The importance of bactericidal drugs: future directions in infectious disease.

BACKGROUND Although a considerable amount of research has gone into the study of the role of bactericidal versus bacteriostatic antimicrobial agents in the treatment of different infectious diseases, there is no accepted standard of practice. METHODS A panel of infectious diseases specialists reviewed the available literature to try to define specific recommendations for clinical practice. RESULTS In infections of the central nervous system, the rapidity with which the organism is killed may be an important determinant, because of the serious damage that may occur during these clinical situations. The failure of bacteriostatic antibiotics to adequately treat endocarditis is well documented, both in human studies and in animal models. CONCLUSION The bulk of the evidence supports the concept that, in treating endocarditis and meningitis, it is important to use antibacterial agents with in vitro bactericidal activity. This conclusion is based on both human and animal data. The data to support bactericidal drugs' superiority to bacteriostatic drugs do not exist for most other clinical situations, and animal models do not support this concept in some situations. Clinicians should be aware that drugs that are bacteriostatic for one organism may in fact be bactericidal for another organism or another strain of the same organism.

[1]  Bristowe Js An Address on the Early Recognition of General Paralysis of the Insane, and the Relations between this Disease, Tabes Dorsalis, and Disseminated Sclerosis. , 2022 .

[2]  E. Hull,et al.  SULFONAMIDE THERAPY OF BACTERIAL ENDOCARDITIS; RESULTS IN 42 CASES , 1943 .

[3]  R. Christie Penicillin in Subacute Bacterial Endocarditis , 1946, British medical journal.

[4]  E. Jawetz,et al.  The Combined Action of Penicillin with Streptomycin or Chloromycetin on Enterococci in Vitro. , 1950, Science.

[5]  T. Hunter Speculations on the mechanism of cure of bacterial endocarditis. , 1950, Journal of the American Medical Association.

[6]  H. Dowling,et al.  Treatment of pneumococcic meningitis with penicillin compared with penicillin plus aureomycin; studies including observations on an apparent antagonism between penicillin and aureomycin. , 1951, A.M.A. archives of internal medicine.

[7]  J. Burke The effective period of preventive antibiotic action in experimental incisions and dermal lesions. , 1961, Surgery.

[8]  P. Wehrle,et al.  Antibiotic antagonism in bacterial meningitis. , 1967, Antimicrobial Agents and Chemotherapy.

[9]  L. Biró,et al.  Study of bactericidal and bacteriostatic antibiotics in animals with normal and suppressed immunity. , 1968, Chemotherapia.

[10]  E. Hook,et al.  Enterococcal endocarditis. An analysis of 38 patients observed at the New York Hospital-Cornell Medical Center. , 1970, Archives of internal medicine.

[11]  W Satterlee,et al.  Empiric therapy with carbenicillin and gentamicin for febrile patients with cancer and granulocytopenia. , 1971, The New England journal of medicine.

[12]  H. Welshimer,et al.  Listeria monocytogenes in nature. , 1971, Applied microbiology.

[13]  G. Bodey,et al.  Infections in cancer patients. Results with gentamicin sulfate therapy , 1972, Cancer.

[14]  A. Weinstein,et al.  Penicillin and gentamicin therapy for enterococcal infections. , 1973, JAMA.

[15]  R. Gleckman Trimethoprim-sulfamethoxazole vs ampicillin in chronic urinary tract infections. A double-blind multicenter cooperative controlled study. , 1975, JAMA.

[16]  C. Norden Experimental osteomyelitis. IV. Therapeutic trials with rifampin alone and in combination with gentamicin, sisomicin, and cephalothin. , 1975, The Journal of infectious diseases.

[17]  J. Klastersky,et al.  Comparative effectiveness of combinations of amikacin with penicillin G and amikacin with carbenicillin in gram-negative septicemia: double-blind clinical trial. , 1976, The Journal of infectious diseases.

[18]  S. Mize,et al.  A controlled study of intrathecal antibiotic therapy in gram-negative enteric meningitis of infancy. Report of the neonatal meningitis cooperative study group. , 1976, The Journal of pediatrics.

[19]  D. Kaye,et al.  Antibiotic Concentrations in Serum, Serum Bactericidal Activity, and Results of Therapy of Streptococcal Endocarditis in Rabbits , 1977, Antimicrobial Agents and Chemotherapy.

[20]  F. Fekety,et al.  Experimental endocarditis due to Pseudomonas aeruginosa. II. Therapy with carbenicillin and gentamicin. , 1977, The Journal of infectious diseases.

[21]  M. Sande,et al.  Response to therapy in an experimental rabbit model of meningitis due to Listeria monocytogenes. , 1979, The Journal of infectious diseases.

[22]  R. Tight Ampicillin therapy of experimental enterococcal endocarditis , 1980, Antimicrobial Agents and Chemotherapy.

[23]  R. Horwitz,et al.  Association between serum inhibitory and bactericidal concentrations and therapeutic outcome in bacterial endocarditis. , 1982, American Journal of Medicine.

[24]  J. Lilleyman,et al.  Ceftazidime as a single agent in the management of children with fever and neutropenia. , 1983, The Journal of antimicrobial chemotherapy.

[25]  C. Norden,et al.  Treatment of experimental chronic osteomyelitis due to staphylococcus aureus with vancomycin and rifampin. , 1983, The Journal of infectious diseases.

[26]  L. Devriese,et al.  Susceptibility of clostridia from farm animals to 21 antimicrobial agents including some used for growth promotion. , 1983, Journal of Antimicrobial Chemotherapy.

[27]  R. Eng,et al.  Examination of gram-negative bacilli from meningitis patients who failed or relapsed on moxalactam therapy , 1984, Antimicrobial Agents and Chemotherapy.

[28]  J. Ryan,et al.  Optimal therapy for enterococcal endocarditis. , 1984, The American journal of medicine.

[29]  J. Sculier,et al.  Significance of serum bactericidal activity in gram-negative bacillary bacteremia in patients with and without granulocytopenia. , 1984, The American journal of medicine.

[30]  J. S. Wolfson,et al.  Drug therapy. Serum bactericidal activity as a monitor of antibiotic therapy. , 1985, The New England journal of medicine.

[31]  G. Bodey Synergy. Should it determine antibiotic selection in neutropenic patients? , 1985, Archives of Internal Medicine.

[32]  G. Drusano,et al.  Potential of imipenem as single-agent empiric antibiotic therapy of febrile neutropenic patients with cancer. , 1985, The American journal of medicine.

[33]  A. Iravani,et al.  Single-dose ceftriaxone versus multiple-dose trimethoprim-sulfamethoxazole in the treatment of acute urinary tract infections , 1985, Antimicrobial Agents and Chemotherapy.

[34]  C. Stratton,et al.  Multicenter collaborative evaluation of a standardized serum bactericidal test as a prognostic indicator in infective endocarditis. , 1985, The American journal of medicine.

[35]  L. Reller The serum bactericidal test. , 1986, Reviews of infectious diseases.

[36]  J. Klastersky Concept of empiric therapy with antibiotic combinations. Indications and limits. , 1986, American Journal of Medicine.

[37]  H. Feder Chloramphenicol: what we have learned in the last decade. , 1986, Southern medical journal (Birmingham, Ala. Print).

[38]  C. Stratton,et al.  Multicenter collaborative evaluation of a standardized serum bactericidal test as a predictor of therapeutic efficacy in acute and chronic osteomyelitis. , 1987, The American journal of medicine.

[39]  G. Eliopoulos,et al.  Antimicrobial susceptibility tests and their role in therapeutic drug monitoring. , 1987, Clinics in Laboratory Medicine.

[40]  D. Longo,et al.  A Randomized Trial Comparing Ceftazidime Alone With Combination Antibiotic Therapy in Cancer Patients With Fever and Neutropenia , 1987 .

[41]  J. Larrick,et al.  Antibiotic therapy, endotoxin concentration in cerebrospinal fluid, and brain edema in experimental Escherichia coli meningitis in rabbits. , 1987, The Journal of infectious diseases.

[42]  M. Ipp,et al.  MULTICENTER COLLABORATIVE EVALUATION OF A STANDARDIZED SERUM BACTERICIDAL TEST AS A PREDICTOR OF THERAPEUTIC EFFICACY IN ACUTE AND CHRONIC OSTEOMYELITIS , 1988 .

[43]  P. Trieu-Cuot,et al.  Mechanism of action of spiramycin and other macrolides. , 1988, The Journal of antimicrobial chemotherapy.

[44]  L. Bush,et al.  Pharmacodynamics of antimicrobial agents. Bactericidal and postantibiotic effects. , 1989, Infectious Disease Clinics of North America.

[45]  G. Eliopoulos,et al.  Synergism and antagonism. , 1989, Infectious disease clinics of North America.

[46]  T. Calandra,et al.  Prospective randomized evaluation of ciprofloxacin versus piperacillin plus amikacin for empiric antibiotic therapy of febrile granulocytopenic cancer patients with lymphomas and solid tumors. The European Organization for Research on Treatment of Cancer International Antimicrobial Therapy Cooperati , 1991, Antimicrobial Agents and Chemotherapy.

[47]  B. J. Geiman,et al.  Dexamethasone and bacterial meningitis. A meta-analysis of randomized controlled trials. , 1992, Western Journal of Medicine.

[48]  H. Gnehm,et al.  Dexamethasone therapy for bacterial meningitis in children , 1993, The Lancet.

[49]  H. Gnehm,et al.  Dexamethasone therapy for bacterial meningitis in children. Swiss Meningitis Study Group. , 1993, Lancet.

[50]  E. Kuijper,et al.  Antibiotic-induced endotoxin release in patients with gram-negative urosepsis: a double-blind study comparing imipenem and ceftazidime. , 1995, The Journal of infectious diseases.

[51]  M. McIntosh Dexamethasone therapy for children with bacterial meningitis , 1995 .

[52]  S. Steinberg,et al.  Monotherapy for fever and neutropenia in cancer patients: a randomized comparison of ceftazidime versus imipenem. , 1995, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[53]  S. Kaplan,et al.  Dexamethasone therapy for children with bacterial meningitis. Meningitis Study Group. , 1995, Pediatrics.

[54]  J. Aparicio,et al.  Randomised comparison of ceftazidime and imipenem as initial monotherapy for febrile episodes in neutropenic cancer patients. , 1996, European Journal of Cancer.

[55]  M. Paesmans,et al.  Monotherapy with meropenem versus combination therapy with ceftazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer. The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer and the Gruppo Itali , 1996, Antimicrobial agents and chemotherapy.

[56]  D. Hoelzer,et al.  Prospective randomized study to compare imipenem 1.5 grams per day vs. 3.0 grams per day in infections of granulocytopenic patients. , 1998, Journal of Infection.

[57]  T. Elliott,et al.  Evaluation of the in-vitro activity of the glycopeptide antibiotic LY333328 in comparison with vancomycin and teicoplanin. , 1998, The Journal of antimicrobial chemotherapy.

[58]  J. Smilack THE TETRACYCLINES , 1967, Mayo Clinic proceedings.

[59]  Jerome J. Schentag Antimicrobial action and pharmacokinetics/pharmacodynamics: the use of AUIC to improve efficacy and avoid resistance. , 1999, Journal of chemotherapy.

[60]  I. Raad,et al.  Prospective, Randomized Dose-Ranging Open Phase II Pilot Study of Quinupristin/Dalfopristin versus Vancomycin in the Treatment of Catheter-Related Staphylococcal Bacteremia , 1999, European Journal of Clinical Microbiology and Infectious Diseases.

[61]  V. Yu,et al.  Combination antibiotic therapy versus monotherapy for gram-negative bacteraemia: a commentary. , 1999, International journal of antimicrobial agents.

[62]  M. González,et al.  Bacteremic pneumonia due to Staphylococcus aureus: A comparison of disease caused by methicillin-resistant and methicillin-susceptible organisms. , 1999, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[63]  Jerry D. Smilack,et al.  Symposium on Antimicrobial Agents—Part XThe Tetracyclines , 1999 .

[64]  E. Quinlivan,et al.  Mechanism of the antimicrobial drug trimethoprim revisited , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[65]  F. Tally,et al.  Development of daptomycin for gram-positive infections. , 2000, The Journal of antimicrobial chemotherapy.

[66]  M. Levison Pharmacodynamics of antibacterial drugs. , 2000, Infectious disease clinics of North America.

[67]  T. Fabian,et al.  Treatment of gram-positive nosocomial pneumonia. Prospective randomized comparison of quinupristin/dalfopristin versus vancomycin. Nosocomial Pneumonia Group. , 2000, American journal of respiratory and critical care medicine.

[68]  A. Tunkel,et al.  Antibacterial agents in infections of the central nervous system. , 2000, Infectious disease clinics of North America.

[69]  A. Keating,et al.  Meropenem versus ceftazidime in the treatment of cancer patients with febrile neutropenia: a randomized, double-blind trial. , 2000, Journal of Clinical Oncology.

[70]  E Rubinstein,et al.  Linezolid (PNU-100766) versus vancomycin in the treatment of hospitalized patients with nosocomial pneumonia: a randomized, double-blind, multicenter study. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[71]  A. MacGowan Role of pharmacokinetics and pharmacodynamics: does the dose matter? , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[72]  E. Mylonakis,et al.  Infective endocarditis in adults. , 2001, The New England journal of medicine.

[73]  J. Rotschafer,et al.  What Do We Really Know About Antibiotic Pharmacodynamics? , 2001, Pharmacotherapy.

[74]  R. Hancock,et al.  Cationic peptides: effectors in innate immunity and novel antimicrobials. , 2001, The Lancet. Infectious diseases.

[75]  D. Hooper,et al.  Mechanisms of action of antimicrobials: focus on fluoroquinolones. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[76]  R. Akins,et al.  Bactericidal Activities of Two Daptomycin Regimens against Clinical Strains of Glycopeptide Intermediate-ResistantStaphylococcus aureus, Vancomycin-ResistantEnterococcus faecium, and Methicillin-ResistantStaphylococcus aureus Isolates in an In Vitro Pharmacodynamic Model with Simulated Endocardial V , 2001, Antimicrobial Agents and Chemotherapy.

[77]  W. Burman,et al.  Comparative Pharmacokinetics and Pharmacodynamics of the Rifamycin Antibacterials , 2001, Clinical pharmacokinetics.

[78]  C. John,et al.  Spinal epidural abscesses in children: a 15-year experience and review of the literature. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[79]  Ronald N. Jones,et al.  Oxazolidinone antibiotics , 2001, The Lancet.

[80]  R. Nau,et al.  Modulation of Release of Proinflammatory Bacterial Compounds by Antibacterials: Potential Impact on Course of Inflammation and Outcome in Sepsis and Meningitis , 2002, Clinical Microbiology Reviews.

[81]  P. Mead,et al.  Antimicrobial therapy in patients with Escherichia coli O157:H7 infection. , 2002, JAMA.

[82]  J. K. Gibson,et al.  Time-dependent antibacterial effects of linezolid in experimental rabbit endocarditis. , 2002, The Journal of antimicrobial chemotherapy.

[83]  Weber Antimicrobial Therapy and Vaccines , 2002 .

[84]  M. Rybak,et al.  Influences of Linezolid, Penicillin, and Clindamycin, Alone and in Combination, on Streptococcal Pyrogenic Exotoxin A Release , 2003, Antimicrobial Agents and Chemotherapy.

[85]  W. Binder,et al.  Dexamethasone in adults with bacterial meningitis. , 2003, The New England journal of medicine.