rifampin and Pseudomonas-Infections

Topics: Amikacin; Anti-Bacterial Agents; Bacterial Infections; Cerebrospinal Fluid Shunts; Drug Resistance, Microbial; Drug Therapy, Combination; Escherichia coli Infections; Gentamicins; Humans; Injections, Intravenous; Injections, Intraventricular; Klebsiella Infections; Leukocytes; Meningitis; Premedication; Pseudomonas Infections; Reoperation; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis; Tobramycin; Vancomycin

The literature on the clinical use of rifampicin in combination for the treatment of non-mycobacterial diseases is reviewed. From the published evidence, the most promising associations are, for staphylococcal infections, gentamicin, erythromycin, kanamycin and fusidic acid. In the field of Gram-negative infections, Psuedomonas-induced sepsis in particular, data are not so impressive but promising results have been obtained with the associated use of rifampicin and gentamicin or colistin. Some systemic fungal diseases may be successfully treated with rifampicin in combination with amphotericin-B. Although only few reports are available on this subject, the importance of such an application is stressed in view of the severity of these diseases and of the lack of appropriate treatments.

Topics: Amphotericin B; Cephalosporins; Chloramphenicol; Colistin; Drug Therapy, Combination; Endocarditis, Bacterial; Erythromycin; Gentamicins; Humans; Kanamycin; Lincomycin; Mycoses; Nalidixic Acid; Penicillins; Pseudomonas Infections; Respiratory Tract Infections; Rifampin; Staphylococcal Infections; Sulfamethoxazole; Tetracyclines; Trimethoprim; Urinary Tract Infections; Vancomycin

Topics: Anti-Bacterial Agents; Anti-Infective Agents, Urinary; Bacteriuria; Cephalosporins; Chloramphenicol; Culture Media; Cycloserine; Cystitis; Erythromycin; Escherichia coli Infections; Gentamicins; Hemagglutination Tests; Humans; Kanamycin; Methenamine; Methods; Nalidixic Acid; Nitrofurantoin; Penicillins; Polymyxins; Pseudomonas Infections; Pyelonephritis; Rifampin; Streptomycin; Sulfonamides; Tetracycline; Trimethoprim; Urinary Tract Infections

Topics: Adult; Anti-Bacterial Agents; Cephaloridine; Enterobacteriaceae Infections; Fusidic Acid; Gentamicins; Humans; Infant; Infections; Lincomycin; Nalidixic Acid; Penicillin Resistance; Penicillins; Pseudomonas Infections; Respiratory Tract Infections; Rifampin; Sulfamethoxazole; Tuberculosis; Urinary Tract Infections

We retrospectively evaluated the safety and effectiveness of colistin alone or in combination with other antimicrobials in eight diabetic patients with severe diabetic foot infections due to multidrug resistant (MDR) Pseudomonas aeruginosa, complicated in 4 cases by osteomyelitis. All patients received colistin after other ineffective antimicrobial treatment, when MDR P. aeruginosa strains were isolated by cultural examination and together with a multidisciplinary care approach including revascularization, surgical debridement and adequate offloading. The mean duration of therapy was 72 +/- 52.9 days. Six out of 8 patients (75%) successfully benefited from colistin therapy, while 2 patients failed and/or experienced side effects that led to discontinuation of therapy. Serious adverse events (i.e. acute renal failure and pulmonary edema) were observed in 1 patient. Our data allow us to conclude that colistin, alone or in combination with other antimicrobials, is safe and effective when administered as part of a multidisciplinary approach, to promote healing of diabetic foot infection due to MDR P. aeruginosa.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Combined Modality Therapy; Debridement; Diabetic Foot; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Middle Aged; Osteomyelitis; Pseudomonas Infections; Retrospective Studies; Rifampin; Treatment Outcome

A multicenter, prospective randomized trial was conducted to determine if the addition of rifampin to a combination therapy of an antipseudomonal beta-lactam agent and aminoglycoside improves the outcome of patients with Pseudomonas aeruginosa bacteremia. The Zelen protocol for randomized-consent design was used. Consent was sought only from patients randomized to the experimental therapy (rifampin+). If the experimental therapy was refused, the patient would then receive the standard combination therapy (control); however, when outcome was evaluated, all patients randomized to the rifampin+ group, including those that declined rifampin, were compared with the control group. One hundred twenty-one consecutive hospitalized patients with positive blood cultures for P. aeruginosa were enrolled. Entry was stratified for prior use of empiric antipseudomonal antibiotics, neutropenia, severity of illness, and presence of pneumonia. Fifty-eight patients were randomized to receive rifampin (600 mg orally every 8 h for the first 72 h and then every 12 h for a total of 10 days) plus a beta-lactam agent plus an aminoglycoside. Sixty-three received the standard therapy of a beta-lactam plus an aminoglycoside agent (control). Bacteriologic cure occurred significantly more frequently in patients randomized to the rifampin+ regimen. Breakthrough or relapsing bacteremias occurred in 2% of the three-drug (rifampin+) group, compared with 14% for the two-drug (standard therapy) group. Despite this favorable trend in bacteriological response, no significant differences in survival were seen for the two treatment groups. Rifamycin derivatives warrant further clinical study as antipseudomonal agents. The Zelen protocol appears well suited for comparative trials of antimicrobial agents.

Topics: Aged; Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Drug Therapy, Combination; Humans; Middle Aged; Penicillins; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Severity of Illness Index

The emergence of multidrug-resistant Pseudomonas aeruginosa infections has urged the need to find new strategies, such as the use of combinations of antibiotics. Among these, the combination of colistin with other antibiotics has been studied. Here, the action of combinations of colistin and rifampicin on both planktonic and sessile cells of colistin-resistant P. aeruginosa was studied. Dynamic biofilms were formed and treated with such a combination, resulting in an active killing effect of both colistin-resistant and colistin-susceptible P. aeruginosa in biofilms. The results suggest that the action of colistin on the outer membrane facilitates rifampicin penetration, regardless of the colistin-resistant phenotype. Based on these

Topics: Anti-Bacterial Agents; Biofilms; Colistin; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin

Pseudomonas aeruginosa is a leading cause of corneal infections. Recently, we discovered an antimicrobial drug combination, polymyxin B/trimethoprim (PT) + rifampin, that displayed impressive efficacy toward P. aeruginosa in both in vitro and in vivo studies. As such, this combination was further evaluated as a potential keratitis therapeutic through testing the combination's efficacy against a diverse set of P. aeruginosa clinical isolates.. Minimum inhibitory concentrations (MICs) of moxifloxacin, levofloxacin, erythromycin, tobramycin, PT, polymyxin B (alone), trimethoprim (alone), and rifampin were determined for 154 ocular clinical P. aeruginosa isolates, 90% of which were derived from corneal scrapings. Additionally, the efficacy of PT + rifampin was evaluated utilizing fractional inhibitory concentration (FIC) testing.. While 100% of isolates were resistant to erythromycin (average MIC 224 ± 110 µg·mL-1) and trimethoprim (alone) (206 ± 67.3 µg·mL-1), antibiotic resistance was generally found to be low: moxifloxacin (2% of isolates resistant; average MIC 1.08 ± 1.61 µg·mL-1), levofloxacin (3.9%; 1.02 ± 2.96 µg·mL-1), tobramycin (1%; 0.319 ± 1.31 µg·mL-1), polymyxin B (0%; 0.539 ± 0.206 µg·mL-1), PT (0%; 0.416 ± 0.135 µg·mL-1), and rifampin (0%; 23.4 ± 6.86 µg·mL-1). Additionally, FIC testing revealed that PT + rifampin eradicated 100% of isolates demonstrating additive or synergistic activity in 95% of isolates (average FIC index 0.701 ± 0.132).. The drug combination of PT + rifampin was effective against a large panel of clinically relevant P. aeruginosa strains and, as such, may represent a promising therapeutic for P. aeruginosa keratitis.. This work furthers the preclinical development of a novel antibiotic combination for the treatment of corneal infections (bacterial keratitis).

Topics: Anti-Bacterial Agents; Bacitracin; Drug Combinations; Erythromycin; Framycetin; Humans; Keratitis; Levofloxacin; Moxifloxacin; Polymyxin B; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Tobramycin; Trimethoprim

Infections caused by multidrug-resistant

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Biofilms; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Peptides; Polymers; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin

The increasing prevalence of carbapenem-resistant Pseudomonas aeruginosa (CRPA) strains in the hospital setting represents an emerging challenge to clinical treatment for Pseudomonas aeruginosa (PA) infections, as the range of therapeutic agents active against these pathogens becomes increasingly constrained. This study demonstrated for the first time that fosfomycin (FOS) combined with rifampin (RIF) showed strong synergistic effects against CRPA and carbapenem-susceptible PA, with 100% synergistic rates. Additionally, the time-killing curve further proves the dynamic antibacterial activity of FOS + RIF against CRPA. Further experiments determined that antibacterial mechanisms of FOS + RIF might be inhibition of biofilm formation and eradication of preformed biofilm. The results of the inhibition biofilm formation assay demonstrated that RIF and FOS at 1/8MIC, 1/16MIC and 1/32MIC have better inhibitory effects on CRPA biofilm formation VS FOS alone (96, 90 and 78% vs 29, 24 and 22%) (P < 0·0001) or RIF alone (96, 90 and 78% vs 86, 67 and 29%) (P < 0·01). The rates of eradicating preformed biofilm with combination therapy at 1/2MIC, 1/4MIC and 1/8MIC of both antibiotics, increased 46, 61 and 55% compared with FOS alone (P < 0·001) and 37, 33 and 46% compared with RIF alone (P < 0·01). This finding will provide new insights into the treatment of bacterial infections caused by CRPA, which can be further explored in clinical practice.

Topics: Anti-Bacterial Agents; Biofilms; Carbapenems; Fosfomycin; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin

Topics: Adult; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Gentamicins; Humans; Male; Meropenem; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Urinary Tract Infections

Topics: Animals; Anti-Bacterial Agents; Cornea; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Eye Infections, Bacterial; Female; Humans; Keratitis; Mice; Mice, Inbred BALB C; Moxifloxacin; Ophthalmic Solutions; Polymyxin B; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome; Trimethoprim

Hypermutable

Topics: Adult; Anti-Bacterial Agents; Australia; Bacterial Proteins; Cystic Fibrosis; Drug Resistance, Microbial; Humans; Mutation; Phylogeny; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin

Bacterial keratitis causes significant blindness, yet antimicrobial resistance has rendered current treatments ineffective. Polymyxin B-trimethoprim (PT) plus rifampin has potent

Topics: Animals; Anti-Bacterial Agents; Cornea; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Eye Infections, Bacterial; Female; Keratitis; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Polymyxin B; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Trimethoprim

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) infections represent a major therapeutic problem and combination therapy may be the chemotherapeutic option.. Bioluminescent CRPA was developed through sequential subcultures in subinhibitory concentrations of meropenem from an engineered strain of bioluminescent PA Xen5. Then CRPA was injected intraperitoneally to establish an intraperitoneal murine infection model. Treatments of colistin alone or combined with rifampicin or meropenem were started 1 h after infection. In vivo bioluminescence imaging was applied dynamically at 0 h, and 2 and 5 h after treatment. Ex vivo bacterial counts from liver, kidney, spleen, lung and blood samples were also determined 5 h after treatment.. In vivo imaging showed that both low- and high-dose colistin combined with rifampicin resulted in a significant decrease in bioluminescence signals compared with monotherapy of colistin or rifampicin alone, whereas colistin and meropenem combination therapy did not show a greater bactericidal effect compared with monotherapy. Ex vivo bacterial count results also confirmed that combination of both low- and high-dose colistin with rifampicin resulted in significantly reduced colony counts from five kinds of tissue samples. However, only combination of high-dose colistin + meropenem resulted in reduced colony counts merely in lung and blood samples.. Compared with single drugs, colistin and rifampicin combination therapy could exert synergistic effects, which might provide a better alternative when treating CRPA infections in clinical practice. Combination of colistin and meropenem should be considered with caution because it barely shows any synergism in the present in vivo model.

Topics: Animal Structures; Animals; Anti-Bacterial Agents; Bacterial Load; beta-Lactam Resistance; Colistin; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Female; Intraabdominal Infections; Luminescent Measurements; Meropenem; Mice, Inbred BALB C; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Staining and Labeling; Treatment Outcome

Rifampicin potentiates the activity of aminoglycosides (AGs) versus Pseudomonas aeruginosa by targeting the AmgRS two-component system. In this study we examine the impact of rifampicin on the AG susceptibility of cystic fibrosis (CF) lung isolates of P. aeruginosa and the contribution of AmgRS to AG resistance in these isolates.. amgR deletion derivatives of clinical isolates were constructed using standard gene replacement technology. Susceptibility to AGs ± rifampicin (at ½ MIC) was assessed using a serial 2-fold dilution assay.. Rifampicin showed a variable ability to potentiate AG activity versus the CF isolates, enhancing AG susceptibility between 2- and 128-fold. Most strains showed potentiation for at least two AGs, with only a few strains showing no AG potentiation by rifampicin. Notably, loss of amgR increased AG susceptibility although rifampicin potentiation of AG activity was still observed in the ΔamgR derivatives.. AmgRS contributes to AG resistance in CF isolates of P. aeruginosa and rifampicin shows a variable ability to potentiate AG activity against these, highlighting the complexity of AG resistance in such isolates.

Topics: Aminoglycosides; Anti-Bacterial Agents; Cystic Fibrosis; Drug Synergism; Gene Knockout Techniques; Genes, Bacterial; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin

Hydraphiles are synthetic amphiphiles that form ion-conducting pores in liposomal membranes. These pores exhibit open-close behavior when studied by planar bilayer conductance techniques. In previous work, we showed that when co-administered with various antibiotics to the DH5α strain of Escherichia coli, they enhanced the drug's potency. We report here potency enhancements at low concentrations of hydraphiles for the structurally and mechanistically unrelated antibiotics erythromycin, kanamycin, rifampicin, and tetracycline against Gram negative E. coli (DH5α and K-12) and Pseudomonas aeruginosa, as well as Gram positive Bacillus subtilis. Earlier work suggested that potency increases correlated to ion transport function. The data presented here comport with the function of hydraphiles to enhance membrane permeability in addition to, or instead of, their known function as ion conductors.

Topics: Anti-Bacterial Agents; Bacillus subtilis; Erythromycin; Escherichia coli; Escherichia coli Infections; Humans; Kanamycin; Microbial Sensitivity Tests; Permeability; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Surface-Active Agents; Tetracycline

A screen for agents that potentiated the activity of paromomycin (PAR), a 4,5-linked aminoglycoside (AG), against wild-type Pseudomonas aeruginosa identified the RNA polymerase inhibitor rifampin (RIF). RIF potentiated additional 4,5-linked AGs, such as neomycin and ribostamycin, but not the clinically important 4,6-linked AGs amikacin and gentamicin. Potentiation was absent in a mutant lacking the AmgRS envelope stress response two-component system (TCS), which protects the organism from AG-generated membrane-damaging aberrant polypeptides and, thus, promotes AG resistance, an indication that RIF was acting via this TCS in potentiating 4,5-linked AG activity. Potentiation was also absent in a RIF-resistant RNA polymerase mutant, consistent with its potentiation of AG activity being dependent on RNA polymerase perturbation. PAR-inducible expression of the AmgRS-dependent genes htpX and yccA was reduced by RIF, suggesting that AG activation of this TCS was compromised by this agent. Still, RIF did not compromise the membrane-protective activity of AmgRS, an indication that it impacted some other function of this TCS. RIF potentiated the activities of 4,5-linked AGs against several AG-resistant clinical isolates, in two cases also potentiating the activity of the 4,6-linked AGs. These cases were, in one instance, explained by an observed AmgRS-dependent expression of the MexXY multidrug efflux system, which accommodates a range of AGs, with RIF targeting of AmgRS undermining mexXY expression and its promotion of resistance to 4,5- and 4,6-linked AGs. Given this link between AmgRS, MexXY expression, and pan-AG resistance in P. aeruginosa, RIF might be a useful adjuvant in the AG treatment of P. aeruginosa infections.

Topics: Amikacin; Anti-Bacterial Agents; Bacterial Proteins; Drug Resistance, Multiple, Bacterial; Drug Synergism; Gene Expression Regulation, Bacterial; Gentamicins; Heat-Shock Proteins; Humans; Membrane Proteins; Microbial Sensitivity Tests; Paromomycin; Pseudomonas aeruginosa; Pseudomonas Infections; Ribostamycin; Rifampin; Stress, Physiological

Multidrug-resistant Pseudomonas aeruginosa has emerged as one of the most important healthcare-associated pathogens. Colistin is regarded as the last-resort antibiotic for multidrug-resistant Gram-negative bacteria, but is associated with high rates of acute kidney injury. The aim of this in vitro study is to search for an alternative treatment to colistin for multidrug-resistant P. aeruginosa infections.. Multidrug and carbapenem-resistant P. aeruginosa isolates were collected between January 2009 and December 2012 at MacKay Memorial Hospital. Minimal inhibitory concentrations (MICs) were determined for various antibiotic combinations. Carbapenemase-producing genes including bla VIM, other β-lactamase genes and porin mutations were screened by PCR and sequencing. The efficacy of carbapenems (imipenem, meropenem, doripenem) with or without rifampicin was correlated with the type of porin mutation (frameshift mutation, premature stop codon mutation) in multidrug-resistant P. aeruginosa isolates without carbapenemase-producing genes.. Of the 71 multidrug-resistant clinical P. aeruginosa isolates, only six harboured the bla VIM gene. Imipenem, meropenem and doripenem were significantly more effective (reduced fold-change of MICs) when combined with rifampicin in bla VIM-negative isolates, especially in isolates with porin frameshift mutation.. Imipenem + rifampicin combination has a low MIC against multidrug-resistant P. aeruginosa, especially in isolates with porin frameshift mutation. The imipenem + rifampicin combination may provide an alternative treatment to colistin for multidrug -resistant P. aeruginosa infections, especially for patients with renal insufficiency.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Colistin; Doripenem; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Meropenem; Microbial Sensitivity Tests; Middle Aged; Porins; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Taiwan; Thienamycins

Colistin has been increasingly used for the treatment of respiratory infections caused by Gram-negative bacteria. Unfortunately parenteral administration of colistin can cause severe adverse effects. This study aimed to develop an inhaled combination dry powder formulation of colistin and rifapentine for the treatment of respiratory infections. The combination formulation was produced by spray-drying rifapentine particles suspended in an aqueous colistin solution. The combination dry powder had enhanced antimicrobial activities against planktonic cells and biofilm cultures of Pseudomonas aeruginosa, with both minimum inhibitory concentration (MIC) and minimum biofilm inhibitory concentration (MBIC) values (2 and 4 mg/L, respectively) being half that of pure colistin (MIC 4 mg/L and MBIC 8 mg/L) and 1/16th that of pure rifapentine (MIC 32 mg/L and MBIC 64 mg/L). High aerosol performance, as measured via an Aerolizer device, was observed with emitted doses>89% and fine particle fraction (FPF) total>76%. The proportion of submicron particles of rifapentine particles was minimized by the attachment of colistin, which increased the overall particle mass and aerodynamic size distribution. Using the spray-drying method described here, stable particles of amorphous colistin and crystalline rifapentine were distributed homogeneously in each stage of the impinger. Unlike the colistin alone formulation, no deterioration in aerosol performance was found for the combination powder when exposed to a high relative humidity of 75%. In our previous study, surface coating by rifampicin contributed to the moisture protection of colistin. Here, a novel approach with a new mechanism was proposed whereby moisture protection was attributed to the carrier effect of elongated crystalline rifapentine particles, which minimized contact between hygroscopic colistin particles. This inhaled combination antibiotic formulation with enhanced aerosol dispersion efficiency and in vitro efficacy could become a superior treatment for respiratory infections.

Topics: Administration, Inhalation; Anti-Infective Agents; Biofilms; Colistin; Drug Combinations; Drug Synergism; Dry Powder Inhalers; Humans; Microbial Sensitivity Tests; Nanoparticles; Nasal Sprays; Particle Size; Plankton; Powders; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections; Rifampin

Topics: Adult; Anti-Bacterial Agents; Carbapenems; Colistin; Doripenem; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Humans; Male; Meningoencephalitis; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Surgical Wound Infection; Treatment Outcome

Persisters are specialized survivor cells that protect bacterial populations from killing by antibiotics. Persisters are dormant phenotypic variants of regular cells rather than mutants. Bactericidal antibiotics kill by corrupting their targets into producing toxic products; tolerance to antibiotics follows when targets are inactive. Transcriptome analysis of isolated persisters points to toxin/antitoxin modules as a principle component of persister formation. Mechanisms of persister formation are redundant, making it difficult to eradicate these cells. In Escherichia coli, toxins RelE and MazF cause dormancy by degrading mRNA; HipA inhibits translation by phosphorylating Ef-Tu; and TisB forms an anion channel in the membrane, leading to a decrease in pmf and ATP levels. Prolonged treatment of chronic infections with antibiotics selects for hip mutants that produce more persister cells. Eradication of tolerant persisters is a serious challenge. Some of the existing antibiotics are capable of killing persisters, pointing to ways of developing therapeutics to treat chronic infections. Mitomycin is a prodrug which is converted into a reactive compound forming adducts with DNA upon entering the cell. Prolonged treatment with aminoglycosides that cause mistranslation leading to misfolded peptides can sterilize a stationary culture of Pseudomonas aeruginosa, a pathogen responsible for chronic, highly tolerant infections of cystic fibrosis patients. Finally, one of the best bactericidal agents is rifampin, an inhibitor of RNA polymerase, and we suggest that it "kills" by preventing persister resuscitation.

Topics: Anti-Bacterial Agents; Biofilms; Biological Products; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Microbial Viability; Mycobacterium tuberculosis; Ofloxacin; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Species Specificity; Time Factors; Tuberculosis

Extreme drug-resistant Pseudomonas aeruginosa (XDR-PA) with decreased susceptibility to polymyxin B (PB) has emerged in Singapore, causing infections in immunocompromised hosts. Combination therapy may be the only viable therapeutic option until new antibiotics become available. The objective of this study is to assess the in vitro activity of various antibiotics against local XDR-PA isolates.. PA isolates from all public hospitals in Singapore were systematically collected between 2006 and 2007. MICs were determined according to CLSI guidelines. All XDR-PA isolates identified were genotyped using a PCR-based method. Time-kill studies (TKS) were performed with approximately 10(5) CFU/ml at baseline using clinically achievable unbound concentrations of amikacin (A), levofloxacin (L), meropenem (M), rifampicin (R) and PB alone and in combination. Bactericidal activity (primary endpoint) was defined as a ≥3 log(10) CFU/ml decrease in the colony count from the initial inoculum at 24 hours.. 22 clinical XDR-PA isolates with PB MIC 2-16 µg/ml were collected. From clonal typing, 5 clonal groups were identified and nine isolates exhibited clonal diversity. In TKS, meropenem plus PB, amikacin plus meropenem, amikacin plus rifampicin, amikacin plus PB exhibited bactericidal activity in 8/22, 3/22, 1/22 and 6/22 isolates at 24 hours respectively. Against the remaining ten isolates where none of the dual-drug combination achieved bactericidal activity against, only the triple-antibiotic combinations of ARP and AMP achieved bactericidal activity against 7/10 and 6/10 isolates respectively.. Bactericidal activity with sustained killing effect of ≥99.9% is critical for eradicating XDR-PA infections, especially in immunocompromised hosts. These findings underscore the difficulty of developing combination therapeutic options against XDR-PA, demonstrating that at least 3 antibiotics are required in combination and that efficacy is strain dependant.

Topics: Amikacin; Anti-Bacterial Agents; beta-Lactamases; Drug Resistance, Bacterial; Drug Synergism; Drug Therapy, Combination; Humans; Levofloxacin; Meropenem; Microbial Sensitivity Tests; Ofloxacin; Phylogeny; Polymyxin B; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Thienamycins; Time Factors

In vitro double and triple bactericidal activities of doripenem, polymyxin B, and rifampin were assessed against 20 carbapenem-resistant clinical isolates with different mechanisms of carbapenem resistance. Bactericidal activity was achieved in 90% of all bacteria assayed using combinations of polymyxin B, doripenem, and rifampin against five each of the carbapenem-resistant Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli isolates studied. Combinations with these antibacterials may provide a strategy for treatment of patients infected with such organisms.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Doripenem; Drug Combinations; Drug Resistance, Multiple, Bacterial; Escherichia coli; Escherichia coli Infections; Humans; In Vitro Techniques; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Polymyxin B; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin

The in vitro activities of 10 families of antimicrobial agents alone and in combination with a synthetic polycationic polymer, polyethylenimine (PEI), against a resistant clinical isolate of Pseudomonas aeruginosa were investigated by MIC assays, checkerboard testing, and killing curve studies. At a concentration of 250 nM, PEI (10 kDa) was not directly bactericidal or bacteriostatic; but when it was used in combination with novobiocin, ceftazidime, ampicillin, ticarcillin, carbenicillin, piperacillin, cefotaxime, chloramphenicol, rifampin, or norfloxacin, it significantly reduced the MICs of these antibiotics by 1.5- to 56-fold. However, the MICs of aminoglycosides, polymyxins, and vancomycins were increased by 1.2- to 5-fold when these drugs were combined with PEI; and the MICs of tetracycline, erythromycin, ciprofloxacin, and ofloxacin were not affected when these drugs were combined with PEI. In the killing curve studies, combinations of PEI with novobiocin, ceftazidime, chloramphenicol, or rifampin resulted in 5- to 8-log(10) CFU/ml reductions in bacterial counts when 25% of the MIC of each antibiotic was used. These results indicate that infections due to resistant Pseudomonas strains could be treated by the use of a synergistic combination of PEI and antimicrobial drugs.

Topics: Aminoglycosides; Anti-Bacterial Agents; Carbenicillin; Ceftazidime; Ciprofloxacin; Drug Resistance, Bacterial; Drug Synergism; Humans; Microbial Sensitivity Tests; Novobiocin; Ofloxacin; Piperacillin; Polyethyleneimine; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Ticarcillin; Tobramycin

New arr alleles emerged in class 1 integrons from a clinical Pseudomonas aeruginosa strain (arr-4) and four Klebsiella pneumoniae strains (arr-5) in Brazil/American continent. arr-4 was preceded by aacA7-catB3, whereas arr-5 was the unique cassette. The putative proteins shared 75% (Arr-5) and 78% (Arr-4) identities with Arr-2.

Topics: Alleles; Amino Acid Sequence; Base Sequence; Brazil; DNA, Bacterial; Humans; Integrons; Klebsiella Infections; Klebsiella pneumoniae; Molecular Sequence Data; Pseudomonas aeruginosa; Pseudomonas Infections; Sequence Analysis, DNA; Sequence Homology, Amino Acid

An experimental study has been performed to compare the in vitro activity and the in vivo efficacy of magainin II and cecropin A with or without rifampicin against control and multidrug-resistant Pseudomonas aeruginosa strains.. In vitro experiments included MIC determinations and synergy studies. For in vivo studies, animals were given an intraperitoneal injection of P. aeruginosa lipopolysaccharide, P. aeruginosa ATCC 27853 and one clinical multiresistant P. aeruginosa strain. Groups of animals received intravenously isotonic sodium chloride solution, 10 mg/kg rifampicin, 1 mg/kg magainin II or 1 mg/kg cecropin A. Two groups of animals received a combined treatment with magainin II + rifampicin or cecropin A + rifampicin at the same dosages as the singly treated groups. In addition, a further group was treated with tazobactam/piperacillin (120 mg/kg). Lethality, bacterial growth in blood and peritoneum, and endotoxin and TNF-alpha concentrations in plasma were evaluated.. Combinations of alpha-helical antimicrobial peptides showed in vitro synergistic interaction. Magainin II and cecropin A exerted strong antimicrobial activity and achieved a significant reduction in plasma endotoxin and TNF-alpha concentrations when compared with control and rifampicin-treated groups. Rifampicin exhibited no anti-P. aeruginosa activity and good substantial impact on endotoxin and TNF-alpha plasma concentrations. Combined treatment groups had significant reductions in bacterial count, positive blood cultures and mortality rates when compared with singly treated and control groups.. Our results highlight the potential usefulness of these combinations that provide future therapeutic alternatives in P. aeruginosa infections.

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Blood; Drug Synergism; Drug Therapy, Combination; Endotoxins; Injections, Intravenous; Magainins; Microbial Sensitivity Tests; Penicillanic Acid; Peritoneum; Piperacillin; Piperacillin, Tazobactam Drug Combination; Plasma; Pseudomonas aeruginosa; Pseudomonas Infections; Rats; Rats, Wistar; Rifampin; Survival Analysis; Treatment Outcome; Tumor Necrosis Factor-alpha; Xenopus Proteins

To investigate the efficacy of rifampin and colistin in three experimental rat models of Pseudomonas aeruginosa sepsis.. Prospective, randomized, controlled animal study.. Research laboratory in a university hospital.. Adult male Wistar rats.. Adult male Wistar rats were given a) an intraperitoneal injection of 1 mg of P. aeruginosa 10 lipopolysaccharide; b) 2 x 10(10) colony-forming units of P. aeruginosa ATCC 27853; and c) 2 x 10(10) colony-forming units of one clinically multiresistant strain of P. aeruginosa. For each model, all animals were randomized to receive intravenously isotonic sodium chloride solution, 10 mg/kg rifampin, 1 mg/kg colistin, and 10 mg/kg rifampin plus 1 mg/kg colistin.. Lethality, bacterial growth in blood and peritoneum, and endotoxin and tumor necrosis factor-alpha concentrations in plasma were measured. Colistin exerted a strong antimicrobial activity and achieved a significant reduction of plasma endotoxin and tumor necrosis factor-alpha concentration compared with control and rifampin-treated groups. Rifampin exhibited no antimicrobial activity with no substantial impact on endotoxin and tumor necrosis factor-alpha plasma concentrations. The combination of colistin and rifampin resulted in a significant reduction in bacterial count compared with colistin monotherapy, whereas no significant difference was found in positive hem cultures and mortality rates between the two groups.. Colistin and rifampin might have a role in the therapy of multiresistant P. aeruginosa infection.

Topics: Animals; Anti-Bacterial Agents; Cells, Cultured; Colistin; Colony Count, Microbial; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Male; Microbial Sensitivity Tests; Prospective Studies; Pseudomonas Infections; Random Allocation; Rats; Rats, Wistar; Rifampin; Shock, Septic; Survival Analysis

Topics: Animals; Anti-Bacterial Agents; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Gram-Negative Bacterial Infections; Humans; Pseudomonas Infections; Rats; Rifampin; Sepsis; Treatment Failure

Topics: Adult; Anti-Bacterial Agents; Cellulitis; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Neutropenia; Phlebitis; Polymyxin B; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Treatment Outcome

A patient with an ulcerated cutaneous leishmaniasis of the pinna had suppurative otochondritis after a first unsuccessful course of treatment with meglumine antimoniate. Although the Leishmania ulceration healed after a second course of meglumine antimoniate, and despite three oral dicloxacillin or pristinamycin courses, the otochondritis extended and an abscess developed. Pus from the abscess revealed a pure culture of Pseudomonas aeruginosa. Five days of oral ciprofloxacin plus rifampin led to a marked improvement. The P. aeruginosa isolate was sensitive to ciprofloxacin but fully resistant to rifampin. Healing with minimal mutilation was obtained at the end of a six-week course of multiple antibiotic therapy. Pseudomonas aeruginosa otochondritis was a co-factor of cartilage mutilation in this patient. Thus, infection with P. aeruginosa should be promptly treated when present in tender cutaneous or mucosal leishmaniasis lesions near cartilaginous areas.

Topics: Adult; Animals; Anti-Infective Agents; Antimony; Antiprotozoal Agents; Cartilage; Ciprofloxacin; Ear, External; Humans; Immunocompetence; Leishmaniasis, Cutaneous; Male; Meglumine; Meglumine Antimoniate; Organometallic Compounds; Pseudomonas Infections; Rifampin

The evaluation of the safety and effectiveness of colistin in association with rifampin and imipenem in 1 diabetic patient with severe diabetic foot infection (DFI) due to multidrug-resistant (MDR) Pseudomonas aeruginosa, complicated by osteomyelitis, is presented in this "Case Report". The patient received colistin after other ineffective antimicrobial treatment when an MDR P aeruginosa strain was isolated by cultural examination, together with a multidisciplinary care approach including surgical debridement and adequate offloading. The efficacy of combination colistin plus rifampin plus imipenem was observed with a checkerboard method and bactericidal activity of the serum. The patient received colistin combination therapy for 6 weeks with cure of the infection and without renal toxicity. These data suggest that colistin, in combination with rifampin and imipenem, is safe and effective, in promoting healing in DFI due to MDR P aeruginosa and suggest the need for controlled clinical studies.

Topics: Aged; Anti-Bacterial Agents; Colistin; Diabetic Foot; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Follow-Up Studies; Humans; Imipenem; Male; Metatarsal Bones; Osteomyelitis; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin

The aim of the study was to assess the microbiological activity and clinical efficacy of colistin and rifampin combination against multidrug-resistant (MDR) Pseudomonas aeruginosa infections. The antimicrobial activity of the colistin/rifampin combination was evaluated using the checkerboard and time-kill curve methods against different MDR P. aeruginosa strains. The combination of rifampin and colistin resulted fully (1 strain) or partially (5 strains) synergistic for 6/7 strains and minimum inhibitory concentrations (MICs) in combination were reduced to easily obtainable therapeutic levels. The time-kill curves showed that the combination was bactericidal against the strains tested. The clinical efficacy of the combination was tested in four patients with difficult-to treat infections (sepsis or pneumonia) caused by MDR P. aeruginosa. All infections were successfully treated. Our microbiological and clinical observations suggest that the addition of rifampin to colistin may result in a synergistic bactericidal combination that may be useful in patients with infections caused by MDR P. aeruginosa which are difficult to cure.

Topics: Adult; Colistin; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Female; Humans; Italy; Male; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Sampling Studies; Sensitivity and Specificity; Treatment Outcome

To investigate most common pathogens isolated from the hospital-acquired pneumonia patients bronchoalveolar lavage fluid in Kaunas University of Medicine Hospital according to the previous antibiotic use and to estimate pathogens antibacterial susceptibility.. Results of 87 hospital-acquired pneumonia patients bronchoalveolar lavage fluid quantitative cultures were analyzed. Microorganisms isolated in clinically significant amount were considered as the etiological agents and included into analysis. Susceptibility was tested using the standard methods. Previously untreated patients were considered if the antibacterials were not administered at all or were used less than for 24 hours.. H. influenzae isolation in significant amount rates were higher in previously untreated patients group comparing to previously treated (29.2%. (n=14) and 5.1% (n=2), respectively, p<0.05). Non-fermenters (P. aeruginosa and Acinetobacter spp.) isolation rates were higher in those previously treated comparing to untreated patients - (31.0% (n=13) and 4.2% (n=2), respectively, p<0.05). All H. influenzae strains were susceptible to ampicillin and cefuroxime. 22.2-44.4% of P. aeruginosa strains were resistant to ceftazidime, amikacin and ciprofloxacin. Estimated Acinetobacter spp. resistance to ciprofloxacin and gentamycin was 83.3% and to ampicillin/sulbactam - 16.7%. All methicillin-susceptible S.aureus were also susceptible to gentamycin and fucidin and methicillin resistant to rifampicin and vancomycin.. Previous antibiotic treatment has an impact on pneumonia etiology testing. H. influenzae strains are more common isolated hospital-acquired pneumonia etiologic agents in previously untreated patients. The low antibacterial resistance was found enabling the use of aminopenicillins for treatment if H. influenzae infection suggested. The use of antibacterials increases non-fermenters isolation rates and combined antipseudomonal treatment is reasonable in these patients.

Topics: Acinetobacter; Acinetobacter Infections; Amikacin; Ampicillin; Anti-Bacterial Agents; Anti-Infective Agents; Bacteria; Bronchoalveolar Lavage Fluid; Ceftazidime; Cefuroxime; Ciprofloxacin; Cross Infection; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Fusidic Acid; Gentamicins; Haemophilus Infections; Haemophilus influenzae; Humans; Male; Methicillin; Microbial Sensitivity Tests; Middle Aged; Penicillins; Pneumonia, Bacterial; Pneumonia, Staphylococcal; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Staphylococcus aureus; Sulbactam; Vancomycin Resistance

A clinical isolate of Pseudomonas aeruginosa was found to produce a clavulanic acid-inhibited extended-spectrum beta-lactamase with a pI of 6.4. PCR, cloning, and sequencing experiments showed that the corresponding bla(TEM-21) gene was part of a chromosomally located Tn801 transposon disrupted by an IS6100 element and adjacent to an aac(3)-II gene.

Topics: Aged; Antibiotics, Antitubercular; Azides; beta-Lactamases; Chromosomes, Bacterial; Conjugation, Genetic; DNA, Bacterial; Drug Resistance, Bacterial; Escherichia coli; Female; Humans; Molecular Sequence Data; Pseudomonas aeruginosa; Pseudomonas Infections; Reverse Transcriptase Polymerase Chain Reaction; Rifampin

Prosthetic valve endocarditis (PVE) is a relatively uncommon but very serious condition. As bacterial colonization of the prosthetic heart valve sewing cuff can be a prelude to the clinical occurrence of PVE, antimicrobial coating of the sewing cuff may be beneficial. The study aims were to examine the antimicrobial activity in vitro and anti-infective efficacy in vivo of prosthetic heart valve sewing cuffs coated with minocycline and rifampin.. Zones of inhibition by antimicrobial-coated sewing cuffs were assessed in vitro against Staphylococcus epidermidis, S. aureus, Enterococcus faecalis, Pseudomonas aeruginosa and Candida albicans. The ability of subcutaneously implanted devices coated with minocycline and rifampin to resist colonization and infection by P. aeruginosa was also examined in a rabbit model.. Antimicrobial-coated sewing cuffs produced zones of inhibition against all tested organisms. Coated devices were significantly less likely than uncoated devices to become colonized (2/24; 8% versus 20/24; 83%; p <0.001) or to cause device-related infection (0/24; 0% versus 18/24; 75%; p <0.001) and device-related abscess (0/24; 0% versus 10/24; 42%; p <0.001) due to P. aeruginosa.. Prosthetic heart valve sewing cuffs coated with minocycline and rifampin provide broad-spectrum antimicrobial activity in vitro, and are anti-infective in vivo against P. aeruginosa. These results encourage the clinical evaluation of these sewing cuffs.

Topics: Animals; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antibiotics, Antitubercular; Coated Materials, Biocompatible; Drug Therapy, Combination; Heart Valve Prosthesis; In Vitro Techniques; Minocycline; Prosthesis Design; Prosthesis-Related Infections; Pseudomonas Infections; Rabbits; Rifampin

The interest of the management of bone infections in the diabetic foot, inspired by the recommendations for the treatment of chronic osteitis, was assessed in this study.. Twenty bone infections in 17 diabetic patients with moderate to mild infections of the feet were confirmed by the results of X-ray and/or scintigraphic studies and bone surgery biopsy cultures revealing one or more bacteria sensitive to standard osteitis treatment (rifampicine + fluoroquinolone). The patients had received this treatment per os for a median duration of 6 months (3 to 10 months). Clinical follow-up was carried out during a consultation at 1, 3 and 6 months during treatment and then by telephone every six months after the end of treatment. Clinical success was defined as the disappearance of any local sign of infection and by the absence of relapse during the post-treatment follow-up period. The evolution of the bone infection was also assessed by the results of a control conducted 3 to 6 months after initiation of the antibiotic treatment.. At the end of the treatment, all signs of infection had disappeared in 15/17 patients (88.2%) and no relapse had occurred in 14 (82.3%) patients at the end of a median post-treatment period of 22 months (12 to 41 months). Resection of necrotic bone was performed at the same time as the bone biopsy in 2 patients. The median duration of hospitalisation was of 14 days (3 to 53 days). During the study, a multi-resistant germ was isolated in 4 patients (1 Pseudomonas aeruginosa, 3 Staphylococcus aureus). During the post-treatment follow-up, 3 patients dies from causes unrelated to the infection treated. No serious adverse event was reported during the study.. The results of this pilot study support the rationale of applying the treatment regimens of chronic osteitis to diabetic lesions of the feet, but are only applicable to comparable patients presenting with non-severe lesions of the feet. Moreover, the use of antibiotics with potent selection of resistance such as rifampicine and fluoroquinolone, requires that bone biopsies be taken, which is not easy in all the diabetic foot care centres. We are presently conducting a study to identify the sub-populations of diabetic patients who could benefit from such treatment.

Topics: Aged; Anti-Infective Agents; Antibiotics, Antitubercular; Biopsy; Chronic Disease; Diabetic Foot; Drug Resistance, Multiple; Female; Fluoroquinolones; Humans; Male; Middle Aged; Osteitis; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

Topics: Amikacin; Anti-Bacterial Agents; Antibiotics, Antitubercular; Colistin; Drug Resistance, Multiple; Drug Therapy, Combination; Humans; Microbial Sensitivity Tests; Middle Aged; Pseudomonas Infections; Rifampin

In continuous flow biofilm cultures in medium resembling cystic fibrosis bronchial secretions, Pseudomonas aeruginosa was not eradicated from biofilms by 1 week of treatment with high concentrations of ceftazidime and gentamicin, to which the strains were sensitive on conventional testing. The addition of rifampicin, which has little activity against the strains as measured by the minimum inhibitory concentration, led to the apparent elimination of the bacteria from the biofilms. The effect was not strain specific.

Topics: Anti-Bacterial Agents; Biofilms; Bronchi; Ceftazidime; Cephalosporins; Cystic Fibrosis; Drug Synergism; Drug Therapy, Combination; Gentamicins; Humans; Polysaccharides, Bacterial; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections; Rifampin; Time Factors

Topics: Animals; Biofilms; Blood Vessel Prosthesis; Combined Modality Therapy; Dogs; Humans; Models, Biological; Polyethylene Terephthalates; Prosthesis-Related Infections; Pseudomonas Infections; Reoperation; Rifampin; Staphylococcal Infections; Staphylococcus epidermidis

Topics: Administration, Oral; Adolescent; Alkaline Phosphatase; Child; Ciprofloxacin; Cystic Fibrosis; Drug Resistance, Microbial; Female; Follow-Up Studies; Humans; Joint Diseases; Lung Diseases; Male; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Safety

Shunt infections in children have become a serious problem. In order to solve this, we have been using antibiotic therapy with Rifampicin (Rifampin) for the last 2 years; the dosage is 20 mg/kg per day 1 h before surgery and then for 48 h after the surgical procedure. We have had experience with 203 children operated on between January 1987 and December 1988. The result was a significant decrease in the number of children with shunt infections. In 1980 we reported an incidence of 10%, while by 1988 the rate had gone down to 1%.

Topics: Dose-Response Relationship, Drug; Drug Administration Schedule; Equipment Contamination; Escherichia coli Infections; Follow-Up Studies; Humans; Hydrocephalus; Infant; Infant, Newborn; Infection Control; Klebsiella Infections; Postoperative Complications; Premedication; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Staphylococcal Infections; Surgical Wound Infection; Ventriculoperitoneal Shunt

Treatment of disseminated Pseudomonas aeruginosa infection in leukopenic mice was evaluated using cefpirome alone and in combination with gentamicin and/or rifampin. Mice were made leukopenic with cyclophosphamide and infected through a skin incision with an inoculum of 1250 organisms (13 LD50). Antibiotics were administered subcutaneously for 48 h. Although the addition of cefpirome to gentamicin and/or rifampin improved survival significantly at 48 h compared with untreated controls (84.6%-100% vs. 38.5%), therapy with these combinations did not improve survival significantly from that achieved with cefpirome alone. Quantitative blood and tissue (liver, spleen, kidney, lung) cultures in mice treated with cefpirome alone or including rifampin were lower than in infected controls or groups receiving therapy that excluded cefpirome. Highest counts were observed in mice receiving cefpirome plus gentamicin. Except for the cefpirome plus gentamicin group, which demonstrated areas of acute tubular necrosis, the cefpirome group had less tissue pathology than infected controls.

Topics: Animals; Cefpirome; Cephalosporins; Drug Therapy, Combination; Gentamicins; Kidney; Leukopenia; Liver; Lung; Male; Mice; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Spleen

Malignant external otitis is an invasive pseudomonal infection characteristically afflicting the elderly patient with diabetes mellitus. Therapy has traditionally consisted of the long-term administration of combination parenteral antibiotics, but morbidity and mortality remain substantial despite this therapy. We treated 11 consecutive patients with the oral combination of ciprofloxacin (750 mg twice daily) and rifampin (600 mg twice daily) for 6 to 12 weeks (mean, 8 weeks). Pseudomonas aeruginosa was isolated from ear canal or mastoid, and bone destruction was documented by computed tomography in all patients. Seven patients (64%) had ear irrigation before onset of the infection. Ten patients fulfilled the criteria of both clinical and bacteriologic cure. No serious adverse reaction to either antibiotic was observed. Otalgia and otorrhea responded at a mean of 6 and 4 days, respectively, following the initiation of therapy. The erythrocyte sedimentation rate fell from a mean pretherapy value of 81 mm/h (range, 41 to 138 mm/h) to 18 mm/h (range, 3 to 45 mm/h) after the completion of antibiotic therapy. Minimum inhibitory and bactericidal concentrations established that all organisms were sensitive to ciprofloxacin. Time-kill curve and checkerboard assays failed to demonstrate either synergy or antagonism between ciprofloxacin and rifampin. Serum inhibitory and bactericidal titers showed minimal increase in inhibition and killing of the bacteria with the addition of rifampin. Rifampin did not alter the pharmacokinetics of ciprofloxacin. The successful use of oral antibiotics for this difficult infection may be a major advance. Reduction in antibiotic costs and hospitalization and convenience of oral administration were of notable benefit.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Blood Sedimentation; Ciprofloxacin; Diabetes Complications; Drug Synergism; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Otitis Externa; Pseudomonas aeruginosa; Pseudomonas Infections; Recurrence; Rifampin

Topics: Animals; Male; Parotid Gland; Pseudomonas Infections; Rats; Rats, Inbred Strains; Rifampin

Experimental intraabdominal abscesses were produced in mice by intraperitoneal injection of Bacteroides fragilis and Pseudomonas aeruginosa. The therapeutic efficacy of rifampicin and cefsulodin alone, and in combination was investigated in this in-vivo experimental mixed intraabdominal abscess model. Treatment with rifampicin at 10, and 25 mg/kg or cefsulodin at 50, and 100 mg/kg singly or in combinations prevented mortality as compared to 68% mortality rate occurring in the untreated mice. Rifampicin, at 25 mg/kg dose, was very effective in preventing abscess formation and produced bacterial eradication. It prevented abscess formation in 80% of the mice and eradicated both Bacteroides and Pseudomonas in 100% and 75% of the abscesses of the mice. Cefsulodin failed to reduce the incidence of abscess formation, and to eradicate Bact. fragilis from the abscesses, although it significantly decreased Ps. aeruginosa in the abscesses. The combination of rifampicin at 10 mg/kg and cefsulodin at 100 mg/kg was more effective than either of the antibiotics alone and was as effective as rifampicin alone at 25 mg/kg levels. This combination was bactericidal against both organisms in the infected mice.

Topics: Abscess; Animals; Bacteroides fragilis; Bacteroides Infections; Cefsulodin; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Mice; Peritoneal Diseases; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin

The efficacy of ticarcillin (100 mg/kg), tobramycin (1 mg/kg), and rifampin (43 and 7.2 mg/kg) individually and in combination was assessed in neutropenic mice infected with an LD90 of one of four Pseudomonas aeruginosa isolates. The study end point was survival at 120 hours after infection. Treatment with the triple combination, ticarcillin plus tobramycin plus rifampin (43 mg/kg), was significantly superior to the double combination of ticarcillin plus tobramycin (p less than 0.01). Although treatment with rifampin (43 mg/kg) alone yielded results similar to treatment with the triple combination in mice infected with three of the four isolates, rifampin-resistant mutants (minimal inhibitory concentration greater than 1000 micrograms/ml) of P. aeruginosa were frequently isolated from surviving mice (26% of mice sampled). In contrast, in mice treated with the triple combination, rarely were rifampin-resistant mutants isolated (3% of mice sampled). Rifampin alone was active against P. aeruginosa isolates only when peak serum concentrations of rifampin exceeded the rifampin minimal bactericidal concentration of the infecting isolate. The addition of rifampin to a "standard" therapy of antipseudomonal penicillin plus aminoglycoside may be useful in the treatment of serious P. aeruginosa infection.

Topics: Animals; Cyclophosphamide; Drug Evaluation, Preclinical; Drug Therapy, Combination; Endotoxins; Exotoxins; Female; Mice; Microbial Sensitivity Tests; Neutropenia; Penicillin Resistance; Penicillins; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin; Ticarcillin; Tobramycin

Four patients infected with Pseudomonas aeruginosa were treated with the triple therapy of carboxypenicillin (carbenicillin or ticarcillin), aminoglycoside (gentamicin or tobramycin), and rifampin. Two patients had P. aeruginosa endocarditis, one had bacteremia associated with granulocytopenia, and one had neurosurgical meningitis. In all four cases, the clinical condition of the patient deteriorated on combined antipseudomonal penicillin and aminoglycoside therapy. All patients had persistent blood cultures (throughout a 3- to 30-day period) or cerebrospinal fluid cultures (throughout a 24-day period) while receiving penicillin-aminoglycoside therapy. Rifampin, 600 mg every 8 h orally, was added to the penicillin-aminoglycoside regimen. All four patients defervesced within 24 h after the initiation of rifampin. In addition, all four patients experienced sterilization of blood and cerebrospinal fluid cultures within 24 h of therapy. The emergence of rifampin-resistant P. aeruginosa was not observed. Ultimately, two patients survived their infection; the other two patients succumbed to complications of their underlying disease. This clinical experience should provide a stimulus for a controlled evaluation of rifampin as a component of multiple drug therapy directed against P. aeruginosa.

Topics: Adult; Anti-Bacterial Agents; Carbenicillin; Drug Therapy, Combination; Gentamicins; Humans; Male; Pseudomonas Infections; Rifampin; Ticarcillin; Tobramycin

The survival level of the experimental animals with infection caused by Staphylococcus and Ps. aeruginosa was the highest when the animals were treated with a combination of gentamicin and rifampicin as compared to the use of every antibiotic alone. The combination had a more favourable effect on the plasmocytic reaction and production of the antibody-forming cells in the lymphoid organs which correlated with the therapeutic efficacy of the antibiotics.

Topics: Animals; Antibody-Producing Cells; Drug Evaluation, Preclinical; Drug Therapy, Combination; Gentamicins; Mice; Plasma Cells; Pseudomonas Infections; Rifampin; Staphylococcal Infections; Time Factors

During the period 1965-79 191 cystic fibrosis patients have been treated with 2349 course of anti-staphylococcal chemotherapy in the Danish Cystic Fibrosis Centre. The standard treatment was orally administered Fusidic acid in combination with Oxacillin or Dicloxacillin given for 14 days. In cases of penicillin allergy Fusidic acid in combination with Rifampicin was given. The overall results showed that S. aureus was eradicated from sputum by a single course of chemotherapy in 74% of the cases, although in 8% the original strains (phage-type) was replaced by a new strain. Repeated or extended treatment was successful in most of the remaining cases and, as a result, only 9% of our patients harboured S. aureus continuously for 6 months or more. On the average each patient received 2 anti-staphylococcal treatment per year, but no decrease in efficacy of repeated treatment was seen. Likewise, no significant increase of S. aureus precipitins and no development of resistant strains was seen in our patients. Due to the efficacy of chemotherapy and the principles of early treatment whether there are clinical symptoms of infection or not, S. aureus infection is now considered a minor problem without relation to poor prognosis in our cystic fibrosis patients.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Child; Child, Preschool; Cystic Fibrosis; Dicloxacillin; Female; Fusidic Acid; Humans; Infant; Male; Oxacillin; Probenecid; Pseudomonas Infections; Rifampin; Staphylococcal Infections

Topics: Adult; Aortic Valve; Colistin; Drug Therapy, Combination; Endocarditis, Bacterial; Heart Valve Prosthesis; Humans; Male; Postoperative Complications; Pseudomonas Infections; Rifampin; Tobramycin

Studies on the chemotherapeutic action of rifampicin in treatment of staphylococcal sepsis and sepsis caused by gramnegative organisms showed its high efficacy only in treatment of the staphylococcal infection. By the level of its efficacy rifampicin was much superior to benzylpenicillin and especially tetracycline. No difference in the activity level of the antibiotic in treatment of staphylococcal infections caused by sensitive and multiple resistant staphylococcal strains was found. In treatment of the infections caused by gramnegative organisms the drug activity was moderate.

Topics: Acute Disease; Animals; Bacterial Infections; Chronic Disease; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Escherichia coli Infections; Mice; Moscow; Proteus Infections; Pseudomonas Infections; Rifampin; Staphylococcal Infections

Two and half years after a circling buckle operation in which two Supra-mid sutures and a solid silicone explant were employed, a Pseudomonas infection developed around the explant and progressed to the inner eye. Removal of all implanted foreign material and treatment with Rifamicin saved the eye. The relevant literature on infection following sclero-plastic procedures is reviewed, and the pathogenesis of the late infections is discussed.

Topics: Female; Humans; Middle Aged; Pseudomonas Infections; Rifampin; Rifamycins; Scleral Buckling; Surgical Wound Infection; Sutures

Topics: Animals; Conjunctiva; Diarrhea; Dimethyl Sulfoxide; Edetic Acid; Gentamicins; Keratitis; Male; Microbial Sensitivity Tests; Pseudomonas Infections; Rabbits; Rifampin; Solubility

Topics: Anti-Bacterial Agents; Bacterial Infections; Carbenicillin; Cephalexin; Cephaloglycin; Cephalosporins; Enterobacteriaceae Infections; Gentamicins; Humans; Pseudomonas Infections; Rifampin; Staphylococcal Infections

Topics: Acute Disease; Adult; Chronic Disease; Escherichia coli Infections; Female; Humans; Male; Middle Aged; Proteus Infections; Pseudomonas Infections; Rifampin; Staphylococcal Infections; Urinary Tract Infections; Urologic Diseases

Topics: Bronchial Diseases; Chloramphenicol; Humans; Lung Diseases; Microbial Sensitivity Tests; Pseudomonas Infections; Rifampin; Staphylococcal Infections; Streptococcal Infections; Tetracycline

Topics: Animals; Anti-Bacterial Agents; Drug Resistance, Microbial; Evaluation Studies as Topic; Mice; Pseudomonas; Pseudomonas Infections; Rifampin

Topics: Anti-Bacterial Agents; Drug Synergism; Gentamicins; Humans; Microbial Sensitivity Tests; Oxytetracycline; Penicillins; Pseudomonas; Pseudomonas Infections; Rifampin

Topics: Animals; Anti-Bacterial Agents; Chloramphenicol; Drug Resistance, Microbial; Melioidosis; Mice; Pseudomonas; Pseudomonas Infections; Rifampin; Tetracycline