Comparative Studies of Fluoroquinolones in the Treatment of Urinary Tract Infections

The results of comparative trials of fluoroquinolones for the treatment of uncomplicated and complicated urinary tract infections (UTI) were reviewed. Severalrandomized, comparative trials showedthat in uncomplicatedUTI norfloxacin, ciprofloxacin, and ofloxacin wereat least as effectiveas trimethoprim-sulfamethoxazole (TMP-SMZ) and amoxicillinand usually more effectivethan nalidixicacid, pipemidic acid, and nitrofurantoin. Comparativetrials of single-dose regimens have, however, beenlimited. A few randomized, comparative trials have shown that in complicated UTI norfloxacin, ciprofloxacin, and ofloxacin wereat least as effectiveas amoxicillinand TMP-SMZand usually more effective than pipemidic acid. Moreover, preliminary results indicate that fluoroquinolones might be effective for the oral treatment of complicated UTI that are difficult to treat, especially those due to Pseudomonas aeruginosa. Comparative trials are neededto establish the value of fluoroquinolones for chronic bacterial prostatitis. There are no conclusivedata on fluoroquinolone treatment of UTI in patients with renal failure. Emergence of resistantpathogensduring therapywith fluoroquinolones has beeninfrequentbut might be more frequent in complicated UTI caused by P. aeruginos

Failure of Dexamethasone to Prevent Polymorphonuclear Leukocyte Infiltration During Experimental Acute Exudative Pyelonephritis and to Reduce Subsequent Chronic Scarring

In experimental acute exudative pyelonephritis (AEP), a role for polymorphonuclear leukocyte (PMNL) infiltration in the pathogenesis of kidney scarring has been suggested indirectly. To directly quantitate PMNL infiltration during AEP, we developed an assay for measuring the content in the kidney of myeloperoxidase (MPO), an enzyme present in PMNLs and absent in kidney tissue. This assay was a specific and sensitive marker of the kidney PMNL content. We used this assay to measure in rats with AEP the effect of dexamethasone, administered in an attempt to mitigate the acute inflammatory response. Compared with saline, dexamethasone given during AEP strikingly reduced kidney swelling, measured by the kidney-weight increase, but failed to reduce PMNL infiltration, measured by the kidney MPO content. Despite reduced kidney swelling during AEP, dexamethasone treatment failed to prevent subsequent kidney scarring, an observation indicating that PMNLs playa role in the development of permanent kidney damage during AE

Single-Dose Rifampin Prophylaxis for Experimental Endocarditis Induced by High Bacterial Inocula of Viridans Streptococci

In rats challenged with viridans streptococci poorly susceptible to antibiotic killing, single doses of antibiotics only prevent endocarditis induced by bacterial inoculum sizes that produce disease in 90% of control animals (ID90) : additional doses are required to protect against inocula exceeding the ID90. We investigated whether single-dose rifampin would extend the efficacy of single-dose prophylaxis to inocula exceeding the ID90. We used two strains of viridans streptococci highly susceptible to killing by rifampin and two resistant strains. All rats wereinjected with 10-1,000 times the ID90 of the four strains. Single-dose rifampin successfully prevented endocarditis due to all four strains. A few prophylaxis failures were observed after challenge with the two poorly susceptible strains, but in vivo emergence of resistant variants did not account for these failures. Thus, rifampin was the first antibiotic given as a single dose that successfully prevented experimental streptococcus endocarditis after challenge with high bacterial inocul

Role of Complement-Derived and Bacterial Formylpeptide Chemotactic Factors in the In Vivo Migration of Neutrophils in Experimental Escherichia coli Pyelonephritis in Rats

In experimental Escherichia coli pyelonephritis, the bacterial multiplication in the kidney parenchyma triggers a burst of neutrophil extravascular migration, as measured by the myeloperoxidase (MPO) activity in the kidney, a marker for tissue neutrophil infiltration. To test the mechanisms of in vivo neutrophil migration, pyelonephritis was surgically induced in rats that were then either complement-depleted with cobra venom factor (CVF), resulting in a profound hypocomplementemia for 72 h after inoculation, or treated with phenylbutazone (PB), a competitive antagonist of bacterial chemotactic formylpeptides. Compared to controls, CVF-and PB-treated animals killed when the neutrophil infiltration started (32 h) had a significantly reduced neutrophil infiltration, as measured by kidney MPO activity. This effect disappeared in animals killed 72 h after surgery, when neutrophil infiltration peaked. These data suggest that redundant chemotactic mechanisms triggered neutrophil migration. Inhibiting one of these mechanisms only transiently delayed neutrophil migration but did not affect the peak infiltratio

The value of experimental models in the prophylaxis of bacterial endocarditis

Infective endocarditis (IE) is still a serious medical problem. It not only carries significant mortality during the actual period of endocardial infection, but causes morbidity that may persist beyond the duratio

β-Lactam Resistance Mechanisms of Methicillin-Resistant Staphylococcus aureus

In vitro and in vivo activity of amoxicillin and penicillin G alone or combined with a penicillinase inhibitor (clavulanate) were tested against five isogenic pairs of methicillin-resistant Staphylococcus aureus (MRSA) producing or not producing penicillinase. Loss of the penicillinase plasmid caused an eight times or greater reduction in the MICs of amoxicillin and penicillin G (from ⩾64 to 8 µg/ml), but not of the penicillinase-resistant drugs methicillin and cloxacillin (⩾64 µg/ml). This difference in antibacterial effectiveness correlated with a more than 10 times greater penicillin-binding protein 2a affinity of amoxicillin and penicillin G than of methicillin and a ⩾90% successful amoxicillin treatment of experimental endocarditis due to penicillinasenegative MRSA compared with cloxacillin, which was totally ineffective (P < .001). Amoxicillin was also effective against penicillinase-producing parent MRSA, provided it was combined with clavulanate. Penicillinase-sensitive β-lactam antibiotics plus penicillinase inhibitors might offer a rational alternative treatment for MRSA infection

Biaxial fragmentation of thin silicon oxide coatings on poly(ethylene terephthalate)

Crack patterns of 53 nm and 103 nm thick silicon oxide coatings on poly(ethylene terephthalate) films are analyzed under equibiaxial stress loading, by means of a bulging cell mounted under an optical microscope with stepwise pressurization of film specimens. The biaxial stress and strain are modeled from classical elastic membrane equations, and an excellent agreement is obtained with a finite element method. In the large pressure range, the derivation of the biaxial strain from force equilibrium considerations are found to reproduce accurately the measured data up to 25% strain. The examination of the fragmentation process of the coating under increasing pressure levels reveals that the crack onset strain of the oxide coating is similar to that measured under uniaxial tension. The fragmentation of the coating under biaxial tension is also characterized by complex dynamic phenomena which image the peculiarities of the stress field, resulting in considerable broadening of the fragment size distribution. The evolution of the average fragment area as a function of biaxial stress in the early stages of the fragmentation process is analyzed using Weibull statistics to describe the coating strengt

Clinical experience with Timentin in severe hospital infections

Sixty-four severe infections in hospitalized patients were treated with intravenous Timentin. Most patients (mean age: 50-5 years, range 18-85) had serious underlying conditions such as agranulocytosis, heart failure, cancer, diabetes mellitus, chronic alcoholism or other functional or anatomical abnormalities. Forty-three episodes were bacteriologically proved, and bacteraemia was diagnosed in 18. The sites of infection were: lower respiratory tract (10), upper respiratory tract (10), soft tissues(9), urinary tract (7), bones (6), peritoneal cavity (3), meninges (1) and pelvis (1). Inaddition, 13 episodes of fever and four of septicaemia in patients with agranulocytosis were treated with Timentin plus amilcacin. Overall, 59% of the episodes were cured, 14% improved and 17% failed to respond. In 9% of cases the efficacy of the Timentin was unassessable mainly because of concurrent administration of other antimicrobials. Failure appeared to be more frequent in soft tissue and intra-abdominal infections, in patients infected with bacteria susceptibleto Timentin but resistant to ticarcillin and in patients superinfected with Timentin-resistant strains. Major side effects were haemorrhagic diathesis with platelet dysfunction (1), severe water sodium overload (1), and possibly pancreatitis (1).Other side effects were mild: catheter-related phlebitis, and abnormal but clinically insignificant laboratory test results. Timentin appears to be an effective and safebroad-spectrum combination which compares favourably with third-generation cephalosporins in the treatment of severe hospital infections. More experience is needed to decide whether the some what lower response rate in patients infected with ticarcillin-resistant strains is significan

Predictors of Endocarditis in Isolates from Cultures of Blood Following Dental Extractions in Rats with Periodontal Disease

Rats with periodontitis and catheter-induced aortic valve vegetations underwent dental extractions. Cultures of blood obtained 1 min later showed polymicrobial bacteremia in 19 of 19 rats, mostly due to viridans streptococci (18 of 19), Morganella (15 of 19), group G streptococci (13 of 19), and Staphylococcus aureus (10 of 19). Viridans streptococci circulated in higher numbers than did group G streptococci and S. aureus (P < .01). Three days after dental extractions, 18 of 20 rats had endocarditis. Fifteen (83%) of 18 infections were due to group G streptococci, 9 (50%) of 18 were due to S. aureus, and 2 (11%) of 18 were due to viridans streptococci (P < .05). In vitro, adherence to platelet-fibrin matrices of endocarditis strain 8 of group G streptococcus was two times greater than that of endocarditis strain S. aureus 23 and three to four times greater than that of Streptococcus sanguis 44 and Morganella morganii 93 (P < 10−5). The inoculum size that produced endocarditis in 90% of rats after iv challenge was 105 cfu for group G streptococcus strain 8 and 107 for S. sanguis 4

Dual Microsporidial Infection Due to Vittaforma corneae and Encephalitozoon hellem in a Patient with AIDS

A 46-year-old human immunodeficiency virus-infected Swiss citizen living in Tanzania presented with respiratory, abdominal, and urogenital complaints. Microsporidial spores were isolated from urine and a sinunasal aspirate and were propagated in MRC-5 cell cultures. Western blot analysis and riboprinting identified the sinunasal isolate as Encephalitozoon hellem. Electron microscopic investigation of the urine isolate revealed spores with diplokaryotic nuclei and five to six isofilar coils of the polar tube and sporonts with two or three diplokarya. All stages were enveloped by two membranes, corresponding to a cisterna of host endoplasmic reticulum studded with ribosomes. These characteristics have been described for the genus Vittaforma. Western blot analysis of this isolate revealed a banding pattern identical to that of the Vittaforma corneae reference isolate. Part of the small subunit rRNA gene was amplified, sequenced (239 base pairs), and found to be identical to that of V. corneae. This is the second isolation of V. corneae and the first description of urinary tract infection due to V. corneae in a patient with AID