Cefazolin Concentrations Research Articles

The combined effect of cefazolin and oxytertracycline on biogas production from thermophilic anaerobic digestion of dairy manure

The individual and combined effect of cefazolin (CFZ) and oxytetracycline (OTC) on thermophilic anaerobic digestion (55°C) of dairy manure in batch digesters was investigated. Methane productions from the concentrations tested (30, 60 and 90mgL−1) were compared with no-antibiotic control. CFZ concentrations showed no inhibition (P>0.05) for methane production. The individual OTC and combined CFZ and OTC at concentrations of 30, 60 and 90mgL−1 represented 79.1%, 70.3%, 68.6% (P<0.05) and 88.5%, 82.7%, 70.3% (P<0.05) respectively, of the control values. The high CH4 production, optimal pH and VFA data during digestion indicated the process stability and treatment efficiency.

Superiority of Ceftriaxon to Cefazolin in a Rat Model of Obstructive Jaundice: An Experimental Study

ABSTRACTObjective: The objective of this study was to evaluate the serum and bile concentrations of cefazolin and ceftriaxone at the third and sixth hours in an experimental obstructive jaundice model and to identify the rate of excretion of these antibiotics into the bile. Material and methods: Thirty-two Wistar albino rats were used in this study. The bile and serum levels of cefazolin were measured at the third hour in the A1 group and at the sixth hour in the A2 group, with cefazolin administered as 5 mg/rat; while the bile and serum levels of ceftriaxone were studied at the third hour in the B1 group and at the sixth hour in the B2 group, with ceftriaxone administered as 5 mg/rat. Results: After 3 hr of cefazolin administration, the serum concentration in the A1 group reached a mean of 1.8 μg/ml, while the bile concentration was 90% of the serum concentration, with a mean of 1.6 μg/ml; whereas in the B1 group, the third-hour serum concentration of ceftriaxone was 18.6 μg/ml, while the bile concentration was found to be as high as 330% of this level, i.e., 56 μg/ml. The serum value of cefazolin decreased to 1.4 μg/ml in the A2 group and ceftriaxone decreased to 3.7 μg/ml in the B2 group at the sixth hour. Conclusions: Although the excretory level of cefazolin and ceftriaxone into the bile reaches therapeutic doses, the duration for which these levels are above those required for bactericidal activity is short. Ceftriaxone is better concentrated in the serum and bile than cefazolin.

Cefazolin plasma protein binding and its covariates in neonates

Cefazolin (CFZ) is highly and saturably bound to human serum albumin (HSA) in adults. We aim to describe CFZ protein binding and its covariates in neonates. In neonates to whom intravenous CFZ (50 mg/kg) was administered prior to a surgical procedure, total and unbound CFZ plasma concentrations (mg/l) were determined at 0.5, 2, 4 and 8 h after CFZ administration. Linear and multiple regression analyses were used to document covariates of unbound CFZ fraction. The Wilcoxon signed-rank test was used for the paired analysis of unbound CFZ fractions. In 40 patients with a median weight of 2,767 (range 830-4,200) g and a postmenstrual age (PMA) of 39 (25-45) weeks, 131 samples were collected. The median unbound CFZ fraction was 0.39 (0.10-0.73). Linear regression of unbound CFZ fraction versus unbound CFZ plasma concentration (R (2) = 0.39) had a slope significantly different from zero (p < 0.001). In a multiple regression analysis, albuminaemia, total CFZ concentration, indirect bilirubinaemia and PMA resulted in an R (2) value of 0.496. The median unbound CFZ fraction at the peak concentration (0.46, range 0.28-0.69) was significantly higher compared to the trough level (0.36, range 0.17-0.73) (p < 0.001). The between- and within-patient saturability of CFZ plasma protein binding were documented in neonates. The median unbound CFZ fraction in neonates is higher than in adults and depends partly on albuminaemia, total CFZ concentration, indirect bilirubinaemia and PMA. Integration of CFZ protein binding in future pharmacokinetic/pharmacodynamic research is warranted in order to optimise neonatal CFZ dosing. We recommend protein binding assessment in the neonatal pharmacokinetic evaluation of highly protein-bound or clinically relevant drugs.

Higher Cefazolin Concentrations with Intraosseous Regional Prophylaxis in TKA

Prophylactic antibiotics reduce the risk of deep infection after primary TKA. However, conventional systemic dosing may not provide adequate tissue concentrations against more resistant organisms such as coagulase-negative staphylococci. Regional intravenous administration of antibiotics after tourniquet inflation achieves far higher tissue concentrations but requires foot vein cannulation. The intraosseous route may offer a rapid and reliable method of regional administration. We compared tissue concentrations of cefazolin achieved with systemic versus regional intraosseous administration. Twenty-two patients undergoing primary TKA were randomized into two groups. Group 1 received 1g cefazolin systemically 10 minutes before tourniquet inflation. Group 2 received 1g cefazolin intraosseously in 200mL of normal saline through a tibial cannula after tourniquet inflation and before skin incision. Subcutaneous fat and femoral bone samples were taken at set intervals during the procedure and antibiotic concentrations measured using a validated technique involving high-performance liquid chromatography. The overall mean tissue concentration of cefazolin in subcutaneous fat was 186 ug/g in the intraosseous group and 11 ug/g in the systemic group. The mean tissue concentration in bone was 130 ug/g in the intraosseous group and 11 ug/g in the systemic group. These differences were consistent across all sample time points throughout the procedure. Intraosseous regional administration can achieve concentrations of antibiotic in tissue an order of magnitude higher than systemic administration. Further work is required to determine if this translates into increased efficacy in preventing infection, particularly against coagulase-negative staphylococci.

Effects of Maternal Obesity on Tissue Concentrations of Prophylactic Cefazolin During Cesarean Delivery

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Detection of Cefazolin Based on the Plasma Resonance Absorption of Gold Nanoparticles

The cefazolin can be detected according to the change of solution color resulting from the plasmonic resonance absorption of AuNPs.The absorbance ratio at 520/660 nm of AuNPs is proportional to the concentration of cefazolin in the range of 0.1~5.0 μmol/L with the detection limit of 14 nmol/L.This method could be extended to the determination of cefazolin sodium powder injection,the recovery of cefazolin was in the range of 97.4%~100.2% while the relative standard deviation was less than 6.1%.

Cefazolin Dosing for Surgical Prophylaxis in Morbidly Obese Patients

Cefazolin is used commonly to prevent surgical site infection (SSI) after operations on patients with morbid obesity (MO), but specific dosing guidelines are lacking. We hypothesized that cefazolin 2 g given by intravenous (IV) push over 5 min (IVP) or infusion over 30 min (INF) would suffice for SSI prophylaxis in MO (body mass index [BMI] 40-50 kg/m(2)), and cefazolin 3 g would be sufficient in patients with super-morbid obesity (SMO) (BMI >50 kg/m(2)). Twenty-five patients undergoing elective surgical procedures were given a single dose of cefazolin: Ten with MO received 2 g via IVP (MO2-IVP), five with MO received 2 g via 30-min infusion (MO2-INF), five with SMO received 2 g via infusion (SMO2-INF), and five with SMO received 3 g via infusion (SMO3-INF). Serum cefazolin concentrations were measured 5, 30, 120, and 360 min after initiation of the dose. The half-life of the drug was calculated for each patient, as was the time the concentration was above the minimum inhibitory free concentration (fT>MIC) using 8 mcg/mL as the breakpoint. The protective duration of each cefazolin dose was assessed using the pharmacodynamic target for fT>MIC of 70%. The mean cefazolin concentrations after 30 min were similar in all groups; the mean concentrations at 120 and 360 min were 67.1-84.8 mcg/mL and 22.9-40.8 mcg/mL, respectively. The half-life ranged from 2.3 to 3.6 h and was unaffected by administration method. The protective duration was 5.1 h for MO2-IVP, 4.8 h for MO2-INF, 5.8 h for SMO2-INF, and 6.8 h for SMO3-INF. A single 2-g dose of cefazolin appears to provide antibiotic exposures sufficient for most common general surgical procedures of <5-h duration, regardless of BMI.

Elution Profiles of Cefazolin from PMMA and Calcium Sulfate Beads Prepared from Commercial Cefazolin Formulations

Antibiotic beads have become popular for the treatment of local bacterial infections. The preparation of antibiotic beads from commercial pharmaceutical antibiotics is a convenient method in clinic. The elution characteristics of cefazolin from polymethylmethacrylate (PMMA) (SmartSet HV, Depuy I and Cemfix 3) beads and calcium sulfate beads were studied. Commercial cefazolin formulation was incorporated in PMMA or calcium sulfate at 1 g cefazolin/10 g of matrix substances to form beads. The concentrations of eluted cefazolin during 15 days were greater than MIC for Staphylococcus aureus (ATCC 25923). The eluted cefazolin concentrations were in the range of 3.6 ± 1.2 to 4.6 ± 0.4 mg for PMMA beads and 15.4 ± 1.7 mg for calcium sulfate beads. The accumulated eluted cefazolin from PMMA beads and calcium sulfate beads for 15 days were 34.41 ± 3.93 to 38.67 ± 3.04% and 95.94 ± 3.93%, respectively. The various storage conditions; at room temperature or 4°C, with or without light-protection, for 6 months had little effects on the amounts of eluted cefazolin. The results showed both in-housed cefazolin-PMMA beads and cefazolin-calcium sulfate beads could be the effective tools for the treatment of local bacterial infections.

Are Bone and Serum Cefazolin Concentrations Adequate for Antimicrobial Prophylaxis?

Antimicrobial prophylaxis is considered beneficial for preventing surgical-site infections in clean orthopaedic surgery. However, whether tissue concentrations of cefazolin achieve the minimum inhibitory concentration for the targeted contaminants have yet to be clarified. We asked whether 2g of cefazolin would enable effective serum and bone concentrations relative to the current minimum inhibitory concentration for cefazolin-resistant coagulase-negative Staphylococci and methicillin-sensitive Staphylococcus aureus. We enrolled 43 patients (THA, n=16; TKA, n=27) scheduled for primary THAs and primary TKAs. Subjects were given 2g of cefazolin intravenously before incision. One blood sample and two bone samples were collected from each subject before tourniquet deflation before any additional dose. All samples were assayed at the same laboratory. Minimum inhibitory concentration values were defined based on nationwide surveys. Mean (±standard deviation) serum concentration was 170.3±51.3μg/mL (range, 99.3-370.3μg/mL). Mean bone concentration was 32.3±15.2μg/g (range, 11.4-70.0μg/g) in THA, and 16.0±10.4μg/g (range, 6.3-46.3μg/g) in TKA. All serum and bone concentrations exceeded the minimum inhibitory concentration for methicillin-sensitive S. aureus, but some serum levels were marginal and no bone levels exceeded the minimum inhibitory concentration for cefazolin-resistant coagulase-negative Staphylococcus. Our data suggest intravenous administration of 2g of cefazolin achieves the minimum inhibitory concentration for methicillin-sensitive S. aureus in serum and bone, but not the minimum inhibitory concentration for cefazolin-resistant coagulase-negative Staphylococcus in bone, resulting in a potential risk of deep surgical site infections in THAs and TKAs.

Effects of renal function on the pharmacokinetics and pharmacodynamics of prophylactic cefazolin in cardiothoracic surgery

The purpose of this investigation was to study the effects of renal function on the pharmacokinetics and pharmacodynamics (PK-PD) of free cefazolin administered prophylactically in cardiothoracic surgery. Patients received an initial 2-g dose of cefazolin, followed by 1-g doses 6, 12, 18 and 24 h after the first dose. In patients who underwent cardiopulmonary bypass, 1 g was added to the priming solution. In 35 patients with a normal estimated creatinine clearance (CLcr) ≥50 ml/min, a free cefazolin concentration <4 μg/ml was observed in 11.4, 5.7 and 54.3% of patients before the second dose, at the end and 24 h after operation, respectively. In contrast, only 7.4% of 27 patients with CLcr <49 ml/min had a free cefazolin concentration <4 μg/ml 24 h after the operation. There was a high negative correlation between CLcr and time above the target minimal inhibitory concentration (MIC) when the CLcr was <50 ml/min (r(2) = 0.807), and no correlation when the CLcr was ≥50 ml/min. Renal function has a significant impact on the PK-PD of prophylactic cefazolin in cardiothoracic surgery. The postoperative drug dosing intervals should be <6 h in order to achieve a 100% time above the MIC in patients with CLcr ≥ 50 ml/min.

Pharmacokinetics and protein binding of cefazolin in morbidly obese patients

The aim of this study was to assess the pharmacokinetics and protein binding of cefazolin in morbidly obese patients undergoing bariatric surgery, to study the influence of bodyweight measures and age on pharmacokinetic parameters and to evaluate unbound cefazolin concentrations over time in this population. Twenty morbidly obese patients (bodyweight 112-260 kg, body mass index 38-79 kg m(-2)) were studied following the administration of cefazolin 2 g at induction of anaesthesia. Blood samples were collected up to 4 h post-dosing to determine total and unbound plasma cefazolin concentrations. Non-compartmental pharmacokinetic data analysis was performed. Cefazolin clearance was 4.2 ± 1.0 L h(-1) (mean ± standard deviation) and showed a negative correlation with age (p = 0.003) but not with bodyweight measures (p > 0.05). Volume of distribution was 13.0 ± 3.1 L and correlated positively with bodyweight measures (p ≤ 0.001). Saturable protein binding was observed with a median protein binding of 79% (interquartile range 74-82), which proved similar to reported protein binding in non-obese patients. In all patients, unbound cefazolin concentrations remained above 1 mg L(-1) (minimal inhibitory concentration for 90% (MIC(90)) of methicillin-sensitive isolates of Staphylococcus aureus in Europe) until 4 h post-dosing. Younger age--and not bodyweight--was significantly associated with higher cefazolin clearance. However, as in all patients with bodyweights up to 260 kg, unbound plasma cefazolin concentrations remained above 1 mg L(-1) until 4 h after the intravenous administration of a 2-g dose. As such, re-dosing within 4 h or dosing with another antibiotic class should only be considered in the case of a higher MIC(90) of the local isolates.

Effects of Maternal Obesity on Tissue Concentrations of Prophylactic Cefazolin During Cesarean Delivery

To estimate the adequacy of antimicrobial activity of preoperative antibiotics at the time of cesarean delivery as a function of maternal obesity. Twenty-nine patients scheduled for cesarean delivery were stratified according to body mass index (BMI) category, with 10 study participants classified as lean (BMI less than 30), 10 as obese (BMI 30-39.9), and nine as extremely obese (BMI 40 or higher). All patients were given a dose of 2 g cefazolin 30-60 minutes before skin incision. Antibiotic concentrations from adipose samples, collected after skin incision and before skin closure, along with myometrial and serum samples, were analyzed with microbiological agar diffusion assay. Cefazolin concentrations within adipose tissue obtained at skin incision were inversely proportional to maternal BMI (r=-0.67, P<.001). The mean adipose concentration was 9.4 plus or minus 2.7 micrograms/g in the lean group of women compared with 6.4 plus or minus 2.3 micrograms/g in the obese group (P=.009) and 4.4 plus or minus 1.2 micrograms/g in the extremely obese group (P<.001). Although all specimens demonstrated therapeutic cefazolin levels for gram-positive cocci (greater than 1 microgram/g), a considerable portion of obese and extremely obese did not achieve minimal inhibitory concentrations of greater than 4 micrograms/g for Gram-negative rods in adipose samples at skin incision (20% and 33.3%, respectively) or closure (20.0% and 44.4%, respectively). No significant difference in cefazolin concentration was observed in mean closure adipose, myometrial, or serum specimens across the BMI categories. Pharmacokinetic analysis suggests that present antibiotic prophylaxis dosing may fail to provide adequate antimicrobial coverage in obese patients during cesarean delivery. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00980486. II.

Antibiotic dosing in the 'at risk' critically ill patient: Linking pathophysiology with pharmacokinetics/pharmacodynamics in sepsis and trauma patients

BackgroundCritical illness, mediated by trauma or sepsis, can lead to physiological changes that alter the pharmacokinetics of antibiotics and may result in sub-therapeutic concentrations at the sites of infection. The first aim of this project is to identify the clinical characteristics of critically ill patients with significant trauma that have been recently admitted to ICU that may predict the dosing requirements for the antibiotic, cefazolin. The second aim of this is to identify the clinical characteristics of critically ill patients with sepsis that may predict the dosing requirements for the combination antibiotic, piperacillin-tazobactam.Methods/DesignThis is an observational pharmacokinetic study of patients with trauma (cefazolin) or with sepsis (piperacillin-tazobactam). Participants will have samples from blood and urine, collected at different intervals. Patients will also have a microdialysis catheter inserted into subcutaneous tissue to measure interstitial fluid penetration of the antibiotic. Participants will be administered sinistrin, indocyanine green and sodium bromide as well as have cardiac output monitoring performed and tetrapolar bioimpedance to determine physiological changes resulting from pathology. Analysis of samples will be performed using validated liquid chromatography tandem mass-spectrometry. Pharmacokinetic analysis will be performed using non-linear mixed effects modeling to determine individual and population pharmacokinetic parameters of antibiotics.DiscussionThe study will describe cefazolin and piperacillin-tazobactam concentrations in plasma and the interstitial fluid of tissues in trauma and sepsis patients respectively. The results of this study will guide clinicians to effectively dose these antibiotics in order to maximize the concentration of antibiotics in the interstitial fluid of tissues.

42: Effects of maternal obesity on tissue concentrations of prophylactic cefazolin during cesarean delivery

Surgical site infections remain a frequent complication of cesarean delivery despite antimicrobial prophylaxis, causing increased mortality, morbidity, and costs. No prior investigations have evaluated the tissue penetration and concentrations of preoperative antibiotics at the time of cesarean delivery as a function of maternal obesity.

The concentration of antibiotic in fresh-frozen bone graft

We investigated the antibiotic concentration in fresh-frozen femoral head allografts harvested from two groups of living donors. Ten samples were collected from patients with osteoarthritis of the hip and ten from those with a fracture of the neck of the femur scheduled for primary arthroplasty. Cefazolin (1 g) was administered as a pre-operative prophylactic antibiotic. After storage at -80 degrees C for two weeks the pattern of release of cefazolin from morsellised femoral heads was evaluated by an in vitro broth elution assay using high-performance liquid chromatography. The bioactivity of the bone was further determined with an agar disc diffusion and standardised tube dilution bioassay. The results indicated that the fresh-frozen femoral heads contained cefazolin. The morsellised bone released cefazolin for up to four days. The concentration of cefazolin was significantly higher in the heads from patients with osteoarthritis of the hip than in those with a fracture.Also, in bioassays the bone showed inhibitory effects against bacteria.We concluded that allografts of morsellised bone from the femoral head harvested from patients undergoing arthroplasty of the hip contained cefazolin, which had been administered pre-operatively and they exhibited inhibitory effects against bacteria in vitro.

Resistance carrying plasmid in a traumatic wound

To isolate and identify antibiotic-resistant bacteria from the exudate of a complex wound and determine if antibiotic resistance genes are chromosomal or plasmid borne. Antibiotic resistant bacteria from wound exudate of a single clinical sample were selected on agar media with ampicillin. A single colony was further screened for resistance to kanamycin by antibiotic-supplemented agar and to other antibiotics by an automated Phoenix instrument. Identification of the isolate was carried out by biochemical profiling and by 16S rDNA analysis. Approximately 51% of total bacteria in the wound exudate with identical colony morphotype were resistant to 100 microg/ml of ampicillin. A single colony from this population also demonstrated resistance to 50 microg/ml of kanamycin on kanamycin-supplemented agar. Further antimicrobial sensitivity testing by the Phoenix instrument indicated resistance to inhibitory concentrations of amoxicillin-clavulanate, ampicillin-sulbactam, cefazolin, gentamicin, nitrofurantoin, tobramycin, and trimethoprim-sulfamethoxazole. Biochemical and 16S rDNA analysis identified this bacterial isolate as a member of genus Enterobacter. A plasmid preparation from this isolate successfully transferred ampicillin and kanamycin resistance to E. coli competent cells. E. coli transformants displayed two resistance phenotypes and the plasmids from these transformants displayed two different restriction type patterns, with one correlating to ampicillin and kanamycin resistance and the other only to ampicillin resistance. A multiple antibiotic-resistant Enterobacter spp. from the wound fluid of a clinical sample was found to carry an antibiotic-resistant plasmid in a closely related species E. coli. The presence of antibiotic resistance plasmid in Enterobacteria that are part of the normal microbial flora of the human gut and skin could lead to the spread of resistance phenotype and emergence of antibiotic resistant pathogens. This study suggests normal human microbial fl ora could be a potential reservoir for resistance genes.

Cefazolin embedded biodegradable polypeptide nanofilms promising for infection prevention: a preliminary study on cell responses.

Implant-associated infection is a serious complication in orthopedic surgery, and endowing implant surfaces with antibacterial properties could be one of the most promising approaches for preventing such infection. In this study, we developed cefazolin loaded biodegradable polypeptide multilayer nanofilms on orthopedic implants. We found that the amount of cefazolin released could be tuned. A high local concentration of cefazolin was achieved within the first a few hours and therefore may inhibit bacterial colonization in the critical postimplantation period. The developed cefazolin loaded nanofilms showed their in vitro efficacy against Staphylococcus aureus; the more antibiotics loaded, the longer the nanocoated implant had antibacterial properties. More interestingly, antibiotic-loaded polypeptide multilayer nanofilms also improved osteoblast bioactivity including cell viability and proliferation. These findings suggested that biodegradable polypeptide multilayer nanofilms as antibiotic carriers at the implant/tissue interface are compatible with human cells such as osteoblasts and bactericidal to bacteria such as S. aureus. These characteristics could be promising for preventing implant-associated infection and potentially improving bone healing.

Preoperative administration of cephalosporins for elective caesarean delivery

Antibiotic prophylaxis means administration of antibiotics in prevention of infections. To investigate the efficacy of a single dose preoperative administration of ceftriaxone and cefazolin in the prevention of intra- and postoperative infections in the parturients without high risk of inflammation. The first group of 45 pregnant and 4 non-pregnant women were preoperatively administered ceftriaxone in a dose of 2 g, i.v., 10 minutes before the planned surgery. The second group of 45 pregnant and 4 non-pregnant women were preoperatively administered cefazolin in a dose of 2 g i.v., 10 minutes before the planned surgery. The concentrations of antibiotics were estimated immediately and 6 hours following the operation, as well as in the amniotic fluid and umbilical cord in the group of pregnant women. The estimation of antibiotic concentration was done by the method of liquid chromatography. The mean concentrations of antibiotics in the patients following the elective caesarean section were as follows: ceftriaxone--22.7 microg/I. vs cefazolin--44.8 microg/l. Six hours later, the concentration of antibiotic decreased, but the concentration of cefazolin was still over the MIC for sensitive bacteria. The mean concentrations of antibiotics following gynaecological surgery in the non-pregnant patients were as follows: ceftriaxone--12.0 microg/I vs cefazolin--30.1 microg/l. Six hours later, the concentration of antibiotic decreased. It is most optimal to administer a single-dose of the first generation cephalosporins -cefazolin- immediately following the clamping of the umbilical cord as well as in preoperative prophylaxis in gynaecological operations.

Role of pathogenic oral flora in postoperative pneumonia following brain surgery

BackgroundPost-operative pulmonary infection often appears to result from aspiration of pathogens colonizing the oral cavity. It was hypothesized that impaired periodontal status and pathogenic oral bacteria significantly contribute to development of aspiration pneumonia following neurosurgical operations. Further, the prophylactic effects of a single dose preoperative cefazolin on the oral bacteria were investigated.MethodsA matched cohort of 18 patients without postoperative lung complications was compared to 5 patients who developed pneumonia within 48 hours after brain surgery. Patients waiting for elective operation of a single brain tumor underwent dental examination and saliva collection before surgery. Bacteria from saliva cultures were isolated and periodontal disease was scored according to type and severity. Patients received 15 mg/kg cefazolin intravenously at the beginning of surgery. Serum, saliva and bronchial secretion were collected promptly after the operation. The minimal inhibitory concentrations of cefazolin regarding the isolated bacteria were determined. The actual antibiotic concentrations in serum, saliva and bronchial secretion were measured by capillary electrophoresis upon completion of surgery. Bacteria were isolated again from the sputum of postoperative pneumonia patients.ResultsThe number and severity of coexisting periodontal diseases were significantly greater in patients with postoperative pneumonia in comparison to the control group (p = 0.031 and p = 0.002, respectively). The relative risk of developing postoperative pneumonia in high periodontal score patients was 3.5 greater than in patients who had low periodontal score (p < 0.0001). Cefazolin concentration in saliva and bronchial secretion remained below detectable levels in every patient.ConclusionPresence of multiple periodontal diseases and pathogenic bacteria in the saliva are important predisposing factors of postoperative aspiration pneumonia in patients after brain surgery. The low penetration rate of cefazolin into the saliva indicates that its prophylactic administration may not be sufficient to prevent postoperative aspiration pneumonia. Our study suggests that dental examination may be warranted in order to identify patients at high risk of developing postoperative respiratory infections.

The Chromosomal Toxin Gene yafQ Is a Determinant of Multidrug Tolerance for Escherichia coli Growing in a Biofilm

Escherichia coli is refractory to elevated doses of antibiotics when it is growing in a biofilm, and this is potentially due to high numbers of multidrug-tolerant persister cells in the surface-adherent population. Previously, the chromosomal toxin-antitoxin loci hipBA and relBE have been linked to the frequency at which persister cells occur in E. coli populations. In the present study, we focused on the dinJ-yafQ-encoded toxin-antitoxin system and hypothesized that deletion of the toxin gene yafQ might influence cell survival in antibiotic-exposed biofilms. By using confocal laser scanning microscopy and viable cell counting, it was determined that a Delta yafQ mutant produced biofilms with a structure and a cell density equivalent to those of the parental strain. In-depth susceptibility testing identified that relative to wild-type E. coli, the Delta yafQ strain had up to a approximately 2,400-fold decrease in cell survival after the biofilms were exposed to bactericidal concentrations of cefazolin or tobramycin. Corresponding to these data, controlled overexpression of yafQ from a high-copy-number plasmid resulted in up to a approximately 10,000-fold increase in the number of biofilm cells surviving exposure to these bactericidal drugs. In contrast, neither the inactivation nor the overexpression of yafQ affected the tolerance of biofilms to doxycycline or rifampin (rifampicin). Furthermore, deletion of yafQ did not affect the tolerance of stationary-phase planktonic cells to any of the antibacterials tested. These results suggest that yafQ mediates the tolerance of E. coli biofilms to multiple but specific antibiotics; moreover, our data imply that this cellular pathway for persistence is likely different from that of multidrug-tolerant cells in stationary-phase planktonic cell cultures.