinolones:
  • Enterobacteriaceae Enterobacteriaceae A family of gram-negative, facultatively anaerobic, rod-shaped bacteria that do not form endospores. Its organisms are distributed worldwide with some being saprophytes and others being plant and animal parasites. Many species are of considerable economic importance due to their pathogenic effects on agriculture and livestock. Cephalosporins: 
    • Escherichia coli Escherichia coli The gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. Escherichia coli
    • Klebsiella Klebsiella Klebsiella are encapsulated gram-negative, lactose-fermenting bacilli. They form pink colonies on MacConkey agar due to lactose fermentation. The main virulence factor is a polysaccharide capsule. Klebsiella pneumoniae is the most important pathogenic species. Klebsiella spp.
    • Proteus Proteus Proteus spp. are gram-negative, facultatively anaerobic bacilli. Different types of infection result from Proteus, but the urinary tract is the most common site. The majority of cases are caused by Proteus mirabilis (P. mirabilis). The bacteria are part of the normal intestinal flora and are also found in the environment. Proteus spp.
  • Haemophilus Haemophilus Haemophilus is a genus of Gram-negative coccobacilli, all of whose strains require at least 1 of 2 factors for growth (factor V [NAD] and factor X [heme]); therefore, it is most often isolated on chocolate agar, which can supply both factors. The pathogenic species are H. influenzae and H. ducreyi. Haemophilus spp.
  • Moraxella catarrhalis Moraxella catarrhalis Gram-negative aerobic cocci of low virulence that colonize the nasopharynx and occasionally cause meningitis; bacteremia; empyema; pericarditis; and pneumonia. Moraxella
  • P. aeruginosa (ciprofloxacin > levofloxacin and delafloxacin > moxifloxacin)
  • Neisseria meningitidis Neisseria meningitidis A species of gram-negative, aerobic bacteria. It is a commensal and pathogen only of humans, and can be carried asymptomatically in the nasopharynx. When found in cerebrospinal fluid it is the causative agent of cerebrospinal meningitis. It is also found in venereal discharges and blood. There are at least 13 serogroups based on antigenic differences in the capsular polysaccharides; the ones causing most meningitis infections being a, b, c, y, and w-135. Each serogroup can be further classified by serotype, serosubtype, and immunotype. Neisseria and N. gonorrhoeae N. gonorrhoeae A species of gram-negative, aerobic bacteria primarily found in purulent venereal discharges. It is the causative agent of gonorrhea. Neisseria

Aerobic gram-positive Gram-Positive Penicillins organisms

• Drugs with activity: 
  • Primarily the later generation drugs: 
    • Levofloxacin
    • Moxifloxacin
    • Delafloxacin
  • Ciprofloxacin has limited-to-no activity against gram-positive Gram-Positive Penicillins organisms.
• Organisms covered:
  • Staphylococcus aureus Staphylococcus aureus Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications. Brain Abscess ( MRSA MRSA A strain of Staphylococcus aureus that is non-susceptible to the action of methicillin. The mechanism of resistance usually involves modification of normal or the presence of acquired penicillin binding proteins. Staphylococcus by delafloxacin only)
  • Some Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus spp. (including S. pneumoniae)

Atypical and anaerobic respiratory pathogens

Atypical organisms 

• Drugs with activity:
  • Levofloxacin
  • Moxifloxacin
• Organisms covered: 
  • Mycobacterium Mycobacterium Mycobacterium is a genus of the family Mycobacteriaceae in the phylum Actinobacteria. Mycobacteria comprise more than 150 species of facultative intracellular bacilli that are mostly obligate aerobes. Mycobacteria are responsible for multiple human infections including serious diseases, such as tuberculosis (M. tuberculosis), leprosy (M. leprae), and M. avium complex infections. Mycobacterium spp. (M. tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis):
    • 2nd-line agents to treat tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis
    • Used in cases of resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing and/or intolerance to 1st-line agents
  • Legionella Legionella Legionella is a facultative intracellular, gram-negative bacilli. Legionella does not grow on common culture media because it requires certain supplementation (cysteine and iron). Legionella pneumophila (L. pneumophila) accounts for the majority of human infections. Legionella/Legionellosis spp.
  • Chlamydia pneumoniae Chlamydia pneumoniae A species of chlamydophila that causes acute respiratory infection, especially atypical pneumonia, in humans, horses, and koalas. Chlamydia

Anaerobic organisms

• Moxifloxacin only
• Covers anaerobic respiratory infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:
  • Aspiration pneumonia Aspiration pneumonia A type of lung inflammation resulting from the aspiration of food, liquid, or gastric contents into the upper respiratory tract. Pneumonia
  • Lung abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease
• Generally not effective against Bacteroides Bacteroides Bacteroides is a genus of opportunistic, anaerobic, gram-negative bacilli. Bacteroides fragilis is the most common species involved in human disease and is part of the normal flora of the large intestine. Bacteroides (limited use for intra-abdominal infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease)

Other organisms

Fluoroquinolones are also considered 1st-line options against susceptible infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease caused by:

• Bacillus anthracis Bacillus anthracis A species of bacteria that causes anthrax in humans and animals. Anthrax
• Francisella tularensis Francisella Tularensis Aminoglycosides
• Salmonella typhi Salmonella typhi A serotype of Salmonella enterica which is the etiologic agent of typhoid fever. Enteric Fever (Typhoid Fever)
• Yersinia pestis Yersinia pestis The plague is a bacterial infection caused by Yersinia pestis (Y. pestis), which primarily infects rodents. The disease is transmitted to humans via a flea bite. Inhalation of infectious droplets and handling infected animals or laboratory specimens are other means of transmission. The plague has 3 forms: bubonic (most common form), septicemic, and pneumonic. Yersinia pestis/Plague

Indications

Compared to other antibiotics, fluoroquinolones are associated with a higher risk of potentially permanent and disabling adverse events. Therefore, fluoroquinolones are generally not used for uncomplicated infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease and should only be used against susceptible bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology.

Complicated infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease

• Genitourinary infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:
  • Complicated UTIs and pyelonephritis Pyelonephritis Pyelonephritis is infection affecting the renal pelvis and the renal parenchyma. This condition arises mostly as a complication of bladder infection that ascends to the upper urinary tract. Pyelonephritis can be acute or chronic (which results from persistent or chronic infections). Typical acute symptoms are flank pain, fever, and nausea with vomiting. T Pyelonephritis and Perinephric Abscess
  • Prostatitis Prostatitis Prostatitis is inflammation or an irritative condition of the prostate that presents as different syndromes: acute bacterial, chronic bacterial, chronic prostatitis/chronic pelvic pain, and asymptomatic. Bacterial prostatitis is easier to identify clinically and the management (antibiotics) is better established. Prostatitis (acute and chronic)
  • Pelvic inflammatory disease Pelvic inflammatory disease Pelvic inflammatory disease (PID) is defined as a polymicrobial infection of the upper female reproductive system. The disease can affect the uterus, fallopian tubes, ovaries, and adjacent structures. Pelvic inflammatory disease is closely linked with sexually transmitted diseases, most commonly caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and Gardnerella vaginalis. Pelvic Inflammatory Disease
  • May be used in uncomplicated cystitis Cystitis Inflammation of the urinary bladder, either from bacterial or non-bacterial causes. Cystitis is usually associated with painful urination (dysuria), increased frequency, urgency, and suprapubic pain. Urinary tract infections (UTIs) when no alternative options exist
• Respiratory infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:
  • Hospital-acquired pneumonia Hospital-Acquired Pneumonia Pneumonia in Children
  • Pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia caused by multidrug-resistant (MDR) S. pneumoniae
  • Atypical pneumonia Atypical pneumonia Mycoplasma
  • Tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis (levofloxacin and moxifloxacin (2nd-line agents))
  • May be used in uncomplicated infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease when no alternative options exist:
    • Bacterial sinusitis Sinusitis Sinusitis refers to inflammation of the mucosal lining of the paranasal sinuses. The condition usually occurs concurrently with inflammation of the nasal mucosa (rhinitis), a condition known as rhinosinusitis. Acute sinusitis is due to an upper respiratory infection caused by a viral, bacterial, or fungal agent. Sinusitis
    • Chronic obstructive pulmonary disease Pulmonary disease Diseases involving the respiratory system. Blastomyces/Blastomycosis ( COPD COPD Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD)) exacerbations
• Abdominal infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:
  • Complicated intra-abdominal infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease (in combination with metronidazole Metronidazole A nitroimidazole used to treat amebiasis; vaginitis; trichomonas infections; giardiasis; anaerobic bacteria; and treponemal infections. Pyogenic Liver Abscess for anaerobic coverage)
  • Peritonitis Peritonitis Inflammation of the peritoneum lining the abdominal cavity as the result of infectious, autoimmune, or chemical processes. Primary peritonitis is due to infection of the peritoneal cavity via hematogenous or lymphatic spread and without intra-abdominal source. Secondary peritonitis arises from the abdominal cavity itself through rupture or abscess of intra-abdominal organs. Penetrating Abdominal Injury and infection related to a peritoneal dialysis Peritoneal dialysis Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. Peritoneal Dialysis and Hemodialysis catheter
• Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions, soft tissue Soft Tissue Soft Tissue Abscess, and musculoskeletal infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:
  • Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types and joint infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease (including prosthetic joint infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease)
  • Diabetic foot Foot The foot is the terminal portion of the lower limb, whose primary function is to bear weight and facilitate locomotion. The foot comprises 26 bones, including the tarsal bones, metatarsal bones, and phalanges. The bones of the foot form longitudinal and transverse arches and are supported by various muscles, ligaments, and tendons. Foot: Anatomy infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
  • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
  • Surgical prophylaxis Prophylaxis Cephalosporins in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship allergic to 1st-line agents (e.g., cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with “cef-” or “ceph-.” Cephalosporins)
  • Infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease from bite wounds
• Nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease: bacterial meningitis Bacterial meningitis Bacterial infections of the leptomeninges and subarachnoid space, frequently involving the cerebral cortex, cranial nerves, cerebral blood vessels, spinal cord, and nerve roots. Meningitis

Infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease caused by single organisms

• Travelers diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea (E. coli, Shigella Shigella Shigella is a genus of gram-negative, non-lactose-fermenting facultative intracellular bacilli. Infection spreads most commonly via person-to-person contact or through contaminated food and water. Humans are the only known reservoir. Shigella, or Campylobacter Campylobacter Campylobacter (“curved bacteria”) is a genus of thermophilic, S-shaped, gram-negative bacilli. There are many species of Campylobacter, with C. jejuni and C. coli most commonly implicated in human disease. Campylobacter)
• Typhoid Typhoid Typhoid (or enteric) fever is a severe, systemic bacterial infection classically caused by the facultative intracellular and Gram-negative bacilli Salmonella enterica serotype Typhi (S. Typhimurium, formerly S. typhi). S. paratyphi serotypes A, B, or C can cause a similar syndrome. Enteric Fever (Typhoid Fever) fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever ( Salmonella typhi Salmonella typhi A serotype of Salmonella enterica which is the etiologic agent of typhoid fever. Enteric Fever (Typhoid Fever))
• Anthrax Anthrax Anthrax is an infection caused by the bacterium Bacillus anthracis, which usually targets the skin, lungs, or intestines. Anthrax is a zoonotic disease and is usually transmitted to humans from animals or through animal products. Symptoms depend on which organ system is affected. Anthrax ( Bacillus anthracis Bacillus anthracis A species of bacteria that causes anthrax in humans and animals. Anthrax)
• Tularemia ( Francisella tularensis Francisella Tularensis Aminoglycosides)
• Plague Plague The plague is a bacterial infection caused by Yersinia pestis (Y. pestis), which primarily infects rodents. The disease is transmitted to humans via a flea bite. Inhalation of infectious droplets and handling infected animals or laboratory specimens are other means of transmission. The plague has 3 forms: bubonic (most common form), septicemic, and pneumonic. Yersinia pestis/Plague ( Yersinia pestis Yersinia pestis The plague is a bacterial infection caused by Yersinia pestis (Y. pestis), which primarily infects rodents. The disease is transmitted to humans via a flea bite. Inhalation of infectious droplets and handling infected animals or laboratory specimens are other means of transmission. The plague has 3 forms: bubonic (most common form), septicemic, and pneumonic. Yersinia pestis/Plague)
• Cat scratch disease ( Bartonella henselae Bartonella henselae A species of gram-negative bacteria that is the etiologic agent of bacillary angiomatosis. This organism can also be a cause of cat-scratch disease in immunocompetent patients. Bartonella)
• Cholera Cholera An acute diarrheal disease endemic in india and southeast Asia whose causative agent is Vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. Vibrio ( Vibrio cholerae Vibrio cholerae The etiologic agent of cholera. Vibrio)
• Chancroid Chancroid Chancroid is a highly transmissible STD caused by Haemophilus ducreyi. The disease presents with painful ulcer(s) on the genital tract (termed chancroid or “soft chancre”). Up to 50% of patients will develop painful inguinal lymphadenopathy. Chancroid ( Haemophilus ducreyi Haemophilus ducreyi A species of Haemophilus that appears to be the pathogen or causative agent of the sexually transmitted disease, chancroid. Haemophilus)

Adverse Effects and Contraindications

Adverse effects

Fluoroquinolones carry higher risks than many other antibiotics, which limits the use. Although adverse effects are uncommon, some may be permanent or severe.

• Neurologic effects:
  • Common mild effects: 
    • Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
    • Dizziness Dizziness An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. Lateral Medullary Syndrome (Wallenberg Syndrome)
    • Insomnia Insomnia Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. Insomnia (transient)
  • Less common, more serious effects:
    • Peripheral neuropathy Neuropathy Leprosy (may be permanent)
    • Delirium Delirium Delirium is a medical condition characterized by acute disturbances in attention and awareness. Symptoms may fluctuate during the course of a day and involve memory deficits and disorientation. Delirium, psychosis, and/or hallucinations Hallucinations Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders. Schizophrenia
    • Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
  • Exacerbation of myasthenia gravis Myasthenia Gravis Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Myasthenia Gravis
• Musculoskeletal effects (especially in growing children and teenagers):
  • Tendinopathy, including tendon rupture:
    • Most often the Achilles tendon
    • Advise individuals to stop taking fluoroquinolone if pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and/or swelling Swelling Inflammation develop.
  • Arthropathy Arthropathy Osteoarthritis:
    • Cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology erosions Erosions Corneal Abrasions, Erosion, and Ulcers
    • Noninflammatory effusions
• GI effects:
  • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, and/or abdominal discomfort
  • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea (less common)
  • Clostridioides difficile infection
  • Hepatotoxicity Hepatotoxicity Acetaminophen (several drugs have been removed from the market due to hepatotoxicity Hepatotoxicity Acetaminophen)
• Cardiovascular effects:
  • QT prolongation
  • Aortic aneurysm Aortic aneurysm An abnormal balloon- or sac-like dilatation in the wall of aorta. Thoracic Aortic Aneurysms and dissection
• Other effects:
  • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions rashes Rashes Rashes are a group of diseases that cause abnormal coloration and texture to the skin. The etiologies are numerous but can include irritation, allergens, infections, or inflammatory conditions. Rashes that present in only 1 area of the body are called localized rashes. Generalized rashes occur diffusely throughout the body. Generalized and Localized Rashes
  • Phototoxicity
  • Dysglycemia (highest risk is with moxifloxacin in diabetic individuals)

Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation

• Hypersensitivity to fluoroquinolones
• Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
• Growing children and teenagers
• Concurrent use with other medications prolonging the QT interval QT interval Electrocardiogram (ECG)
• Myasthenia gravis Myasthenia Gravis Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Myasthenia Gravis
• Use with caution with:
  • Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
  • Rheumatoid arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis (risk of tendon rupture)
  • Aortic aneurysm Aortic aneurysm An abnormal balloon- or sac-like dilatation in the wall of aorta. Thoracic Aortic Aneurysms/dissection
  • Renal impairment (ciprofloxacin, levofloxacin, and delafloxacin)
  • Hepatic impairment (moxifloxacin)

Comparison of Medications

Comparison based on mechanisms of action

Antibiotics can be classified in several ways. One way is to classify antibiotics by mechanism of action:

Comparison based on coverage

Different antibiotics have varying degrees of activity against different bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology. The table below outlines the antibiotics with activity against 3 important classes of bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: gram-positive Gram-Positive Penicillins cocci Cocci Bacteriology, gram-negative bacilli Bacilli Shigella, and anaerobes Anaerobes Lincosamides.