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Abstract

Cephalosporins are among the most commonly used and versatile groups of ?-lactam antibiotics with broad-spectrum antimicrobial activity. Their PK and PD characteristics differ greatly between generations, which affects their clinical use and efficacy against bacterial infections. This review offers an extensive comparative study of the pharmacokinetic characteristics — such as absorption, distribution, metabolism, and excretion — and the pharmacodynamic concepts underlying the therapeutic activity of different cephalosporins. Special attention is given to how structural changes through generations affect half-life, tissue penetration, antibacterial spectrum, and resistance patterns. The review also mentions the interaction among PK/PD indices, such as time above minimum inhibitory concentration (T>MIC), and clinical endpoints. These variables are important in order to ensure optimized dosing regimens for therapeutic success with a reduced possibility of resistance. This review makes it evident that specific antibiotic therapeutic approaches based on unique PK/PD profiles would be required for improved patient treatment and fighting off the emerging epidemic of antimicrobial resistance.

Keywords

Cephalosporins, Pharmacokinetics, Pharmacodynamics, ?-lactam antibiotics, Antibacterial activity, Resistance mechanisms.

Introduction

A well-known class of β-lactam antibiotics, cephalosporins are distinguished by their structural variety and broad-spectrum action. Because of their capacity to prevent the formation of bacterial cell walls, these substances have been essential in the fight against a variety of bacterial infections since their discovery. Improvements in β-lactamase resistance, pharmacokinetic characteristics, and antibacterial spectrum have characterized the transition from first to fifth-generation cephalosporins.

It is essential to understand the pharmacokinetics (PK) and pharmacodynamics (PD) of cephalosporins in order to maximize their clinical effectiveness. Pharmacokinetics refers to the absorption, distribution, metabolism, and excretion of the drugs, which together affect their concentration at the site of infection. As an example, differences in oral bioavailability between cephalosporins require varying dosing regimens in order to obtain therapeutic concentrations. Furthermore, the mode of elimination—chiefly renal for most cephalosporins—is a factor affecting dosing in patients with impaired renal function.

Pharmacodynamics, by contrast, deals with the drug concentration-antimicrobial effect relationship. Cephalosporins have time-dependent killing, with the period that drug concentrations are sustained above the MIC being a key determinant of efficacy. This emphasizes the need for dosing regimens that provide plasma concentrations above the MIC for a sufficient duration. This review shall attempt a comparative overview of the pharmacokinetic and pharmacodynamic profiles of cephalosporins in different generations. Elucidating such parameters, this review attempts to guide clinical choice and facilitate rational use of cephalosporins in an era of increased antimicrobial resistance.

OVERVIEW:

Cephalosporins are a common class of β-lactam antibiotics produced from Acremonium (previously Cephalosporium), which were first found in the 1940s. They are structurally penicillin-related and have a β-lactam ring critical for their antimicrobial activity. Cephalosporins inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), which results in cell lysis and death. Due to their broad spectrum of activity and low toxicity, they are a mainstay in the management of both community-acquired and hospital-acquired infections.

The development of cephalosporins over the years has resulted in their being divided into five generations based on different antimicrobial spectra and pharmacological profiles. The first-generation cephalosporins, e.g., cefazolin and cephalexin, are mainly useful against gram-positive bacteria. The second-generation drugs, e.g., cefuroxime, provide increased gram-negative coverage. The third-generation cephalosporins, e.g., ceftriaxone and ceftazidime, show greater activity against gram-negative bacilli and improved penetration into CNS. Fourth-generation cephalosporins, e.g., cefepime, retain the advantages of their predecessors with higher β-lactamase stability. The most recent fifth-generation cephalosporins—including ceftaroline—are characterized by their efficacy against methicillin-resistant Staphylococcus aureus (MRSA).

Cephalosporins vary in their pharmacokinetic properties, like absorption, distribution, and elimination, and in their pharmacodynamic profiles, which determine which agent to use for a given infection. Knowledge of these differences between generations is important for efficacious therapeutic selection, particularly in a time when antimicrobial resistance remains a continuing challenge to public health. This review emphasizes comparing the agents based on pharmacokinetics and pharmacodynamics to appreciate their clinical utility and limitations.

PHARMACOKINETICS OF CEPHALOSPORINS:

Pharmacokinetics (PK) is the way in which a drug is absorbed, distributed, metabolized, and eliminated by the body. The PK profile of cephalosporins depends on their chemical structure, generation, and route of administration. These parameters are important in maximizing therapeutic effectiveness and avoiding toxicity.

  1. Absorption

Cephalosporins are given either orally or parenterally. Oral bioavailability is extremely variable: first-generation cephalosporins such as cephalexin and cefadroxil are highly bioavailable orally (~90%), whereas most third- to fifth-generation compounds (e.g., ceftriaxone, cefepime, ceftaroline) are given intravenously because of poor GI absorption or instability in gastric acid.

Food can slow gastric emptying but does not significantly decrease total absorption for oral cephalosporins such as cefuroxime axetil.

  1. Distribution

Cephalosporins are widely distributed in body fluids such as synovial, pleural, and pericardial spaces. Distribution into cerebrospinal fluid (CSF) is poor for most cephalosporins but enhances during meningeal inflammation and is best with third-generation drugs such as ceftriaxone and cefotaxime, and fourth-generation cefepime. Plasma protein binding is variable: ceftriaxone has high protein binding (~85–95%), which influences its free (active) concentration.

  1. Metabolism

All cephalosporins, except cefotaxime, are metabolized to only a small extent in the liver. Cefotaxime, however, is metabolized in part to desacetyl-cefotaxime, an active metabolite. Minimal metabolic conversion makes dosing easier and minimizes interpatient variation.

  1. Excretion

Renal excretion is the primary route for most cephalosporins. Glomerular filtration and tubular secretion are used by drugs to be excreted and reach high urine concentrations—very helpful in urinary tract infections. Ceftriaxone is, however, excreted by both renal and biliary pathways and does not need to be adjusted in mild-to-moderate renal impairment. In renal impairment patients, most cephalosporins need adjustment of dosage to avoid accumulation and toxicity.

  1. Half-life and Dosing Frequency

Half-life of elimination guides dosing interval. The first-generation agents such as cefazolin are characterized by short half-lives (~1.5–2 hours) and the need for dosing every 8 hours. This contrasts with ceftriaxone with its extended half-life (~8 hours), which is amenable to once-daily dosing in most indications. Extended half-lives promote patient compliance and optimize the use of healthcare resources, especially among outpatients.

PHARMOCODYNAMICS OF CEPHALOSPORINS:

Pharmacodynamics (PD) is the drug concentration versus antimicrobial effect against target pathogens. For cephalosporins, as with other β-lactam antibiotics, their bactericidal activity is time-dependent. This is to say their efficacy is proportional to the length of time the drug concentration is above the minimum inhibitory concentration (MIC) for the infecting pathogen during the dosing interval.

  1. Mechanism of Action

Cephalosporins block bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), enzymes required for peptidoglycan cross-linking. Blocking of PBPs results in abnormal cell wall formation, osmotic instability, and ultimate bacterial lysis and death. This action is most effective against dividing bacteria. Cephalosporins are typically bactericidal, not just bacteriostatic.

  1. Time-Dependent Killing

The pharmacodynamic parameter with highest correlation with clinical effectiveness of cephalosporins is the percentage of the dosing interval that the concentration of free drug is above the MIC (%fT > MIC). It is suggested by studies that for maximal bacterial killing, cephalosporin concentrations need to be above the MIC for more than 60–70% of the dosing interval [3,4]. More frequent dosing or continuous infusion will ensure effective drug levels, particularly in critically ill patients.

  1. Post-Antibiotic Effect (PAE)

Cephalosporins have little or no post-antibiotic effect in action against the majority of gram-negative bacteria, in that activity quickly returns after drug concentrations drop below the MIC. A mild PAE can be seen against some gram-positive bacteria, for example, Streptococcus pneumoniae. Therefore, it is important to ensure continuous or frequent exposure above the MIC to prolong bactericidal action.

  1. Spectrum of Activity

The antimicrobial activity of cephalosporins increases with each subsequent generation. First-generation cephalosporins (e.g., cefazolin) are primarily active against gram-positive cocci. Second-generation drugs (e.g., cefuroxime) have some gram-negative activity. Third-generation cephalosporins (e.g., ceftriaxone, ceftazidime) are more active against gram-negative bacteria and some have penetration into the central nervous system. Fourth-generation cephalosporins (e.g., cefepime) and fifth-generation drugs (e.g., ceftaroline) provide expanded coverage, including Pseudomonas and MRSA activity, respectively.

  1. Resistance Considerations

Pharmacodynamic efficacy can be undermined by mechanisms of bacterial resistance, e.g., β-lactamase production (including ESBLs and AmpC), modified PBPs, and decreased permeability across the bacterial membrane. Certain newer-generation cephalosporins have been engineered to circumvent such resistance mechanisms. Ceftazidime-avibactam, for instance, acts against certain carbapenem-resistant Enterobacteriaceae by pairing a cephalosporin with a β-lactamase inhibitor.

Comparative Analysis Between Generations:

Pharmacodynamic efficacy can be undermined by mechanisms of bacterial resistance, e.g., β-lactamase production (including ESBLs and AmpC), modified PBPs, and decreased permeability across the bacterial membrane. Certain newer-generation cephalosporins have been engineered to circumvent such resistance mechanisms. Ceftazidime-avibactam, for instance, acts against certain carbapenem-resistant Enterobacteriaceae by pairing a cephalosporin with a β-lactamase inhibitor.

Generation

Key

example

Spectrum of

Activity

β-Lactamase Stability

CSF Penetration

Clinical Use

 

1st

 

 

Cephalexin, Cefazolin

 

Gram-positive (Staph/Strep), limited gram-neg

low

poor

Skin infections, surgical prophylaxis

 

2nd

Cefuroxime, Cefaclor

Improved gram-neg (H. influenzae, Neisseria)

moderate

limited

RTIs, sinusitis, otitis media

 

3rd

Ceftriaxone, Ceftazidime

Improved gram-neg (H. influenzae, Neisseria)

Higher

Good

Meningitis, pneumonia, sepsis

 

4th

Cefepime

Extended gram-neg

High

Good

 

 

Febrile neutropenia, nosocomial

 

 

5th

Ceftaroline, Ceftobiprole

MRSA, VRSA, multidrug-resistant Strep

Very High

Moderate

 

MRSA-related skin infections

 

 

Clinical Applications Based on PK/PD Profiles:

Knowledge of the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of cephalosporins enables sound clinical decision-making. Time-dependent killing and the need to have drug concentrations greater than the minimum inhibitory concentration (MIC) (%fT > MIC) are at the heart of their therapeutic success. Dosage regimen, spectrum of activity, tissue penetration, and clearance by the kidneys all enter into the choice of an ideal cephalosporin for an infection.

  1. Respiratory Tract Infections
  • Frontline drugs for CAP are ceftriaxone and cefotaxime because they have excellent tissue penetration in lungs, prolonged half-life, and good coverage of Streptococcus pneumoniae and Haemophilus influenzae.
  • Use of cefuroxime is indicated where outpatient use can be facilitated with oral bioavailability and intermediate activity.

PD Rational: S. pneumoniae T > MIC on a once-a-day regimen using ceftriaxone.

  1. Urinary Tract Infections (UTIs)
  • First-generation drugs such as cefalexin are suitable for uncomplicated UTIs because of elevated urinary excretion.
  • In case of complicated or drug-resistant infection, cefepime or ceftazidime can be employed because of Pseudomonas coverage.

PK Rationalization: The majority of cephalosporins have excellent urinary concentrations because of renal excretion, which increases effectiveness against UTIs.

  1. Skin and Soft Tissue Infections
  • Cefazolin is indicated for surgical prophylaxis, and for the treatment of MSSA-related skin infection.
  • Fifth-generation cephalosporins such as ceftaroline are useful against MRSA-related cellulitis and abscess.

PD Rationale: Strong protein binding and protracted serum concentrations substantiate effectiveness in soft tissue penetration.

  1. Central Nervous System Infections
  • Cefotaxime and ceftriaxone are the favorites for bacterial meningitis as a result of efficient cerebrospinal fluid (CSF) penetration in inflammation.
  • Cefepime is also being thought of for nosocomial meningitis caused by Pseudomonas risk.

PK Rationale: Ability to penetrate across the blood–brain barrier in inflamed meninges with sustained CSF levels above MIC.

  1. Intra-abdominal and Surgical Prophylaxis
  • Cefotetan and cefoxitin (2nd generation) are utilized for anaerobic prophylaxis in colorectal procedures.
  • Cefazolin is the drug of choice as a prophylactic for clean operations.

PD Rationale: Sustained peritoneal fluid levels with preoperative dosing.

  1. Febrile Neutropenia and Sepsis
  • Cefepime is employed because of its broadened gram-negative activity, such as Pseudomonas, and excellent penetration into several tissues.

PK/PD Rationale: High plasma concentrations and extensive distribution, in combination with prolonged infusion regimens, maximize %fT > MIC.

Challenges and Future Directions:

Cephalosporins have been the pillar of antibacterial therapy as a result of their broad activity, safety margin, and pharmacologic flexibility. Yet, their long-term activity and clinical relevance are threatened by various challenges requiring strategic innovations and studies.

  1. Emerging Resistance

The greatest challenge is the rapid development of resistance, especially among gram-negative organisms. ESBLs, AmpC β-lactamases, and carbapenemase-producing bacteria (e.g., KPC, NDM) can inactivate a majority of cephalosporins, leaving limited treatment options for serious infections like ventilator-associated pneumonia, bloodstream infections, and complicated urinary tract infections. Resistance not only decreases efficacy but also necessitates combination therapy, usually with β-lactamase inhibitors or non-β-lactam agents.

For instance, ceftazidime-avibactam and cefiderocol have been designed to surmount particular β-lactamase-mediated resistance but resistance towards these drugs is also on the rise.

  1. PK/PD Optimization in Special Populations

Critically sick patients, newborns, the elderly, and people with renal impairment or increased renal clearance can all have quite different cephalosporin pharmacokinetics. If not carefully managed, these differences could result in toxicity or subtherapeutic levels. Additionally, the absence of reliable PK/PD data in particular populations restricts therapeutic efficacy and makes dose optimization more difficult.

For instance, individuals with increased renal clearance may not be able to maintain %fT > MIC with standard dosage regimens, particularly in intensive care units.

  1. Need for New Generational Advancements

There are still difficulties in fighting complicated infections like Acinetobacter baumannii and carbapenem-resistant Enterobacterales (CRE), even though fifth-generation cephalosporins have broadened their spectrum to cover MRSA and multidrug-resistant Streptococcus pneumoniae. These pathogens must be targeted by future cephalosporin hybrids or analogs with unique mechanisms or enhanced efflux stability.

For instance, ongoing studies on next-generation β-lactamase inhibitors (such zidebactam) and siderophore-conjugated cephalosporins hold out hope for future discoveries.

  1. Diagnostic Stewardship and Precision Therapy

By facilitating early pathogen identification and customized dose, rapid diagnostic testing and therapeutic drug monitoring (TDM) can improve the clinical value of cephalosporins. Cost, accessibility, and infrastructure continue to be barriers to the broad use of such instruments, especially in environments with little resources, such as rural India.

For instance, real-time PK/PD optimization is being studied by integrating real-time MIC data with Bayesian dosing platforms.

  1. Antimicrobial Stewardship

Resistance is still fueled by improper or overuse of cephalosporins. Cephalosporin-specific recommendations must be included in antibiotic stewardship programs (ASPs) in order to support proper medication selection, dosage, and duration based on PK/PD principles and local resistance patterns.

For instance, limiting the use of ceftriaxone in environments where the prevalence of ESBL is increasing has been linked to decreased resistance rates.

CONCLUSION

Across decades, cephalosporins continue to be a vital and adaptable class of β-lactam antibiotics with broad clinical use. The importance of pharmacokinetics (PK) and pharmacodynamics (PD) in directing cephalosporin selection, dosage regimens, and therapeutic efficacy has been emphasized in this study. The antibacterial spectrum, tissue penetration, and resistance stability of cephalosporins have evolved with each generation. Their clinical relevance is wide and expanding, ranging from first-generation compounds used in simple skin infections to fifth-generation medications that are effective against multidrug-resistant organisms like MRSA.

The necessity of appropriate dosage and frequency of administration is highlighted by the time-dependent killing properties of cephalosporins, which are caused by keeping drug concentrations above the minimum inhibitory concentration (%fT > MIC). Additionally, enhancing efficacy while reducing resistance development requires optimizing PK/PD parameters in particular populations, such as critically ill patients, infants, and individuals with renal impairment. Despite their shown effectiveness, cephalosporins are challenged by growing bacterial resistance, uneven clinical application, and a lack of effective treatments for some multidrug-resistant species. Cephalosporin therapy's future hinges on ongoing drug research innovation, the incorporation of quick diagnostic techniques, and an international dedication to antimicrobial stewardship. In conclusion, knowing and using cephalosporin pharmacokinetic and pharmacodynamic principles is crucial for both effective treatment and maintaining the drugs' usefulness in the face of developing germ resistance. Cephalosporins will continue to be a mainstay of antimicrobial therapy for many years to come if their use is judiciously and empirically supported.

REFERENCES

  1. Brotzu G. Ricerche su di un nuovo antibiotico. Boll Ist Sieroter Ital. 1948.
  2. Bush K, Bradford PA. β-Lactams and β-Lactamase Inhibitors: An Overview. Cold Spring Harb Perspect Med. 2016;6(8):a025247.
  3. Papp-Wallace KM, Endimiani A, Taracila MA, Bonomo RA. Carbapenems: Past, Present, and Future. Antimicrob Agents Chemother. 2011;55(11):4943–4960.
  4. Kaye KS, Pogue JM. Infections Caused by Resistant Gram-Negative Bacteria: Epidemiology and Management. Pharmacotherapy. 2015;35(10):949–962.
  5. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 13th ed. Chapter 51: β-Lactam Antibiotics.
  6. Wise R. The pharmacokinetics of the oral cephalosporins—a review. J Antimicrob Chemother. 1990;26(Suppl E):13–20.
  7. Bergan T. Pharmacokinetic properties of the cephalosporins. Drugs. 1987;34(Suppl 2):89–104.
  8. Neu HC. The new β-lactam antibiotics. Springer-Verlag; 1982.
  9. Ambrose PG, Bhavnani SM, Rubino CM, et al. Pharmacokinetics and Pharmacodynamics of Cephalosporins. Clin Pharmacokinet. 2007;46(5):359–377.
  10. Tunkel AR et al. Practice Guidelines for the Management of Bacterial Meningitis. Clin Infect Dis. 2004;39(9):1267–1284.
  11. Bergan T. Pharmacokinetic properties of the cephalosporins. Drugs. 1987;34(Suppl 2):89–104.
  12. Ambrose PG, Bhavnani SM, Rubino CM, et al. Pharmacokinetics and Pharmacodynamics of Cephalosporins. Clin Pharmacokinet. 2007;46(5):359–377.
  13. Pichichero ME. Cephalosporins: a review. Clin Pediatr (Phila). 2005;44(7):573–594.
  14. Tunkel AR, et al. Practice Guidelines for the Management of Bacterial Meningitis. Clin Infect Dis. 2004;39(9):1267–1284.
  15. Nau R, Sörgel F, Eiffert H. Penetration of drugs through the blood–cerebrospinal fluid/blood–brain barrier for treatment of central nervous system infections. Clin Microbiol Rev. 2010;23(4):858–883.
  16. Bush K, Bradford PA. β-Lactams and β-Lactamase Inhibitors: An Overview. Cold Spring Harb Perspect Med. 2016;6(8):a025247.
  17. Papp-Wallace KM et al. Mechanisms of β-Lactam Resistance. Clin Microbiol Rev. 2011;24(3):661–689.
  18. Craig WA. The Pharmacology of Meropenem. Clin Infect Dis. 1997;24(Suppl 2):S266–S275.
  19. Ambrose PG et al. Pharmacodynamics of cephalosporins: time above MIC. Clin Pharmacokinet. 2007;46(5):359–377.
  20. Vogelman B, Gudmundsson S, Leggett J, Turnidge J, Craig WA. Correlation of Antimicrobial Pharmacokinetics and MIC with Therapeutic Efficacy in an Animal Model. J Infect Dis. 1988;158(4):831–847.
  21. Bush K. Proliferation and significance of clinically relevant β-lactamases. Ann N Y Acad Sci. 2013;1277:84–90.
  22. Pichichero ME. Use of selected cephalosporins in penicillin-allergic patients. Drug Saf. 2006;29(4):347–361.
  23. Nau R, Sörgel F, Eiffert H. CSF penetration of antibiotics. Clin Microbiol Rev. 2010;23(4):858–883.
  24. Corey GR, et al. CANVAS 1 and 2 studies of ceftaroline. Lancet Infect Dis. 2010;10(8):525–535.
  25. Tamma PD, Rodriguez-Bano J. β-lactam/β-lactamase inhibitor combinations. Clin Microbiol Rev. 2017;30(1):181–207.
  26. Craig WA. Pharmacokinetics/pharmacodynamics of cephalosporins. Clin Infect Dis. 1997;24(Suppl 1):S1–S10.
  27. Naber KG. Which fluoroquinolones are suitable for treating urinary tract infections? Int J Antimicrob Agents. 2001;17(4):303–313.
  28. Nicolau DP. Optimizing antimicrobial therapy with time-dependent antibiotics. Pharmacotherapy. 2008;28(6 Pt 2):27S–32S.
  29. Nau R, Sörgel F, Eiffert H. Penetration of drugs into the CSF. Clin Microbiol Rev. 2010;23(4):858–883.
  30. Bratzler DW, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J He Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ. Infectious Diseases Society of America Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections. Clin Infect Dis. 2021;72(7):1109–1116.
  31. Falagas ME, Mavroudis AD, Vardakas KZ. The antibiotic pipeline for multidrug-resistant gram-negative bacteria: what can we expect? Expert Rev Anti Infect Ther. 2023;21(2):125–135.
  32. Roberts JA, Abdul-Aziz MH, Lipman J, et al. Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions. Lancet Infect Dis. 2014;14(6):498–509.alth Syst Pharm. 2013;70(3):195–283.
  33. Karaiskos I, Giamarellou H. Siderophore cephalosporins: a promising strategy against multidrug-resistant Gram-negative bacteria. Expert Opin Investig Drugs. 2020;29(1):1–4.
  34. Livermore DM, Mushtaq S, Warner M, Zhang J, Maharjan S, Doumith M. Activity of zidebactam combinations against MBL- and OXA-48-producing Enterobacteriaceae. J Antimicrob Chemother. 2017;72(5):1373–1381.
  35. abdul-Aziz MH, et al. Continuous infusion versus intermittent bolus dosing of β-lactams in critically ill patients. Lancet Infect Dis. 2016;16(8):885–896.
  36. World Health Organization. Global Antimicrobial Resistance and Use Surveillance System (GLASS) Report 2023.

Reference

  1. Brotzu G. Ricerche su di un nuovo antibiotico. Boll Ist Sieroter Ital. 1948.
  2. Bush K, Bradford PA. β-Lactams and β-Lactamase Inhibitors: An Overview. Cold Spring Harb Perspect Med. 2016;6(8):a025247.
  3. Papp-Wallace KM, Endimiani A, Taracila MA, Bonomo RA. Carbapenems: Past, Present, and Future. Antimicrob Agents Chemother. 2011;55(11):4943–4960.
  4. Kaye KS, Pogue JM. Infections Caused by Resistant Gram-Negative Bacteria: Epidemiology and Management. Pharmacotherapy. 2015;35(10):949–962.
  5. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 13th ed. Chapter 51: β-Lactam Antibiotics.
  6. Wise R. The pharmacokinetics of the oral cephalosporins—a review. J Antimicrob Chemother. 1990;26(Suppl E):13–20.
  7. Bergan T. Pharmacokinetic properties of the cephalosporins. Drugs. 1987;34(Suppl 2):89–104.
  8. Neu HC. The new β-lactam antibiotics. Springer-Verlag; 1982.
  9. Ambrose PG, Bhavnani SM, Rubino CM, et al. Pharmacokinetics and Pharmacodynamics of Cephalosporins. Clin Pharmacokinet. 2007;46(5):359–377.
  10. Tunkel AR et al. Practice Guidelines for the Management of Bacterial Meningitis. Clin Infect Dis. 2004;39(9):1267–1284.
  11. Bergan T. Pharmacokinetic properties of the cephalosporins. Drugs. 1987;34(Suppl 2):89–104.
  12. Ambrose PG, Bhavnani SM, Rubino CM, et al. Pharmacokinetics and Pharmacodynamics of Cephalosporins. Clin Pharmacokinet. 2007;46(5):359–377.
  13. Pichichero ME. Cephalosporins: a review. Clin Pediatr (Phila). 2005;44(7):573–594.
  14. Tunkel AR, et al. Practice Guidelines for the Management of Bacterial Meningitis. Clin Infect Dis. 2004;39(9):1267–1284.
  15. Nau R, Sörgel F, Eiffert H. Penetration of drugs through the blood–cerebrospinal fluid/blood–brain barrier for treatment of central nervous system infections. Clin Microbiol Rev. 2010;23(4):858–883.
  16. Bush K, Bradford PA. β-Lactams and β-Lactamase Inhibitors: An Overview. Cold Spring Harb Perspect Med. 2016;6(8):a025247.
  17. Papp-Wallace KM et al. Mechanisms of β-Lactam Resistance. Clin Microbiol Rev. 2011;24(3):661–689.
  18. Craig WA. The Pharmacology of Meropenem. Clin Infect Dis. 1997;24(Suppl 2):S266–S275.
  19. Ambrose PG et al. Pharmacodynamics of cephalosporins: time above MIC. Clin Pharmacokinet. 2007;46(5):359–377.
  20. Vogelman B, Gudmundsson S, Leggett J, Turnidge J, Craig WA. Correlation of Antimicrobial Pharmacokinetics and MIC with Therapeutic Efficacy in an Animal Model. J Infect Dis. 1988;158(4):831–847.
  21. Bush K. Proliferation and significance of clinically relevant β-lactamases. Ann N Y Acad Sci. 2013;1277:84–90.
  22. Pichichero ME. Use of selected cephalosporins in penicillin-allergic patients. Drug Saf. 2006;29(4):347–361.
  23. Nau R, Sörgel F, Eiffert H. CSF penetration of antibiotics. Clin Microbiol Rev. 2010;23(4):858–883.
  24. Corey GR, et al. CANVAS 1 and 2 studies of ceftaroline. Lancet Infect Dis. 2010;10(8):525–535.
  25. Tamma PD, Rodriguez-Bano J. β-lactam/β-lactamase inhibitor combinations. Clin Microbiol Rev. 2017;30(1):181–207.
  26. Craig WA. Pharmacokinetics/pharmacodynamics of cephalosporins. Clin Infect Dis. 1997;24(Suppl 1):S1–S10.
  27. Naber KG. Which fluoroquinolones are suitable for treating urinary tract infections? Int J Antimicrob Agents. 2001;17(4):303–313.
  28. Nicolau DP. Optimizing antimicrobial therapy with time-dependent antibiotics. Pharmacotherapy. 2008;28(6 Pt 2):27S–32S.
  29. Nau R, Sörgel F, Eiffert H. Penetration of drugs into the CSF. Clin Microbiol Rev. 2010;23(4):858–883.
  30. Bratzler DW, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J He Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ. Infectious Diseases Society of America Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections. Clin Infect Dis. 2021;72(7):1109–1116.
  31. Falagas ME, Mavroudis AD, Vardakas KZ. The antibiotic pipeline for multidrug-resistant gram-negative bacteria: what can we expect? Expert Rev Anti Infect Ther. 2023;21(2):125–135.
  32. Roberts JA, Abdul-Aziz MH, Lipman J, et al. Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions. Lancet Infect Dis. 2014;14(6):498–509.alth Syst Pharm. 2013;70(3):195–283.
  33. Karaiskos I, Giamarellou H. Siderophore cephalosporins: a promising strategy against multidrug-resistant Gram-negative bacteria. Expert Opin Investig Drugs. 2020;29(1):1–4.
  34. Livermore DM, Mushtaq S, Warner M, Zhang J, Maharjan S, Doumith M. Activity of zidebactam combinations against MBL- and OXA-48-producing Enterobacteriaceae. J Antimicrob Chemother. 2017;72(5):1373–1381.
  35. abdul-Aziz MH, et al. Continuous infusion versus intermittent bolus dosing of β-lactams in critically ill patients. Lancet Infect Dis. 2016;16(8):885–896.
  36. World Health Organization. Global Antimicrobial Resistance and Use Surveillance System (GLASS) Report 2023.

Photo
Anurag Madhane
Corresponding author

SIRT-Pharmacy , Sanjeev Agrawal Global Educational University BHOPAL 462043

Photo
Dr. Rakhee Kapadia Jain
Co-author

Sanjeev Agrawal Global Educational University BHOPAL

Anurag Madhane*, Dr. Rakhee Kapadia Jain, Comparative Analysis of Cephalosporins: Pharmacokinetics and Pharmacodynamics, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 5, 2494-2502. https://doi.org/10.5281/zenodo.15426195

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