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PubMed1983

Reduction of post-cesarean section infectious morbidity by means of antibiotic irrigation.

The effectiveness of antibiotic irrigation in reducing post-cesarean section infectious morbidity was studied in a prospective, randomized, double-blind trial. One hundred twenty-eight patients were divided into three groups and irrigated with either cefoxitin solution, cephapirin solution, or saline. Following delivery of the placenta, the uterine cavity and incision, bladder flap, pelvic gutters, and subcutaneous tissue of the patients were irrigated. There was a significant reduction in total infectious morbidity (p less than 0.02) and wound infection (p less than 0.04) when antibiotic use was compared to the saline control. No statistical difference in the effectiveness of the two antibiotics could be demonstrated. No adverse effects were noted. Antibiotic irrigation is a safe and effective method in reducing infectious morbidity of the parturient patient.

Bacterial Infections↗
PubMed1995

Bacterial wound colonization after broad-spectrum versus narrow-spectrum antibiotics.

Broad-spectrum versus narrow-spectrum antibiotic prophylaxis for patients who undergo cardiac operations is variously advocated to reduce the incidence of all infections or, conversely, to prevent resistant superinfections. Previous studies of prophylaxis have shown a reduction in the incidence of staphylococcal infections with some increased resistance. We studied preoperative and postoperative wound colonization as a surrogate for infection. Among 78 patients undergoing cardiac procedures, the type of prophylaxis was allocated as follows: narrow-spectrum (nafcillin), 24 patients; midspectrum (cephapirin), 26 patients; and broad-spectrum (ceftriaxone), 28 patients. Seventeen patients who underwent other procedures received no antibiotics and served as controls. Cultures of the operative site were done preoperatively, and 3 and 6 days postoperatively. The incidence of preoperative skin colonization with staphylococci was identical (95%) in all groups. Postoperatively, more patients receiving nafcillin (48%) were culture-negative for all organisms than were either of the other groups receiving antibiotics (27% and 22%) (p < 0.05). Gram-negative bacilli were infrequent colonizers and neither did the incidence of infection with these organisms increase nor did resistance develop in any group. The infection rates were not different among the treatment groups. Thus, a narrow-spectrum antistaphylococcal penicillin may offer an advantage in terms of both prophylaxis for cardiac operations and hospital costs.

Bacteria↗
PubMedDate not supplied

A review of cephalosporin metabolism: a lesson to be learned for future chemotherapy.

The historical background information concerning the metabolism of cephalosporins and selected other antiinfectives was reviewed as a preface to discussion concerning desacetyl-cefotaxime (dCTX), a metabolite of cefotaxime (CTX) sodium. Cephalothin and cephapirin were metabolized at the 3-position to less active desacetyl forms. However, the parent drugs and their metabolites interact in a favorable manner resulting in dominant additive or synergist inhibition of susceptible bacterial pathogens. Similarly, CTX plus dCTX have been described as being synergist in their activity against greater than 70% of Enterobacteriaceae or staphylococci and greater than 80% of anaerobic bacteria. Antagonism was rare with only two species and of no clinical significance. More recently, reported studies showed enhanced activity of CTX/dCTX against pathogens producing meningitis compared to ceftriaxone and other contemporary therapeutic agents. The dCTX compound was classified as a drug with a potency superior to a "second-generation" cephalosporin and possessed greater beta-lactamase stability against some enzymes compared to CTX. These features may explain low reported rates of superinfections and adverse side-effects, including resistance arising on chemotherapy. Physicians are cautioned to take into account the potential favorable effects of drug metabolites on antimicrobial spectrum, potency and applied pharmacokinetics. In the case of CTX/dCTX, the laboratory results for CTX will always underestimate its value or potency because of the contribution of the metabolite.

4-Quinolones↗
PubMed2004

Persistence of a Staphylococcus aureus small-colony variant under antibiotic pressure in vivo.

Staphylococcus aureus small-colony variants (SCVs) have been implicated in chronic and persistent infections. Bovine mastitis induced by S. aureus is an example of an infection difficult to eradicate by conventional antimicrobial therapies. In this study, the ability to colonize mouse mammary glands and persist under antibiotic treatment was assessed for S. aureus Newbould and an isogenic hemB mutant, which exhibited the classical SCV phenotype. The hemB mutant showed a markedly reduced capacity to colonize tissues. However, although the hemB mutant was as susceptible as S. aureus Newbould to cephapirin in vitro, it was over a 100 times more persistent than the parental strain in the mammary glands when 1 or 2 mg kg(-1) doses were administrated. These results suggest that, although the hemB mutant has a reduced ability to colonize mammary glands, the SCV phenotype may account for the persistence of S. aureus under antibiotic pressure in vivo.

Animals↗
PubMed2005

Inflammatory cell infiltration as an indicator of Staphylococcus aureus infection and therapeutic efficacy in experimental mouse mastitis.

Staphylococcus aureus intramammary colonization of the mouse mammary gland induces migration of polymorphonuclear neutrophils (PMNs) similar to that observed during bovine mastitis. In the present study, a method combining acridine orange staining, fluorescence microscopy and computer-assisted image analysis has been developed to quantitate PMN infiltration in a mouse model of mastitis. This was carried out using paraffin embedded sections, and using this method, we showed that the presence of PMNs increased with the number of bacteria present in tissues. Nearly 400 and 1100 times more PMNs were counted in the mammary gland tissue after 12 and 24 h of infection, respectively, compared to mice infected for 6 h. Treatment with the antibiotic cephapirin at 10 or 25 mg/kg reduced PMN infiltration by 71 and 85%, respectively. In conclusion, this method can be used to quantitate PMN infiltration as a marker of inflammation and bacterial burden in infected tissue sections.

Acridine Orange↗
PubMed2004

Mouse mastitis model of infection for antimicrobial compound efficacy studies against intracellular and extracellular forms of Staphylococcus aureus.

Despite the general in vitro susceptibility of Staphylococcus aureus isolates that cause infectious bovine mastitis, the pathogen remains difficult to eradicate with the available antibiotics. The capacity to survive intracellularly has been proposed as a factor contributing to the persistence of S. aureus in the bovine mammary gland. The costs associated with the use of cows or goats to assess the in vivo efficacy of new antibacterial compounds constitute a major drawback. Therefore, in the present study, a mouse model of intramammary infection has been characterized for in vivo testing of new experimental drugs. An inoculum of 100 CFU of S. aureus per gland caused an important level of infection with minimal tissue damage as observed at 24 h post-inoculation. By microscopy, polymorphonuclear neutrophil cell infiltration of the infected mammary glands was observed to increase over time. At 12-24 h of infection, the pathogen was primarily found alive and dividing in neutrophils and occasionally within mammary epithelial cells. Intramuscular or intravenous injections of cephapirin at t = 0 and 10 h reduced the number of CFU/g of gland in a dose-dependent manner. In conclusion, the mouse model of infectious mastitis proposed here is suitable for primary evaluation of experimental drugs after parenteral treatment of intramammary infection with a pathogen such as S. aureus that presents both intracellular and extracellular phases of growth.

Animals↗
PubMedDate not supplied

Effect of hemostatic agents in canine gastric serosal blood vessels.

The efficacy of various sclerotherapeutic agents in the control of acute bleeding, via subserosal injection, was assessed in 10 dogs. Blood flow rate (BFR) from severed gastric serosal vessels (diameter, 1.6 to 2.2 mm) was measured for 3 min (ml/min) for a control group and the agent used. The agents tested were 5 ml of normal saline (NS), 5 ml of 3% hypertonic saline (HS), 5 ml of 1:10,000 epinephrine in NS, 5 ml of 1:10,000 epinephrine/HS, 5 ml of 1:20,000 epinephrine/HS, 2 ml of old thrombin "cocktail" (thrombin, cephapirin + 1% tetradecyl), and 2 ml of fresh thrombin cocktail (total seven). One agent was tested per dog; there were one to two dogs in each subgroup. All of the agents showed significant reduction in BFR (except old thrombin) when compared with BFR of control vessels. The reduction ranged from 30% to more than 75% after 1:10 epinephrine/HS. Complete hemostasis was achieved in up to 47% of vessels using 1:20 epinephrine/HS. Overall, the epinephrine solutions achieved the best results. No systemic effects were observed with the use of any of the agents. Histological studies showed that epinephrine caused mild tissue damage, whereas the cocktail caused significant tissue necrosis. This serosal vessel model permits comparison of the effectiveness of each agent; however, clinical extrapolation to mucosal vessels in a patient and the long-term histological changes are not known.

Animals↗
PubMed1981

Cyst fluid antibiotic concentrations in polycystic kidney disease: differences between proximal and distal cysts.

The concentrations of several antibiotics were measured in the cyst fluid of six adult patients with polycystic kidney disease. Seventy-nine cysts were aspirated at surgery or autopsy. Sixty-one cysts could be categorized as arising from the proximal nephron and 16 from the distal nephron by cyst fluid to serum sodium ratios. Serum, urine, and cyst fluid were simultaneously analyzed for sodium, creatinine, and various antibiotics. Gentamicin, tobramycin, cephapirin, and ticarcillin were either undetectable or present in low concentrations in renal cysts. Cyst fluid antibiotic concentrations did not correlate with cyst volume or creatinine clearance. Cysts of proximal nephron origin had higher antibiotic concentrations than distal cysts. In one patient with normal renal function, inulin was undetectable in renal cysts after a continuous 36-hour i.v. infusion. Para-aminohippurate, however, was detected in the renal cysts of this patient. These data help explain the poor clinical response of infected renal cysts to antibiotic therapy. They also suggest that antibiotics and other solutes may enter cyst fluid across tubular cells in addition to entry by glomerular filtration.

Anti-Bacterial Agents↗
PubMed2004

Structural determinants of substrate binding to Bacillus cereus metallo-beta-lactamase.

Binding and hydrolysis of the beta-lactams cefotaxime, cephapirin, imipenem, and benzylpenicillin by the metallo-beta-lactamase from Bacillus cereus were studied by presteady state kinetic measurements. In all cases, the substrate was unmodified in the most populated reaction intermediate, and no chemically modified substrate species accumulated to a detectable amount. The cephalosporins tested showed similar formation rate constants for this intermediate, and they differed mostly in their decay rates. Formation of a non-productive enzyme.substrate complex was detected for imipenem. The substrate binding differences can be accounted for by considering the structural features of each substrate. The apoenzyme could not bind any of the substrates, but binding was restored when the apoenzyme was reconstituted with Zn(II), revealing that the metal ions are the main determinants of substrate binding. This evidence is in line with the lack of an optimized substrate recognition patch in B1 and B3 metallo-beta-lactamases that provides a broad substrate spectrum.

Anti-Bacterial Agents↗
PubMed1988

Surgical complications related to insertion of penile prostheses with emphasis on infection and cost.

We initiated a prospective study of penile prosthesis implant surgery to evaluate risk factors for infection and other complications. Twenty-one patients admitted for surgery or related complications were evaluated over a seven-month period. The two types of penile prostheses implanted were (1) inflatable and (2) semi-rigid. Nine of 21 patients (43%) developed postoperative complications. Although cephapirin and gentamicin were given prophylactically, four of nine patients had four wound infections and one case of pneumonia. One case of Bacteroides fragilis bacteremia was due to stool incontinency during surgery. In two of the wound infections, removal and reinsertion of the prosthesis was necessary. Other complications included hypotension during surgery, prosthesis malfunction and malposition, and urethral tears. There were no significant associations between infection and age, length of surgery, or type of prosthesis used. These complications contributed to prolonged hospital stay and readmission (87 extra days for the infected patients at a cost of $44,000). Antibiotic costs to treat the infections totaled $1,900. Prospective evaluation by infection control practitioners of various elective surgeries can be useful in quantitating the complication rate and targeting patients at risk, with the goal of minimizing hospital costs.

Cephapirin↗
PubMed1982

Effect of the ratio of surface area to volume on the penetration of antibiotics in to extravascular spaces in an in vitro model.

The penetration of cephapirin into extravascular spaces of various volumes and ratios of surface area to volume (SA/V) was studied in an in vitro kinetic model. The SA/V ratio was found to be an important determinant of the kinetics of these spaces. The greater the surface area in relation to the volume of the extravascular space, the more closely its kinetics mimicked those of the intravascular space-that is, the higher the absolute peak concentration of drug achieved in the extravascular space, the greater the peak-to-trough fluctuation and the more quickly the peak concentration of drug was reached. Extravascular spaces with similar SA/V ratios demonstrated similar kinetics. Data from various models of extravascular fluid in humans and animals were reviewed, and the kinetics of these extravascular spaces were also found to be determined, at least in part, by the SA/V ratios of the spaces.

Cephalosporins↗
PubMed1996

Therapeutic and prophylactic effect of prepartum antibiotic infusion in heifers.

Prepartum bacteriologic examination of secretions from 42 dairy heifers 12-14 weeks prepartum revealed a total of 24 Staphylococcus aureus infected quarters, 53 Staphylococcus species infected quarters, and 20 Streptococcus species infected quarters. Prepartum intramammary therapy of primigravid dairy heifers with two commercially available dry cow antibiotics (penicillin-novobiocin or cephapirin) resulted in cure rates of 94%, 97%, and 100% for S. aureus, Staphylococcus species, and Streptococcus species intramammary infections (IMI), respectively. No protective effect was observed for dry cow treatment of uninfected quarters of heifers for any of the antibiotic preparations. No antibiotic was detectable in heifer secretions collected at parturition indicating that antibiotic concentrations may have fallen below protective levels prior to parturition.

Animals↗
PubMed1976

Comparison of thrombophlebitis associated with three cephalosporin antibiotics.

A double-blind study with volunteers was performed to determine the incidence and severity of thrombophlebitis associated with cephalothin, cephapirin, cefamandole, and a water control. Although there were no statistical differences in the incidence of thrombophlebitis, cephalothin resulted in significantly more severe thrombophlebitis compared with the other agents.

Cephalosporins↗
PubMed1976

Influence of cephalosporin antibiotics on blood coagulation and platelet function.

Administration of cephalothin to normal volunteers in maximal doses of 300 mg/kg per day resulted in a combined defect of platelet function and blood coagulation. No such abnormalities were evident after infusion of cefazolin or cephapirin at a maximal dosage of 200 mg/kg per day. The observed thrombocytopathy was similar to but less severe than that induced by carbenicillin or ticarcillin and was not reflected by a prolonged bleeding time test or impaired prothrombin consumption. Moreover, it was not a consistent finding in those persons receiving cephalothin. A separate defect involving blood coagulation appeared to result from delayed fibrinogen-fibrin polymerization and was evidenced by extended values of the activated partial thromboplastin and thrombin time tests. It remains uncertain whether the abnormalities described may constitute clinically important hemostatic disorders in patients with normal renal function receiving large doses of cephalosporin antibiotics.

Blood Coagulation↗
PubMed1976

In vitro activity of BL-s640 against gram-negative bacilli and Staphylococcus aureus compared with activity of four other semisynthetic cephalosporins.

The in vitro activity of BL-S640 (cefatrizine) was determined against 674 recent clinical isolates of Staphylococcus aureus and Enterobacteriaceae. Activity against S. aureus was less than that of cephapirin, cephalothin, and cefazolin, but greater than that of cephalexin. Activity against gram-negative isolates was variable: BL-S640 was slightly less potent than cefazolin against Escherichia coli and Klebsiella, but more active than the other compounds. As for the more resistant gram-negative genera, BL-S640 was significantly superior to the control cephalosporins. The effect of inoculum size on the antibacterial activity was moderate for most organisms except Enterobacter, Providencia stuartii, and indole-positive Proteus, the median minimal inhibitory concentrations of which were 6 to 27 times lower when determined with a 10(-4)-diluted culture compared with the undiluted one. The stability in aqueous solution at 37 C was remarkably high at the lower pH values, but low at the neutral point.

Cefazolin↗
PubMed1976

In vitro and in vivo comparative evaluations of injectable cephalosporin derivatives and ampicillin.

The in vitro and in vivo activity of the 5 injectable cephalosporins, cefazolin, cephaloridine, cephalothin, cephapirin, cephacetrile, and ampicillin was compared. No gram-positive organisms resistant to any of the cephalosporin derivatives were encountered. The MIC of ampicillin for gram-positive organisms was distributed over a wide range. The antibacterial activity of cefazolin, cephaloridine and ampicillin was high against gram-negative organisms. Ampicillin was potently effective especially against P. mirabilis and cefazolin especially against K. pneumoniae. The protecting effect of the 5 cephalosporins on experimental infections in mice was compared. The effect of cefazolin and cephaloridine was more marked than that of the others. These results may be explained by the fact that the other 3 cephalospoirins are rapidly metabolized in the living body.

Ampicillin↗
PubMed1985

Variation in prophylactic antibiotic use in pediatric orthopedic surgery.

Fifty-two pediatric patients undergoing orthopedic surgery were evaluated to determine the pattern of prophylactic antibiotic use. Of the 50 patients receiving antibiotics, 43 patients were given the antibiotic prior to surgery; 38 patients received the drug within two hours prior to surgery. All patients received the postoperative antibiotic for a duration ranging from 2 to 14 days. Thirty-one patients received the postoperative antibiotic for longer than 48 hours without documentation of infection. Cephapirin and/or cefazolin were the most common antibiotics used. Due to fixed postoperative doses (0.5-2 g), the dose/kg/d exceeded the maximum recommended therapeutic doses in one-third of the patients. The results of this study illustrate that the use of prophylactic antibiotics in pediatric orthopedic surgery can be improved to maximize benefits and minimize costs and the potential for adverse effects. Until data from controlled studies become available, it seems appropriate to follow the Centers for Disease Control guidelines in establishing hospital policy for surgical prophylaxis.

Adolescent↗
PubMed2002

A luminescent Escherichia coli biosensor for the high throughput detection of beta-lactams.

A group-specific bioluminescent Escherichia coli strain for studying the action of beta-lactam antibiotics is described. The strain contains a plasmid, pBlaLux1, in which the luciferase genes from Photorhabdus luminescens are inserted under the control of the beta-lactam-responsive element ampR/ampC from Citrobacter freundii. In the presence of beta-lactams, the bacterial cells are induced to express the luciferase enzyme and three additional enzymes generating the substrate for the luciferase reaction. This biosensor for beta-lactams does not need any substrate or cofactor additions, and the bioluminescence can be measured very sensitively in real time by using a luminometer. Basic parameters affecting the light production and induction in the gram-negative model organism E. coli SNO301/pBlaLux1 by various beta-lactams were studied. The dose-response curves were bell shaped, indicating toxic effects for the sensor strain at high concentrations of beta-lactams. Various beta-lactams had fairly different assay ranges: ampicillin, 0.05-1.0 microg/ml; piperacillin, 0.0025-25 microg/ml; imipenem, 0.0025-0.25 microg/ml; cephapirin, 0.025-2.5 microg/ml; cefoxitin, 0.0025-1.5 microg/ml; and oxacillin, 25-500 microg/ml. Also, the induction coefficients (signal over background noninduced control) varied considerably from 3 to 158 in a 2-hour assay. Different non-beta-lactam antibiotics did not cause induction. Because the assay can be automated using microplate technologies, the approach may be suitable for higher throughput analysis of beta-lactam action.

Ampicillin↗