Effective Combination Therapy for Invasive Pneumococcal Pneumonia with Ampicillin and Intravenous Immunoglobulins in a Mouse Model

Hennezel, Laetitia De; Ramisse, Françoise; Binder, Patrice; Marchal, G; Alonso, Jean-Michel

doi:10.1128/aac.45.1.316-318.2001

Cited by 24 publications

(19 citation statements)

References 29 publications

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“…The alteration of the cell surface by the ␤-lactam, which allows opsonization and phagocytosis (7,19), overcomes the capsular impediment for recognition of C3b on the bacterial surface by polymorphonuclear cells. In a recently published study (3), the combination of immunoglobulins and an aminopenicillin was fully protective in an invasive pneumococcal pneumonia model of infection with a penicillin-susceptible serotype 3 strain in mice.…”

Section: Discussionmentioning

confidence: 99%

Effects of Specific Antibodies against Streptococcus pneumoniae on Pharmacodynamic Parameters of β-Lactams in a Mouse Sepsis Model

Casal

Aguilar

Jado

et al. 2002

Antimicrob Agents Chemother

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A dose-ranging study to investigate the in vivo effects of the presence of specific antibodies on the efficacy of ␤-lactam treatment of sepsis caused by Streptococcus pneumoniae (non-␤-lactam-susceptible serotype 6B isolate) was performed with a BALB/c mouse model. Hyperimmune serum was obtained from mice immunized with the heat-inactivated strain. The rate of mortality was 100% in nontreated animals in the absence of specific antibodies. A single injection of a one-half or one-quarter dilution of hyperimmune serum produced 60 to 40% survival rates. In the absence of specific antibodies, the minimal effective doses of amoxicillin and cefotaxime that produced survival rates of 100 and 80% were 25 and 50 mg/kg of body weight (three times a day for up to six doses), respectively. These doses produced times that the levels in serum remained above the MIC (⌬T > MICs) Ϸ30% of the dosing interval. When specific antibodies were present (by administration of a one-half or one-quarter dilution of hyperimmune serum), the minimal effective doses of the antibiotics were 3.12 and 6.25 mg/kg (Ϸ8 times lower), with the ⌬T > MICs being approximately 3 and 5% of the dosing interval for amoxicillin and cefotaxime, respectively. This in vivo combined pharmacodynamic effect offers possibilities that can be used to address penicillin resistance.Evidence shows that the successful outcome of infections caused by Streptococcus pneumoniae in humans depends on the humoral arm of the immune system and on treatment with an adequate antibiotic. Immunogenicity depends on the pneumococcal serotype (11). Evidence of the participation of immunogenicity in the outcome is based on the spontaneous resolution of fever in the absence of treatment at the time that capsular antibodies appear (15) and the increase in the severities of infections when immunoglobulin G2 (IgG2) (10) or C3 complement (4) deficiencies are present.Colonization with S. pneumoniae is an immunizing event. In the absence of conditions that predispose an individual to infection, antibodies to the capsular polysaccharide of a colonizing organism are likely to appear before infection (15). The presence of anticapsular antibodies is regarded as a generally good, but not ideal, surrogate marker of immunity; the absence of such antibodies probably indicates a relative degree of susceptibility, even though many other factors contribute to protection against pneumococcal disease (15). In these circumstances, the appearance of pneumococcal sepsis indicates defective protection against pneumococcal invasion.The administration of serum containing type-specific antibodies in the preantibiotic era was only moderately effective for the treatment of pneumococcal pneumonia (15) and was largely supplanted by the administration of antibiotics. Empirical antibiotic treatment should be chosen by consideration of data from susceptibility surveillance studies (1), antibiotic susceptibility profiles for isolates of a particular serotype (5, 6, 13), serotype distribution (5, 6, 13), and the disease bein...

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Section: Discussionmentioning

confidence: 99%

Effects of Specific Antibodies against Streptococcus pneumoniae on Pharmacodynamic Parameters of β-Lactams in a Mouse Sepsis Model

Casal

Aguilar

Jado

et al. 2002

Antimicrob Agents Chemother

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“…More recently, IVIg has been shown to protect mice against pneumococcal pneumonia but failed to prevent bacteremia; however, IVIg-administered in combination with ampicillin was found to be fully protective (10).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, hdIVIg, given at 2 g/kg/month and used as an immunomodulatory agent, was first described for immune-mediated thrombocytopenia (18) but is now widely used in treating a range of neurological, hematological, immunological, dermatological, and rheumatological immune and inflammatory disorders (29). Recently, the use of IVIg as an anti-infectious agent in viral and bacterial infections has been reviewed (4), and it has been demonstrated that IVIg given in combination with ampicillin is protective against pneumococcal pneumonia (10). In this study, we investigated the capacity of hdIVIg to influence the course of infection in a murine model of TB.…”

mentioning

confidence: 99%

Therapeutic Efficacy of High-Dose Intravenous Immunoglobulin inMycobacterium tuberculosisInfection in Mice

Roy¹,

Stavropoulos²,

Brennan³

et al. 2005

Infect Immun

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cells. Analysis of T cells infiltrating the lungs revealed only small increases in CD8؉ but not CD4 ؉ T-cell numbers in hdIVIg-treated mice. The mechanism of action of hdIVIg against tuberculosis in mice remains to be determined. Nevertheless, since hdIVIg is already widely used clinically, the magnitude and long duration of the therapeutic effect seen here suggest that IVIg, or components of it, may find ready application as an adjunct to therapy of human tuberculosis.

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“…Cependant, les effets observés dans certains essais cliniques sont parfois discordants [10,11] (Tableau I), car les IVIG sont des mélanges d'IgG provenant des plasmas de milliers de donneurs et leur composition peut varier d'un fabricant à l'autre et de lot à lot [8]. De plus, la proportion d'anticorps spécifiques d'un type antigénique d'un pathogène que l'on veut neutraliser peut ne pas excéder 1% du titre en IgG d'une prépa-ration d'IVIG [16]. Ces aléas dans la composition des IVIG sont en partie corrigés dans les préparations d'IVIG hyperimmunes obtenues à partir de donneurs dont les sérums ont un titre élevé d'anticorps contre un pathogène considéré.…”

Section: Immunothérapie Passive Des Infections Respiratoires Par Immuunclassified

“…Ce mécanisme de neutralisation est efficace contre les pathogènes extracellulaires ou la dissémination intercellulaire des pathogènes intracellulaires, mais est inefficace contre les virus intracellulaires [20,21]. Expérimentalement, la demi-vie des IVIG dans les fluides pulmonaires non inflammatoires de la souris est de 48 heures contre 7jours dans le sang après injection intraveineuse, et les IVIG administrées par voie intranasale ne sont pas détectables dans le sang [16]. voie veineuse.…”

Section: Immunothérapie Des Infections Respiratoires Par Administratiunclassified

Immunoprophylaxie des infections respiratoires

2004

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Effective Combination Therapy for Invasive Pneumococcal Pneumonia with Ampicillin and Intravenous Immunoglobulins in a Mouse Model

Cited by 24 publications

References 29 publications

Effects of Specific Antibodies against Streptococcus pneumoniae on Pharmacodynamic Parameters of β-Lactams in a Mouse Sepsis Model

Effects of Specific Antibodies against Streptococcus pneumoniae on Pharmacodynamic Parameters of β-Lactams in a Mouse Sepsis Model

Therapeutic Efficacy of High-Dose Intravenous Immunoglobulin inMycobacterium tuberculosisInfection in Mice

Immunoprophylaxie des infections respiratoires

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