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PubMed1997

Ventricular shunt infection and meningitis due to Bacillus cereus.

Non-anthrax Bacillus species are usually considered to be contaminants if found in clinical specimens. Only a few patients with systemic infections due to Bacillus cereus are reported. We present the case of a 18-month old boy with a primitive neuroectodermal tumor (PNET) in the brainstem and obstructive hydrocephalus that required an outlying and subsequently a ventriculoperitoneal drain. Following contamination at the site of entry of the external drain, shunt infection and meningitis with Bacillus cereus developed. Antibiotic treatment with vancomycin failed to eliminate the bacterium from the cerebrospinal fluid, so the shunt system had to be removed. Explantation of the shunt and addition of fosfomycin to the antibiotic regimen resulted in a complete cure of the infection.

Bacillaceae Infections↗
PubMed1994

[Presacral phlegmons and meningitis as the complications of a foreign body in the rectosigmoid].

A 24-year-old patient presented with severe back pain in the lumbar and sacral regions and septic temperatures up to 40 degrees C. Lasègue's sign was bilaterally positive. An enhanced cell count was seen in the CSF (1877 cells/microliters, erythrocytes 1024/microliters). Total protein concentration was 4440 mg/dl. The patient also suffered from granulocytic pleocytosis. X-ray as well as scintigrams revealed inflammation of the presacral soft parts involving the os sacrum and bone marrow. Treatment with doxycycline (200 mg/d), fosfomycin (5 g/d), netilmicin (400 mg/d) and ofloxacin (200 mg/d) succeeded in curing the meningitis, whereas the presacral phlegmon persisted. Endoscopic examination showed a rod-shaped foreign body in the rectum that had penetrated deeply into the mucosa and required deformation and removal by laser. The plastic rod of 10 cm length was probably a liquorice stick. The patient denied introducing it per anum; he suspected having swallowed it while drunk. The inflammation subsided rapidly after removal of the foreign body.

Adult↗
PubMed2003

Urinary tract infection: traditional pharmacologic therapies.

Urinary tract infections (UTIs) are common bacterial infections, particularly in women. Antimicrobial therapy is seldom indicated for asymptomatic infection, but antimicrobial therapy is usually indicated for amelioration of symptoms. Management of acute uncomplicated UTI (cystitis) is generally straightforward, with a predictable distribution of uropathogens isolated. First-line treatment of acute uncomplicated UTI has traditionally involved a 3-day regimen of trimethoprim-sulfamethoxazole (TMP-SMX) or TMP alone for patients with sulfa allergies. Increasing resistance among community-acquired Escherichia coli to TMP-SMX worldwide has led to a reassessment of the most appropriate empiric therapy for these infections. Alternative first-line agents include the fluoroquinolones, nitrofurantoin, and fosfomycin. Factors to be considered in the selection of appropriate antimicrobial therapy include pharmacokinetics, spectrum of activity of the antimicrobial agent, resistance prevalence for the community, potential for adverse effects, and duration of therapy. Ideal antimicrobial agents for UTI management have primary excretion routes through the urinary tract to achieve high urinary drug levels. In addition, there are special considerations in the management of UTI among selected populations, including postmenopausal and pregnant women, and for women with frequent recurrent UTIs.

Adolescent↗
PubMed2002

The murMN operon: a functional link between antibiotic resistance and antibiotic tolerance in Streptococcuspneumoniae.

Inactivation of the recently identified murMN operon in penicillin-resistant strains of Streptococcus pneumoniae was shown already to cause two major effects: elimination of branched-structured muropeptides from the cell wall and complete loss of penicillin resistance. We now show that cells with inactivated murMN also have a third phenotype: an increased susceptibility to lysis when exposed to low concentrations of fosfomycin, d-cycloserine, vancomycin, and nisin, indicating a wide-spectrum hypersensitivity to inhibitors of both early and late stages of cell wall biosynthesis. Mutants of murMN also lysed faster than the parental strain when treated with the detergent deoxycholate. Several different alleles of murM cloned in plasmid pLS578 and introduced into a murM deletion mutant of the penicillin-resistant strain Pen6 were able to reconstitute each one of the three mutant phenotypes: the highly branched cell wall structure, original high level of penicillin resistance, and normal sensitivity to lysis. In a penicillin-susceptible strain the same experiments caused increased concentration of cell wall branched peptides and suppression of sensitivity to antibiotic induced lysis. The observations suggest that the murMN operon plays a key role in the regulation of a stress-response pathway that can be triggered by perturbation of cell wall biosynthesis in S. pneumoniae.

Alleles↗
PubMed2002

Microbiological evaluation of a commercial transport system for urine samples.

The aim of this study was to evaluate a commercial tube prepared with boric acid, sodium formate and sorbitol (Hemogard Vacutainer tubes, Becton-Dickinson, HG tubes). Fourteen bacterial strains were incubated in urine in HG tubes and conventional tubes. During a 24-h period, most of the microorganisms grew readily in conventional tubes at room temperature, whereas the bacterial counts were comparatively unchanged when chilled or kept in HG tubes. The bacterial counts of Alcaligenes faecalis and lactobacilli decreased by two 10 logarithms in the HG tubes, at room temperature. Experiments were also performed with the addition of various antibiotics. Ciprofloxacin caused a decrease in E. coli counts regardless of type of tube used, while the HG tubes and the conventional tubes kept chilled conserved bacterial counts upon challenge with fosfomycin, trimethoprim or mecillinam. Bedside cultures from 154 outpatients were sampled and divided into three tubes. One conventional tube was sent to our laboratory by ordinary chilled transport. Another conventional tube and one HG tube were transported to the laboratory without chilling. Cultures were performed upon arrival at the laboratory and then 24, 48 and 72 h after primary sampling. Within 24 h of sampling, no significant differences in bacterial counts were observed between chilled conventional tubes and the HG tubes at room temperature. However, in the HG tubes a significant change in enterococcal counts was noted within 48 h.

Anti-Bacterial Agents↗
PubMed2003

Postoperative spondylodiskitis due to Stomatococcus mucilaginosus in an immunocompetent patient.

A case is reported of postoperative spondylodiskitis due to Stomatococcus mucilaginosus in an immunocompetent woman. The route of infection remains unknown. Intravenous treatment with cefotaxime and fosfomycin was given, followed by oral administration of rifampin and pristinamycin until resolution of infection. This report shows that this bacterium can cause severe infections in immunocompetent patients.

Adult↗
PubMed2004

Modulation of the human interleukin-12p40 response by a triazole antifungal derivative, itraconazole.

Some types of antimicrobial agents such as fosfomycin, clarithromycin, and erythromycin have been known to affect the host's immunological response. We investigated whether itraconazole (ITCZ) can modulate the serum cytokine levels (tumor necrosis factor (TNF-alpha, interleukin (IL)-10, IL-12p40) in both patients and healthy subjects. Serum samples were collected and TNF-alpha, IL-10 and IL-12p40 were measured using a sandwich enzyme-linked immunosorbent assay (ELISA). We showed increased levels of IL-12p40 in patients treated with ITCZ. In healthy subjects, moreover, ITCZ treatment significantly increased the production of IL-12p40, but not TNF-alpha or IL-10. These findings suggest that the effectiveness of ITCZ in the treatment of fungal infection may be due not only to its direct antifungal effect, but also to induction of an immunomodulative effect on the host defense systems by regulation of cytokine production.

Adult↗
PubMed2001

The role of murMN operon in penicillin resistance and antibiotic tolerance of Streptococcus pneumoniae.

The recently identified murMN operon is essential for the production of branched-structured muropeptides in the cell wall and also for the expression of the resistant phenotype in penicillin-resistant strains of Streptococcus pneumoniae. The purpose of studies described in this communication was to understand better the role of murMN in penicillin resistance. Deletion of murM in the penicillin-resistant strain Pen6, which causes reduction in the penicillin MIC from 6.0 to 0.03 microg/ml, was successfully complemented to recover the original high level of penicillin resistance in transformants that received functional murM alleles cloned in plasmid pLS578. Inactivation of penicillin resistance was not accompanied by any detectable change in the low affinity or abnormal molecular size pattern of the penicillin-binding proteins (PBPs) nor in the mosaic sequence of PBP2X typical of resistant strain Pen6. Exposure of strain Pen6 with inactivated murM to 0.05 microg/ml of penicillin (i.e., a concentration more than 100 times below the MIC of the parental strain) initiated a phenotypic response typical of penicillin-susceptible strains of pneumococci: inhibition of growth followed by rapid and extensive loss of viability and lysis. Unexpectedly, inactivation of murMN also caused hypersensitivity to lysis by low concentrations of a variety of cell wall active antibiotics such as fosfomycin, D-cycloserine, and nisin, suggesting that the murMN operon may perform an important regulatory role in the control of the irreversible antimicrobial effects of cell wall inhibitors.

Alleles↗
PubMed2003

Normally functioning murF is essential for the optimal expression of methicillin resistance in Staphylococcus aureus.

A carboxy-terminal fragment of murF was used to construct and insert a suicide plasmid into the chromosomal copy of the gene in the highly and homogeneously methicillin-resistant Staphylococcus aureus (MRSA) strain COL by Campbell type integration. The plasmid insertion generated a mutant in which the MIC value for oxacillin was reduced from 400 microg/ml of the parental strain to 0.75 microg/ml in 90% of the cells of the mutant cultures that were heterogeneous: they contained subpopulations of bacteria with a frequency of 10(-3) that were capable of expressing resistance at nearly the parental level. The impact of the murF mutation on antibiotic resistance was selective for beta-lactam antibiotics: there was no change in the susceptibility of the mutant to D-cycloserine, fosfomycin, beta-D-chloro-alanine, moenomycin, bacitracin, or vancomycin. Analysis of the mutant peptidoglycan showed decrease in the percentage of oligomeric components in rough proportion to the accumulation of several abnormal muropeptide components, which were identified as structural variants of the disaccharide tripeptide monomer. An abnormal cell wall precursor identified as UDP MurNac tripeptide was also detected in the cytoplasmic pool of the mutant strain. A normal proportion of oligomers and a greatly reduced representation of the disaccharide tripeptide were demonstrated in the cell wall of the murF mutant's subpopulation that has retained the parental level of resistance. Northern analysis demonstrated a drastic reduction in the transcription rate of mecA in mutant F9 whereas mecA transcription increased in the subpopulation of bacteria that retained high-level resistance.

Amino Acid Sequence↗
PubMed2004

Identification of a variant "Rome clone" of methicillin-resistant Staphylococcus aureus with decreased susceptibility to vancomycin, responsible for an outbreak in an intensive care unit.

We describe the identification of a variant of the "Rome clone" of methicillin-resistant Staphylococcus aureus (MRSA), responsible for an outbreak involving 5 patients in a Cardiac Surgery Intensive Care Unit (CS-ICU) of a tertiary-care University Hospital in Rome. All strains isolated from patients and from nasal swabs obtained from four members of the CS-ICU personnel, belonged to the same identified clone. The characteristics of this clone were: (1) resistance to ampicillin, oxacillin, gentamicin, ciprofloxacin, erythromycin, clindamycin, rifampin, spectinomycin, and tetracycline; (2) vancomycin and teicoplanin MICs respectively of 2 and 4 mg/L; (3) heteroresistant subpopulations in the presence of 4 and 6 mg/L of vancomycin (10(-3) and 10(-5), respectively); (4) clonal type I::J::C determined following an established protocol (mec A::Tn 554 ::PFGE); (5) sequence type ST247 (3-3-1-12-4-4-16), obtained by multilocus sequence typing (MLST); and (6) the staphylococcal cassette chromosome mec (SCC) IA, obtained by multiplex PCR method. This new strain had different characteristics from the epidemic clone circulating in the same hospital from 1997 and designed "Rome clone," which was susceptible to erythromycin, clindamycin, and spectinomycin and belonged to the II::NH::C genetic background. A high genetic similarity between this Rome clone and the previously classified Archaic and Iberian clones was found, because they shared the same allelic profile (ST247), probably originating from the same S. aureus ancestor of the Iberian MRSA strains. Therefore, the strains responsible for the outbreak, with vancomycin MICs 2-4 mg/L, are variant clones, showing the genotype of the "Rome clone," the ST247 in association with SCC mec type IA (ST247-MRSA-IA), and are characterized by a uniform susceptibility to fosfomycin.

Anti-Bacterial Agents↗
PubMed1998

Spread of the multiresistant Iberian clone of methicillin-resistant Staphylococcus aureus (MRSA) to Italy and Scotland.

The multidrug-resistant "Iberian" clone of methicillin-resistant Staphylococcus aureus (MRSA) was first identified on the basis of its unique DNA fingerprints as the strain responsible for the massive 1989 outbreak of MRSA disease in the hospital Princeps d'Espanya, Barcelona, Spain. Most Iberian MRSA carry a constitutive beta-lactamase. They are resistant to most beta-lactam antibiotics, macrolides, aminoglycosides, tetracycline, rifampin and ciprofloxacin and are susceptible to fosfomycin, fusidic acid, mupirocin, sulfamethoxazole/trimethoprim and vancomycin. The characteristic DNA fingerprints of the clone include the mecA polymorph I, Tn554 pattern E (or its variants), a chromosomal macrorestriction pattern (pulsed-field gel electrophoretic type) A (or its subtype variants), the lack of the mecI regulatory gene and a homogeneous, high level of expression of methicillin resistance. Molecular surveillance studies have documented the extensive spread of this clone to many Portuguese hospitals during the 1990s. In this article, we describe the spread of the Iberian MRSA to hospitals in Rome, Italy, and Scotland.

Anti-Bacterial Agents↗
PubMed1998

Spread of a methicillin-resistant and multiresistant epidemic clone of Staphylococcus aureus in Argentina.

One hundred forty-eight recent methicillin-resistant Staphylococcus aureus (MRSA) isolates collected from 13 hospitals in Argentina were examined for antibiotic susceptibility and clonal type, using hybridization with DNA probes specific for mecA and Tn554, and pulsed-field gel electrophoresis (PFGE) of chromosomal SmaI digests. The majority of the isolates (62.2%) shared the common PFGE B pattern and carried variants of mecA and Tn554 polymorphs characteristic of an MRSA clone widely spread in Brazilian hospitals. Similarly to the Brazilian isolates, the MRSA clone recovered in the Argentinian hospitals (XI::B::B) and its close relatives (XI::B'::B, XI::AA::B, XI::M::B, XI::omega omega::B, and III::W::B) showed susceptibility to spectinomycin and resistance to numerous antibacterial agents, including beta-lactams, tetracycline, aminoglycosides, macrolides, trimethoprim/sulfamethoxazole, ciprofloxacin, and fosfomycin, and more than 60% of the isolates were also resistant to chloramphenicol and rifampin. The XI::B::B MRSA clone represented the majority of isolates recovered in most of the hospitals, nine of which were located in the city of Buenos Aires, three in the province of Buenos Aires, and one in the province of Tucumán, 1,312 km northwest of the city of Buenos Aires. The observations document further geographic expansion of this South American MRSA clone across national boundaries.

Anti-Bacterial Agents↗
PubMedDate not supplied

Synergy of fluoroquinolones with other antimicrobial agents.

Synergy resulting from the combination of ciprofloxacin and an antipseudomonal penicillin has been reported for 20%-50% of isolates of Pseudomonas aeruginosa. A similar effect has also been reported for the combination of ciprofloxacin and fosfomycin. In contrast, the combination of quinolones and aminoglycosides rarely showed synergy when tested against P. aeruginosa. Most studies have shown that the combination of beta-lactams or aminoglycosides with quinolones is indifferent against Escherichia coli, Klebsiella species, Enterobacter species, Citrobacter species, and Serratia species. The combination of ciprofloxacin and chloramphenicol can be antagonistic against E. coli. In general, the combination of quinolone antibiotics with other drugs tested against staphylococci, enterococci, and anaerobic species has shown indifference. The neutropenic mouse model of infection has demonstrated the synergistic effect of ciprofloxacin plus antipseudomonal penicillins; the combination of ciprofloxacin and rifampin has been superior to single agents in experimental Staphylococcus aureus osteomyelitis. Ciprofloxacin has been the quinolone studied most thoroughly, and few data are available about the combination of other quinolones with other antimicrobial agents. Overall, the occurrence of synergy when quinolones are combined with other antimicrobial agents is infrequent, and clinical studies that demonstrate the clinical relevance of data from in vitro and animal models of infection are not available. However, data from in vitro and animal model studies indicate that the combination of a quinolone with other antimicrobial agents rarely results in antagonism.

4-Quinolones↗
PubMed1987

Teicoplanin: renal tolerance and pharmacokinetics in rats.

The nephrotoxicity and pharmacokinetics of teicoplanin were studied in an experimental rat model. Nephrotoxicity was assessed by measuring urinary excretion of tubular cells and malate dehydrogenase. The experiments revealed that 1 mg/kg or more of teicoplanin daily resulted in an increase of excretion rates of tubular cells. Similarly to vancomycin, teicoplanin is accumulated in the kidneys. Nephrotoxicity induced by teicoplanin can be reduced by coadministration of fosfomycin and D-glucaro-1.5-lactam, and enhanced by administration of tobramycin. We conclude that renal function should be monitored closely during teicoplanin therapy.

Animals↗
PubMed1990

Experimental studies on nephrotoxicity and pharmacokinetics of LY 146032 (daptomycin) in rats.

The nephrotoxicity and pharmacokinetics of LY 146032 (daptomycin) were studied in an experimental rat model. Nephrotoxicity was assessed by measuring urinary loss of tubular cells and malate dehydrogenase. LY 146032 (10-250 mg/kg daily iv) led to a dose-dependent and reversible increase of cell elimination. The tubulo-toxic threshold dose is stated to be 10 mg/kg daily. Nephrotoxicity induced by LY 146032 can be reduced by coadministration of fosfomycin or D-glucaro-1.5-lactam, and enhanced by combination with tobramycin. LY 146032 accumulated in renal tissue during repeated administration. Electron microscopy revealed histopathological changes in the kidneys. Therefore the nephrotoxic potential of LY 146032 should be taken into consideration in clinical trials.

Animals↗
PubMed1991

Effect of combination therapy with recombinant human granulocyte colony-stimulating factor (rG-CSF) and antibiotics in neutropenic mice unresponsive to antibiotics alone.

The effect of recombinant human granulocyte colony-stimulating factor (rG-CSF) in enhancing antimicrobial chemotherapy was investigated. Combined treatments of rG-CSF with cefotaxime, cefazolin, fosfomycin, gentamicin or amphotericin B were evaluated in systemic infections with Pseudomonas aeruginosa, Escherichia coli, Serratia marcescens, Staphylococcus aureus and Candida albicans in leucopenic mice induced by pretreatment with cyclophosphamide. Administration of appropriate antibiotics afforded a dose-related inhibition of death from infection in normal mice and mice treated with rG-CSF after cyclophosphamide injection. In cyclophosphamide-treated mice, even larger doses of the antibiotics failed to provide protection against infection with the same inoculum size. These results suggest the possibility that rG-CSF could be of help in treatments with antimicrobial agents against infections in leucopenic patients.

Animals↗
PubMed1993

Experimental endocarditis: a review of its relevance to human endocarditis.

Bacterial endocarditis is a difficult-to-cure infection, owing to (i) poor penetration of antibiotics into infected vegetations; (ii) altered metabolic state of bacteria within the lesion; (iii) absence of adequate host-defence cellular response which could cooperate with antibiotic action. The contribution of infection models to definition and improvement of therapeutic regimens of endocarditis in man remains of great importance because of the difficulties encountered in clinical trials. The advantage of the experimental model is that besides the fact that it closely simulates the characteristics of the infection in humans, it provides clear endpoints which allow statistical comparisons among different therapeutic regimens: number of bacteria/g of tissue, frequency of emergence of resistance, positivity of blood cultures, death vs survival rates, and percentage of relapses after treatment has been stopped. All these parameters are more sensitive and more easy to use than in man. The infection model has definitively established that bactericidal therapy is warranted and that in-vitro susceptibility tests, especially those evaluating the killing rate, have a good predictive value for the therapeutic outcome. Three main aspects are discussed for their influence on human therapy (i) the kinetics of antibiotic diffusion into vegetations, with a special reference to the data obtained by autoradiography, (ii) the specificity of some pharmacodynamic aspects of antibiotics in endocarditis, including the clinical consequences of these two parameters on antibiotic dosing regimens and length of therapy, and (iii) in-vivo synergy. This phenomenon involves a variety of mechanisms which are difficult or even impossible to analyse on the sole basis of in-vitro data: enhanced bactericidal activity (beta-lactam-aminoglycoside), prevention of emergence of resistance (as demonstrated for rifampin, quinolones or fosfomycin) and, as shown with rifampin or quinolones, 'pharmacokinetic synergy'. Animal models have helped to define the importance of antibiotic dosing strategies to achieve in-vivo synergy which appears as essential to increase the rate of both bacteriological and clinical cure rate.

Animals↗
PubMed1994

Effect of combination of oxacillin and non-beta-lactam antibiotics on methicillin-resistant Staphylococcus aureus.

The in-vitro activity of oxacillin combined with non-beta-lactam antibiotics, bacitracin, vancomycin, enduracidin, tunicamycin, flavomycin, fosfomycin, and cycloserine, was investigated in 23 methicillin-resistant and 15 methicillin-susceptible Staphylococcus aureus strains. In the presence of a non-beta-lactam antibiotic (0.25 MIC), the MICs of oxacillin for methicillin-resistant S. aureus (MRSA) strains and methicillin-susceptible S. aureus (MSSA) strains were lowered. This effect was most marked with MRSA strains, and bacitracin, flavomycin, and tunicamycin increased the susceptibility of MRSA to oxacillin by greater than 200-fold. More than 87% and 77% of MRSA and MSSA strains, respectively, were synergically inhibited by a combination of oxacillin with bacitracin, tunicamycin, flavomycin or cycloserine (fractional inhibitory concentration < or = 0.5). Polyanetholesulfonic acid prevented the lysis of MRSA cells treated with a combination of oxacillin and 0.25 MIC of bacitracin, but did not prevent cell death. The penicillin binding protein (PBP) profile of MRSA was not affected by incubation with 0.25 MIC of non-beta-lactam antibiotics. These results suggest that the increased antibacterial activity of oxacillin in the presence of non-beta-lactam antibiotic is not the consequence of activation of autolysis or of a decrease in bulk PBP synthesis.

Anti-Bacterial Agents↗