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PubMed1988

Protective effect of piperacillin against nephrotoxicity of cephaloridine and gentamicin in animals.

The protective effect of piperacillin against the nephrotoxicity of cephaloridine and gentamicin was examined in experimental animals. In rabbits, piperacillin was infused at a dose of 1 mg/kg (body weight) per min over 225 min and cephaloridine (300 mg/kg) was intravenously administered as a bolus 45 min after the start of a drip infusion. Blood urea nitrogen, serum creatinine, and N-acetyl-beta-D-glucosaminidase (NAG) in urine were measured as the renal toxicological parameters before and 24 h after cephaloridine dosing. Although the single administration of cephaloridine significantly elevated these parameters, the elevation was prevented by the concomitant administration of piperacillin. The protective effect of piperacillin was superior to those of cephalothin and fosfomycin. In rats, piperacillin (1,000 mg/kg) was intravenously administered and immediately followed by the intramuscular administration of gentamicin (100 mg/kg) every 24 h for 5 days. When piperacillin was concomitantly administered with gentamicin, the elevations of blood urea nitrogen, serum creatinine, and urinary NAG were significantly lower than when gentamicin was given alone. The concomitant administration of piperacillin resulted in a significant protective effect against the nephrotoxicity of cephaloridine in rabbits and of gentamicin in rats. Histopathological observation also supported the protective effect of piperacillin. The protective mechanism of piperacillin might be the inhibition of transport from the peritubular side to tubular cells for cephaloridine and from both the peritubular and luminal sides for gentamicin.

Animals↗
PubMed1996

Modulatory effect of antibiotics on cytokine production by human monocytes in vitro.

Some antimicrobial agents have been reported to modify the host immune and inflammatory responses both in vivo and in vitro. Fosfomycin (FOM) and clarithromycin (CAM) have immunomodulatory activity on human lymphocyte function. In the present study, we examined the effects of FOM and CAM on cytokine synthesis by lipopolysaccharide (LPS)-stimulated human monocytes in comparison with that of dexamethasone in vitro. The three drugs demonstrated positive or negative effects on the synthesis of various cytokines by LPS-primed monocytes. They suppressed the synthesis of tumor necrosis factor alpha, interleukin 1 alpha (IL-1 alpha), IL-1 beta, the IL-1 receptor antagonist, and granulocyte-macrophage colony-stimulating factor in a concentration-dependent manner at concentrations between 1.6 and 40 micrograms/ml. On the contrary, the drugs showed different actions on the synthesis of IL-6 and IL-10. Namely, FOM enhanced both IL-6 and IL-10 synthesis, CAM enhanced only IL-10 synthesis, but dexamethasone deeply suppressed the synthesis of both cytokines. These data indicate that antibacterial agents may modify acute-phase inflammatory responses through their effects on cytokine synthesis by monocytes.

Anti-Bacterial Agents↗
PubMed1976

Isolation and characterization of conjugation-deficient mutants of Escherichia coli K-12.

Conjugation-deficient mutants (Con-) of Escherichia coli K-12 have been isolated by a variety of indirect selective techniques. Mutants with mutations conferring ampicillin resistance, fosfomycin resistance, an alanine requirement, and a failure of ferment a number of carbohydrates were selected because the impaired functions occur in association with cell wall and cell membrane defects. The integrity of these catalytic or structural elements is postulated to have a role in conjugation. The mutants could be divided into at least six general categories corresponding to their defectiveness in the following postulated recipient cell functions: (i) specific-union formation, (ii) effective-union formation, (iii) deoxyribonucleic acid transfer, (iv) plasmid establishment, (v) plasmid maintenance, and (vi) recombination. The availability of these mutants should contribute to the description of the molecular events involved in each of these conjugation steps and the elucidation of these genetic control over the inheritance of conjugationally transferred deoxyribonucleic acid.

Alanine↗
PubMed1996

A vancomycin-inducible lacZ reporter system in Bacillus subtilis: induction by antibiotics that inhibit cell wall synthesis and by lysozyme.

We have constructed a Bacillus subtilis strain in which expression of a vanH::lacZ gene fusion is regulated by VanR and VanS of Enterococcus faecium. This construct allows a nonpathogenic bacterial strain to be used as a model system for studying regulation of vancomycin resistance. Antibiotics and enzymes that affect cell wall biosynthesis and stability were tested for the ability to induce lacZ expression. As a result, fosfomycin and D-cycloserine were added to the group of peptidoglycan synthesis inhibitors shown to induce expression from the vanH promoter. Induction by cell wall hydrolytic enzymes, as well as by antibiotics whose actions may lead to the accumulation of chemically different peptidoglycan precursors, raises the possibility that models that postulate induction by peptidoglycan [correction of peptidodoglycan] precursors are wrong.

Anti-Bacterial Agents↗
PubMed2003

Escherichia coli O157:H7 Shiga toxin-encoding bacteriophages: integrations, excisions, truncations, and evolutionary implications.

As it descended from Escherichia coli O55:H7, Shiga toxin (Stx)-producing E. coli (STEC) O157:H7 is believed to have acquired, in sequence, a bacteriophage encoding Stx2 and another encoding Stx1. Between these events, sorbitol-fermenting E. coli O157:H(-) presumably diverged from this clade. We employed PCR and sequence analyses to investigate sites of bacteriophage integration into the chromosome, using evolutionarily informative STEC to trace the sequence of acquisition of elements encoding Stx. Contrary to expectations from the two currently sequenced strains, truncated bacteriophages occupy yehV in almost all E. coli O157:H7 strains that lack stx(1) (stx(1)-negative strains). Two truncated variants were determined to contain either GTT or TGACTGTT sequence, in lieu of 20,214 or 18,895 bp, respectively, of the bacteriophage central region. A single-nucleotide polymorphism in the latter variant suggests that recombination in that element extended beyond the inserted octamer. An stx(2) bacteriophage usually occupies wrbA in stx(1)(+)/stx(2)(+) E. coli O157:H7, but wrbA is unexpectedly unoccupied in most stx(1)-negative/stx(2)(+) E. coli O157:H7 strains, the presumed progenitors of stx(1)(+)/stx(2)(+) E. coli O157:H7. Trimethoprim-sulfamethoxazole promotes the excision of all, and ciprofloxacin and fosfomycin significantly promote the excision of a subset of complete and truncated stx bacteriophages from the E. coli O157:H7 strains tested; bile salts usually attenuate excision. These data demonstrate the unexpected diversity of the chromosomal architecture of E. coli O157:H7 (with novel truncated bacteriophages and multiple stx(2) bacteriophage insertion sites), suggest that stx(1) acquisition might be a multistep process, and compel the consideration of multiple exogenous factors, including antibiotics and bile, when chromosome stability is examined.

Anti-Bacterial Agents↗
PubMed2006

Detailed genomic analysis of the Wbeta and gamma phages infecting Bacillus anthracis: implications for evolution of environmental fitness and antibiotic resistance.

Phage-mediated lysis has been an essential laboratory tool for rapidly identifying Bacillus anthracis for more than 40 years, relying on the gamma phage derivative of a Bacillus cereus prophage called W. The complete genomic sequences of the temperate W phage, referred to as Wbeta, and its lytic variant gamma were determined and found to encode 53 open reading frames each, spanning 40,864 bp and 37,373 bp, respectively. Direct comparison of the genomes showed that gamma evolved through mutations at key loci controlling host recognition, lysogenic growth, and possibly host phenotypic modification. Included are a cluster of point mutations at the gp14 tail fiber locus of gamma, encoding a protein that, when fused to green fluorescent protein, binds specifically to B. anthracis. A large 2,003-bp deletion was also identified at the gamma lysogeny module, explaining its shift from a temperate to a lytic lifestyle. Finally, evidence of recombination was observed at a dicistronic Wbeta locus, encoding putative bacterial cell surface-modifying proteins, replaced in gamma with a locus, likely obtained from a B. anthracis prophage, encoding demonstrable fosfomycin resistance. Reverse transcriptase PCR analysis confirmed strong induction at the dicistronic Wbeta locus and at four other phage loci in B. anthracis and/or B. cereus lysogens. In all, this study represents the first genomic and functional description of two historically important phages and is part of a broader investigation into contributions of phage to the B. anthracis life cycle. Initial findings suggest that lysogeny of B. anthracis promotes ecological adaptation, rather than virulence, as with other gram-positive pathogens.

Amino Acid Sequence↗
PubMed2005

[Treatment of uncomplicated lower urinary tract infections].

Empirical antibiotic treatment of lower urinary tract infections should be based on the patient's clinical data and on local sensitivity data. Because of the increase in resistance among uropathogens, recommendations on the empirical treatment of urinary tract infections have been modified. Currently, the empirical use of co-trimoxazole, ampicillin, and first-generation cephalosporins and quinolones is not recommended. Fluoroquinolones have been demonstrated to be highly effective in comparative studies but, because of the increase in resistance, the type of patient who can benefit from these antimicrobial agents must be selected. Second- and third-generation cephalosporins still have high sensitivity rates, although the higher recurrence rates associated with their use and the emergence of extended-spectrum beta-lactamase-producing enterobacterial in the community should be taken into account. Amoxicillin-clavulanate is less effective in eradicating infections than quinolones. Fosfomycin-trometamol has resistance rates of below 2% and single-dose therapy has been demonstrated to be safe and effective. Nitrofurantoin is also currently active, although it must be administered for 7 days and can produce toxicity. Both agents are currently recommended as alternative therapeutic options to fluoroquinolones in uncomplicated infections of the lower urinary tract.

Administration, Oral↗
PubMedDate not supplied

Susceptibility of Streptococcus mutans and Streptococcus sobrinus to cell wall inhibitors and development of a novel selective medium for S. sobrinus.

Representative strains of Streptococcus mutans and Streptococcus sobrinus showed differences in susceptibility to members of the monobactam group of beta-lactam antibiotics: S. sobrinus was less sensitive than S. mutans. The minimum inhibitory concentrations of aztreonam (AZT) and carumonam, both of which belong to this group, were 2,000 microg/ml for S. sobrinus and 125 microg/ml for S. mutans. Further addition of fosfomycin, bacitracin and sodium chloride to Mitis Salivarius agar (MS) supplemented with AZT resulted in growth inhibition of S. mutans and oral streptococci other than S. sobrinus, and was therefore used as a selective medium for S. sobrinus (MS-SOB medium). The average growth recovery of laboratory and clinically isolated strains of S. sobrinus on MS-SOB medium was 74.1% compared to that on MS medium. Seventy-eight percent of clinical samples in which S. sobrinus was detected yielded pure growth of S. sobrinus on MS-SOB medium.

Anti-Bacterial Agents↗
PubMed1986

Clostridium perfringens type A. Comparison of in vitro and in vivo activity of twelve antimicrobial drugs.

Penicillin G and imipenem (N-formimidoyl thienamycin) in vitro were the most active of twelve examined antimicrobial drugs against clinical and fecal isolates of Clostridium perfringens type A. However, vancomycin and fosfomycin, which revealed suboptimal in vitro bactericidal activity, proved as efficacious as penicillin G and imipenem in an experimental mode of murine gas gangrene. Thus, conventional in vitro tests were not uniformly predictive for in vivo (murine) chemotherapeutic efficacy.

Animals↗
PubMedDate not supplied

Enhanced susceptibility of Escherichia coli pretreated with RP7293 to leukocyte activity: comparison with other antimicrobial agents.

Antimicrobial agents may interact with polymorphonuclear leukocytes and directly modify the leukocyte functions, or bacteria can be modified by the antimicrobial agents causing them to be treated differently by phagocytic cells. Brief exposure of bacteria to high levels of antimicrobials can affect their interaction with leukocytes. The susceptibility of Escherichia coli to phagocytosis and killing by human polymorphonuclear leukocytes in the presence of normal human serum following treatment with RP7293, a new natural streptogramin, was examined, and a comparison made with clavulanic acid/amoxicillin, ciprofloxacin and fosfomycin. Pretreatment of E. coli for 10 min with 4 x MIC of RP7293 clearly sensitized the bacteria to leukocytic killing in the presence of normal human serum (10% v/v).

Amoxicillin↗
PubMed1987

Urinary tract infections in pregnancy: Monuril single-dose treatment versus traditional therapy.

Today, it is widely accepted that a short-course or single-dose treatment with antimicrobial agents in pregnancy is the optimal therapy to minimize the risk of toxicity both for the mother and the fetus. A randomized trial comparing single-dose (3 g) treatment with fosfomycin trometamol (FT) versus pipemidic acid (200-gram doses b.i.d. for 7 days) in bacteriuric pregnant women is presented. The preliminary results show that single-dose FT has the same cure effect as conventional therapy with pipemidic acid.

Bacteriuria↗
PubMedDate not supplied

Conventional and nonconventional modes of vancomycin administration to decontaminate the internal surface of catheters colonized with coagulase-negative staphylococci.

Using a quantitative in vitro model simulating clinical conditions, we studied the efficacy of conventional and nonconventional 3-day therapies involving vancomycin for treating the internal surface of catheters colonized with a slime-producing strain of Staphylococcus epidermidis. When infused for 1 hr every 8 hr through the catheter at the daily dose recommended for a 10-kg child (450 mg), vancomycin alone reduced bacterial colonization but failed to sterilize the inserts. Vancomycin was more active in combination with netilmicin (25 mg for 1 hr every 8 hr), rifampin (150 mg for 90 min every 12 hr), or fosfomycin (500 mg for 4 hr every 6 hr), but the catheters were inconsistently decontaminated after 3 days of treatment. Two nonconventional modes of antibiotic administration were tested for their capacity to ensure high levels of vancomycin in the catheter lumen over a prolonged time. Vancomycin infused continuously through the catheter at a daily dose of 450 mg had the same poor sterilizing effect as vancomycin administered intermittently. On the contrary, catheters were totally decontaminated when 2.5 mg of vancomycin in a volume of 0.5 ml were injected twice daily into noninfused catheters, confirming that the antibiotic-lock technique is an approach of great interest to sterilize the internal surface of catheters colonized with staphylococci.

Catheters, Indwelling↗
PubMed2000

Natural antibiotic susceptibility of Rahnella aquatilis and R. aquatilis-related strains.

A database is described of the natural susceptibilities of 70 Rahnella strains to 71 antibiotics. MIC values were determined by a microdilution procedure and evaluated by a table calculation program. Rahnella aquatilis and R. aquatilis-related strains were naturally resistant to amoxycillin, ticarcillin, fosfomycin and to antibiotics to which other species of Enterobacteriaceae are also intrinsically resistant, i.e. macrolides (except azithromycin), benzylpenicillin, oxacillin, rifampicin, fusidic acid, lincosamides and glycopeptides. Rahnella strains were also naturally resistant or intermediate to cefazolin, cefuroxime and loracarbef. All rahnellae were naturally sensitive or intermediate to doxycycline, minocycline, aminoglycosides, some penicillins and cephalosporins, carbapenems, aztreonam, quinolones, sulfamethoxazole, trimethoprim, cotrimoxazole, chloramphenicol and nitrofurantoin. Bimodal or broad MIC distributions were seen for several antibiotics, e.g. quinolones and cephalosporins. With the exception of quinolones no differences in natural antibiotic susceptibility were seen between reference strains of Rahnella genomovar 1 (n=6) and 2 (n=7). Reference strains of genomovar 1 were pyrase-positive and more susceptible to quinolones than reference strains of genomovar 2, which were pyrase-negative. By discrimination of all rahnellae in the pyrase-positive and pyrase-negative strains the MIC distributions for quinolones became smaller and unimodal. Under the conditions described pyrase might be a parameter to differentiate strains of Rahnella genomovars 1 and 2.

Amoxicillin↗
PubMed1996

[Nephrotoxicity and drug interaction of vancomycin (2)].

Vancomycin hydrochloride (VCM) has an antibacterial action against Gram positive bacteria, e.g., Methicillin-resistant Staphylococcus aureus (MRSA). In the clinical situation, there are patients with serious infections, being infected with not only MRSA, but also with Gram negative bacteria like Pseudomonas aeruginosa. Because VCM has the adverse reaction of nephrotoxicity, we are apprehensive about using VCM with other antibiotics, which might increase this problem. Therefore, the nephrotoxic effects and pharmacokinetics of VCM were examined in rabbits and compared with those in rabbits administered with VCM and other antibiotics. Responses indicating nephrotoxicity such as increases of serum creatinine concentration and BUN and morphological changes of the kidney were induced by the single injection of VCM at 300 mg/kg, i.v. In contrast, no abnormality of clinical data and morphological alteration were observed in the groups injected with VCM and imipenem (IPM)-cilastatin sodium (CS), flomoxef sodium (FMOX) or fosfomycin sodium (FOM). This was not true for groups injected with VCM and ceftazidime, cefpimizole sodium (CPIZ) or cefoperazone sodium. Clearance of VCM increased obviously in the groups injected with VCM and IPM-CS, FMOX or FOM, but decreased in those given VCM and CPIZ. Since the renal concentrations of VCM in the groups that were administered VCM with IPM-CS, FMOX or FOM were lower than that in the control group, IPM-CS, FMOX and FOM may decrease the nephrotoxicity of VCM by inhibiting its uptake into the kidney.

Animals↗
PubMed2021

Removal of peptidoglycan and inhibition of active cellular processes leads to daptomycin tolerance in Enterococcus faecalis.

Daptomycin is a cyclic lipopeptide antibiotic used in the clinic for treatment of severe enterococcal infections. Recent reports indicate that daptomycin targets active cellular processes, specifically, peptidoglycan biosynthesis. Within, we examined the efficacy of daptomycin against Enterococcus faecalis under a range of environmental growth conditions including inhibitors that target active cellular processes. Daptomycin was far less effective against cells in late stationary phase compared to cells in exponential phase, and this was independent of cellular ATP levels. Further, the addition of either the de novo protein synthesis inhibitor chloramphenicol or the fatty acid biosynthesis inhibitor cerulenin induced survival against daptomycin far better than controls. Alterations in metabolites associated with peptidoglycan synthesis correlated with protection against daptomycin. This was further supported as removal of peptidoglycan induced physiological daptomycin tolerance, a synergistic relation between daptomycin and fosfomycin, an inhibitor of the fist committed step peptidoglycan synthesis, was observed, as well as an additive effect when daptomycin was combined with ampicillin, which targets crosslinking of peptidoglycan strands. Removal of the peptidoglycan of Enterococcus faecium, Staphylococcus aureus, and Bacillus subtilis also resulted in significant protection against daptomycin in comparison to whole cells with intact cell walls. Based on these observations, we conclude that bacterial growth phase and metabolic activity, as well as the presence/absence of peptidoglycan are major contributors to the efficacy of daptomycin.

Anti-Bacterial Agents↗
PubMed1996

Therapeutic trials in 200 patients with HTLV-I-associated myelopathy/ tropical spastic paraparesis.

We report here the results of therapeutic trials in 200 patients with HTLV-I-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) conducted in our department between 1986 and 1993. Motor disability grades were improved by more than one grade in 69.5% (91/131) of patients by oral administration of prednisolone, 50% (3/6) by eperisone hydrochloride only, 43.8% (7/16) by blood purification (lymphocytapheresis and plasmapheresis), 40.0% (2/5) by intrathecal injection of hydrocortisone, 30.0% (3/10) by intravenous injection of high-dose methylprednisolone, 23.3% (10/43) by interferon-alpha (intramuscular injection and inhalation), 22.2% (2/9) by azathioprine, 20.0% (4/20) by high-dose vitamin C, 16.0% (4/25) by erythromycin, 12.5% (3/24) by salazosulfapyridine, 11.8% (2/17) by mizoribine, 7.1% (1/14) by fosfomycin, and 6.3% (1/16) by thyrotropin releasing hormone. No critical side effects of these therapies were seen with the exceptions of one patient with adult respiratory distress syndrome due to cytomegalovirus infection and one patient with drug-induced hepatitis/hepatic failure. Selection of these treatments for patients with HAM/ TSP must be considered on the basis of age, sex, disease severity and complications to reduce adverse events and to improve quality of life. Although the results were a synopsis of different treatments given to 200 patients with HAM/ TSP as an open trial, we consider this the first report of a large-scale therapeutic trial in patients with HAM/TSP. The results of this study indicate that immunomodulatory therapies have some beneficial effects in HAM/TSP, and the functions of these agents are related to the pathophysiology of this disease.

Administration, Oral↗
PubMed2003

Life-threatening infantile diarrhea from fluoroquinolone-resistant Salmonella enterica typhimurium with mutations in both gyrA and parC.

Salmonella Typhimurium DT12, isolated from a 35-day-old infant with diarrhea, was highly resistant to ampicillin, tetracycline, chloramphenicol, streptomycin, gentamycin, sulfamethoxazole/trimethoprim, nalidixic acid, and fluoroquinolones. The patient responded to antibiotic therapy with fosfomycin. Multidrug-resistance may become prevalent in Salmonella infections in Japan, as shown in this first case of a patient infected with fluoroquinolone-resistant Salmonella.

Anti-Infective Agents↗
PubMed1993

[Clinical observation of acute otitis media in children].

The efficacy of a combination of cefaclor and fosfomycin otic solution was investigated in 81 children with acute otitis media, who needed myringotomy for severe erythema and swelling of the tympanic membrane. The patients were followed up for one year to investigate correlations between test findings of early treatment and both clinical course and prognosis. These drugs were used for 10 days, and the effects of combined use were evaluated from findings in the tympanic membrane after the 10-day period. Three stages were assessed; cured, recovered and unchanged. In cured and recovered cases, the administration was evaluated to be effective. Within 2 weeks after the start of treatment, views of the ears, nose and epipharynx were roentgenographically examined for shadows of mastoid pneumatization and the paranasal sinuses, and the presence or absence of adenoid vegetation. After the antibiotic administration, the patients were instructed to visit us at least once every 3 months to rule out recurrence of acute otitis media and otitis media with effusion (possibly occurring one year after treatment). The following results were obtained. 1. The two drug combination was effective in 99% of patients, produced no side effects, and was deemed extremely useful. 2. The course of acute otitis media tended to be significantly prolonged in patients with mastoid pneumatization and paranasal sinus shadows as revealed by roentgenography.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗