The potential impact of discrepancies between automated susceptibility platforms and other testing metho`dologies for cefazolin in the treatment of Enterobacterales bloodstream infections.

Revised breakpoints for cefazolin (CFZ) against Enterobacterales may be difficult to implement with current automated susceptibility testing platforms and could falsely report organisms as susceptible, leading to inappropriate treatment for bloodstream infections (BSI). This was a retrospective cohort of adult patients with Enterobacterales BSI reported CFZ susceptible per Vitek®2. The primary outcome was the percentage susceptible by minimum inhibitory concentration (MIC) Gradient Test Strips and disk diffusion. Secondary outcomes included clinical outcomes between CFZ and non-CFZ-treated patients. Among 195 isolates reported CFZ-susceptible per Vitek®2, 84 (43.1%) were CFZ susceptible by MIC Gradient Test Strips vs 119 (61%) by disk diffusion. No difference was noted in 30-day all-cause mortality, secondary complications, or 30-day readmissions. Treatment failure was less likely to occur with source control (adjusted OR 0.06) and infectious disease consult (adjusted OR 0.37). There was a large degree of discrepancy between automated testing and manual methods; the clinical impact of this discrepancy warrants further investigation.

A randomized trial regarding antimicrobial prophylaxis (AMP) in transurethral resection of bladder tumor (TURB).

PURPOSE: To determine whether omitting antimicrobial prophylaxis (AMP) in TURB is safe in patients undergoing TURB without an indwelling pre-operative catheter/nephrostomy/DJ and a negative pre-operative urinary culture. MATERIALS AND METHODS: A multi-centered randomized controlled trial (RCT) from 17-09-2017 to 31-12-2019 in 5 hospitals. Patients with a pre-operative indwelling catheter/DJ-stent or nephrostomy and a positive pre-operative urinary culture (> 104 uropathogens/mL) were excluded. Post-operative fever was defined as body temperature ≥ 38.3 °C. A non-inferiority design with a 6% noninferiority margin and null hypothesis (H0) that the infection risk is at least 6% higher in the experimental (E) than in the control (C) group; H0: C (AMP-group) - E (no AMP-group) ≥ Δ (6% noninferiority margin). A multivariable, logistic regression was performed for AMP and post-TURB fever with covariates: tumor size and (clot-) retention. The R Project® for statistical computing was used for statistical analysis and a p value of 0.05 was considered as statistically significant. RESULTS: 459 Patients were included and 202/459 (44.1%) received AMP vs 257/459 (55.9%) without AMP. Fever occurred in 6/202 [2.9%; 95% CI (1.2-6.6%)] patients with AMP vs 8/257 [3.1%; 95% CI (1.5%-6.1%)] without AMP (p = 0.44). Multivariable, logistic regression showed no significant harm in omitting AMP when controlled for (clot-)retention and tumor size (p = 0.85) and an adjusted risk difference in developing post-TURB fever of 0.0016; 95% CI [- 0.029; 0.032]. CONCLUSION: Our data suggest the safety of omitting AMP in patients undergoing TURB without an indwelling, pre-operative catheter/nephrostomy/DJ and a negative pre-operative urinary culture.

Antimicrobial Prophylaxis in Transurethral Resection of the Prostate: Results of a Randomized Trial.

PURPOSE: We sought to determine whether omitting antimicrobial prophylaxis is safe in patients undergoing transurethral resection of the prostate without preoperative pyuria and a preoperative catheter. MATERIALS AND METHODS: We conducted a multicenter randomized controlled trial from September 17, 2017 until December 31, 2019 in 5 hospitals. Patients with pyuria (>100 white blood cells/ml) and a preoperative indwelling catheter were excluded. Postoperative fever was defined as a body temperature ≥38.3C. A noninferiority design was used with a 6% noninferiority margin and null hypothesis (H0) that the infection risk is at least 6% higher in the experimental (E) than in the control (C) group; H0: C (antimicrobial prophylaxis group) - E (no antimicrobial prophylaxis group) ≥ Δ (6% noninferiority margin). A multivariable, logistic regression was performed regarding posttransurethral resection of the prostate fever and antimicrobial prophylaxis with co-variates: (clot-)retention and operating time. The R Project® for statistical computing was used and a p value of 0.05 was considered as statistically significant. RESULTS: Of the patients 474 were included for multivariable analysis and 211/474 (44.5%) received antimicrobial prophylaxis vs 263/474 (55.5%) patients without antimicrobial prophylaxis. Antibiotics were fluoroquinolones in 140/211 (66.4%), cephazolin in 58/211 (27.5%) and amikacin in 13/211 (6.2%) patients. Fever occurred in 9/211 (4.4%) patients with antimicrobial prophylaxis vs 13/263 (4.9%) without antimicrobial prophylaxis (p=0.8, risk difference 0.006 [95% CI -0.003-0.06, relative risk 1.16]). We were able to exclude a meaningful increase in harm associated with omitting antimicrobial prophylaxis (p=0.4; adjusted risk difference 0.016 [95% CI -0.02-0.05]). CONCLUSIONS: Our data demonstrate the safety of omitting antimicrobial prophylaxis in patients undergoing transurethral resection of the prostate without preoperative pyuria and a preoperative indwelling catheter.

Population pharmacokinetics of cefazolin in critically ill children infected with methicillin-sensitive Staphylococcus aureus.

OBJECTIVES: Cefazolin is one of curative treatments for infections due to methicillin-sensitive Staphylococcus aureus (MSSA). Both growth and critical illness may impact the pharmacokinetic (PK) parameters. We aimed to build a population PK model for cefazolin in critically ill children in order to optimize individual dosing regimens. METHODS: We included all children (age < 18 years, body weight (BW) > 2.5 kg) receiving cefazolin for MSSA infection. Cefazolin total plasma concentrations were quantified by high-performance liquid chromatography. A data modelling process was performed with the software MONOLIX. Monte Carlo simulations were used in order to attain the PK target of 100% fT > 4 ×MIC. RESULTS: Thirty-nine patients with a median (range) age of 7 (0.1-17) years and a BW of 21 (2.8-79) kg were included. The PK was ascribed to a one-compartment model, where typical clearance and volume of distribution estimations were 1.4 L/h and 3.3 L respectively. BW, according to the allometric rules, and estimated glomerular filtration rate (eGFR) on clearance were the two influential covariates. Continuous infusion with a dosing of 100 mg/kg/day to increase to 150 mg/kg/day for children with a BW < 10 kg or eGFR >200 mL/min/1.73m2 were the best schemes to reach the PK target of 100% fT> 4 ×MIC. CONCLUSIONS: In critically ill children infected with MSSA, continuous infusion seems to be the most appropriate scheme to reach the PK target of 100 % fT > 4 ×MIC in children with normal and augmented renal function.

Cervical stitch (cerclage) in combination with other treatments for preventing spontaneous preterm birth in singleton pregnancies.

BACKGROUND: Preterm birth (PTB) remains the foremost global cause of perinatal morbidity and mortality. Thus, the prevention of spontaneous PTB still remains of critical importance. In an attempt to prevent PTB in singleton pregnancies, cervical cerclage, in combination with other treatments, has been advocated. This is because, cervical cerclage is an intervention that is commonly recommended in women with a short cervix at high risk of preterm birth but, despite this, many women still deliver prematurely, as the biological mechanism is incompletely understood. Additionally, previous Cochrane Reviews have been published on the effectiveness of cervical cerclage in singleton and multiple pregnancies, however, none has evaluated the effectiveness of using cervical cerclage in combination with other treatments. OBJECTIVES: To assess whether antibiotics administration, vaginal pessary, reinforcing or second cerclage placement, tocolytic, progesterone, or other interventions at the time of cervical cerclage placement prolong singleton gestation in women at high risk of pregnancy loss based on prior history and/or ultrasound finding of 'short cervix' and/or physical examination. History-indicated cerclage is defined as a cerclage placed usually between 12 and 15 weeks gestation based solely on poor prior obstetrical history, e.g. multiple second trimester losses due to painless dilatation. Ultrasound-indicated cerclage is defined as a cerclage placed usually between 16 and 23 weeks gestation for transvaginal ultrasound cervical length < 20 mm in a woman without cervical dilatation. Physical exam-indicated cerclage is defined as a cerclage placed usually between 16 and 23 weeks gestation because of cervical dilatation of one or more centimetres detected on physical (manual) examination. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (26 September 2019), and reference lists of retrieved studies. SELECTION CRITERIA: We included published, unpublished or ongoing randomised controlled trial (RCTs). Studies using a cluster-RCT design were also eligible for inclusion in this review but none were identified. We excluded quasi-RCTs (e.g. those randomised by date of birth or hospital number) and studies using a cross-over design. We also excluded studies that specified addition of the combination therapy after cervical cerclage because the woman subsequently became symptomatic. We included studies comparing cervical cerclage in combination with one, two or more interventions with cervical cerclage alone in singleton pregnancies. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts of all retrieved articles, selected studies for inclusion, extracted data, assessed risk of bias, and evaluated the certainty of the evidence for this review's main outcomes. Data were checked for accuracy. Standard Cochrane review methods were used throughout. MAIN RESULTS: We identified two studies (involving a total of 73 women) comparing cervical cerclage alone to a different comparator. We also identified three ongoing studies (one investigating vaginal progesterone after cerclage, and two investigating cerclage plus pessary). One study (20 women), conducted in the UK, comparing cervical cerclage in combination with a tocolytic (salbutamol) with cervical cerclage alone in women with singleton pregnancy did not provide any useable data for this review. The other study (involving 53 women, with data from 50 women) took place in the USA and compared cervical cerclage in combination with a tocolytic (indomethacin) and antibiotics (cefazolin or clindamycin) versus cervical cerclage alone - this study did provide useable data for this review (and the study authors also provided additional data on request) but meta-analyses were not possible. This study was generally at a low risk of bias, apart from issues relating to blinding. We downgraded the certainty of evidence for serious risk of bias and imprecision (few participants, few events and wide 95% confidence intervals). Cervical cerclage in combination with an antibiotic and tocolytic versus cervical cerclage alone (one study, 50 women/babies) We are unclear about the effect of cervical cerclage in combination with antibiotics and a tocolytic compared with cervical cerclage alone on the risk of serious neonatal morbidity (RR 0.62, 95% CI 0.31 to 1.24; very low-certainty evidence); perinatal loss (data for miscarriage and stillbirth only - data not available for neonatal death) (RR 0.46, 95% CI 0.13 to 1.64; very low-certainty evidence) or preterm birth < 34 completed weeks of pregnancy (RR 0.78, 95% CI 0.44 to 1.40; very low-certainty evidence). There were no stillbirths (intrauterine death at 24 or more weeks). The trial authors did not report on the numbers of babies discharged home healthy (without obvious pathology) or on the risk of neonatal death. AUTHORS' CONCLUSIONS: Currently, there is insufficient evidence to evaluate the effect of combining a tocolytic (indomethacin) and antibiotics (cefazolin/clindamycin) with cervical cerclage compared with cervical cerclage alone for preventing spontaneous PTB in women with singleton pregnancies. Future studies should recruit sufficient numbers of women to provide meaningful results and should measure neonatal death and numbers of babies discharged home healthy, as well as other important outcomes listed in this review. We did not identify any studies looking at other treatments in combination with cervical cerclage. Future research needs to focus on the role of other interventions such as vaginal support pessary, reinforcing or second cervical cerclage placement, 17-alpha-hydroxyprogesterone caproate or dydrogesterone or vaginal micronised progesterone, omega-3 long chain polyunsaturated fatty acid supplementation and bed rest.

Reanalysis of cefazolin surrogate susceptibility breakpoints utilized as guidances for oral cephalosporin treatments of uncomplicated urinary tract infections: caution concerning application to cefadroxil.

Based on antimicrobial susceptibility test interpretive breakpoint criteria from Clinical and Laboratory Standards Institute and United States Committee on Antimicrobial Susceptibility Testing, cefazolin uncomplicated urinary tract infection (uUTI) surrogate breakpoints do not accurately predict cefadroxil or cephradine susceptibility when testing indicated Enterobacteriaceae species isolates. Hence, these two orally-administered cephalosporins (OC) are not equivalent spectrum substitutes for cephalexin or six other related OC agents for contemporary uUTI therapy.

Comparison of antimicrobial susceptibilities of bacterial isolates between cured and uncured cases of bovine mastitis.

To evaluate the effect of antimicrobial susceptibility on outcomes, we compared the minimum inhibitory concentrations (MICs) for Staphylococcus, Streptococcus, and the family Enterobacteriaceae from cured and uncured mastitis cases; milk shipment for uncured cases could not be resumed within 3 weeks after initial clinical examination. A higher MIC50 of ampicillin and a higher MIC90 of cefazolin for Enterobacteriaceae isolates were observed for cured rather than uncured cases with differences in ≥2 tubes. Endotoxins are generally released from Enterobacteriaceae upon antimicrobial treatment; their amounts are presumed to be greater in mastitis cases resulting from ß-lactam antibiotic-susceptible rather than -resistant microbes. For staphylococcal and streptococcal isolates, the MIC50 and MIC90 of ß-lactam antibiotics were similar for cured and uncured cases.

Methicillin-Resistant Staphylococcus aureus Keratitis: Initial Treatment, Risk Factors, Clinical Features, and Treatment Outcomes.

PURPOSE: To analyze the clinical characteristics, management choices, and outcomes of cases of methicillin-resistant Staphylococcus aureus (MRSA) keratitis. DESIGN: Retrospective interventional case series. METHODS: Fifty-two culture-proven (52 eyes) cases of MRSA keratitis diagnosed and treated at the University of Pittsburgh Medical Center were identified and reviewed. RESULTS: The mean age was 66.6 ± 19.2 years with a median follow-up time of 147 days. The most prevalent risk factors included a history of ocular surgery (62.5%), topical corticosteroid use (35.4%), and dry eye syndrome (37.5%). There was a high burden of systemic disease (95.8%). The average presenting logarithm of minimal angle of resolution visual acuity was 1.7 ± 0.8 and the average final logarithm of minimal angle of resolution visual acuity was 1.2 + 1.0. Initial antibiotic treatment varied, with 20.8% receiving moxifloxacin alone, 20.8% receiving fortified cefazolin and fortified tobramycin together, and 12.5% receiving fortified vancomycin and fortified tobramycin, although other antibiotics were used during treatment if warranted. Surgical management was often required as 17.3% of eyes perforated: 13.5% required tarsorrhaphy, 5.8% required penetrating keratoplasty, and 1 eye was enucleated. When patients treated with fourth-generation fluoroquinolones were compared with those treated with fortified vancomycin, no difference in final visual acuity, treatment duration, or need for surgery was found. CONCLUSION: MRSA causes fulminant keratitis often requiring surgical management with poor visual acuity outcomes. Poor ocular surface, topical corticosteroid use, previous ocular surgery, and/or a high burden of systemic disease were identified as common risk factors. Patients treated with fluoroquinolones in our study had comparable outcomes to those treated with fortified vancomycin; however, those treated with fortified vancomycin tended to have more severe ulcers at presentation.

Comparison of single- and multiple-dose cefazolin as prophylaxis for transurethral enucleation of prostate: A multicenter, prospective, randomized controlled trial by the Japanese Research Group for Urinary Tract Infection.

OBJECTIVES: To compare the optimal administration period of antimicrobial prophylaxis in patients undergoing transurethral enucleation of the prostate for benign prostatic hyperplasia. METHODS: We carried out a randomized controlled trial to compare the differences in incidence of perioperative genitourinary tract infection between single and multiple (3 days) administrations of cefazolin for transurethral enucleation of the prostate in benign prostatic hyperplasia patients without pyuria or bacteriuria between January 2015 and December 2018. RESULTS: This multicenter randomized controlled trial included 203 patients who underwent a transurethral enucleation of the prostate procedure. All received antimicrobial prophylaxis, and were randomized into those who received single-dose (n = 101) or multiple-dose (n = 102) therapy. The rate of genitourinary tract infection after transurethral enucleation of the prostate for all patients was 1.5%, whereas that in the single-dose group was 1.0% and in the multiple-dose group was 2.0%, which were not significantly different (P = 1.00). CONCLUSIONS: A single dose of antimicrobial prophylaxis as a prophylactic antibacterial drug is sufficient for patients undergoing transurethral enucleation of the prostate who do not have presurgical pyuria or bacteriuria.

Optimization of the empirical antibiotic choice during the treatment of acute prosthetic joint infections: a retrospective analysis of 91 patients.

Background and purpose - The preferred treatment of an acute prosthetic joint infection (PJI) is debridement, antibiotics, irrigation and retention of the prosthesis (DAIR). The antibiotic treatment consists of an empirical and targeted phase. In the empirical phase, intravenous antibiotics are started after surgery before micro-organisms are determined in microbiological cultures. Which empirical antibiotic is used differs between hospitals, partly reflecting geographic differences in susceptibility spectrums. We investigated whether flucloxacillin should remain the antibiotic of choice in our hospital for empiric treatment of acute PJI with DAIR. Patients and methods - We retrospectively analyzed 91 patients treated for PJI with DAIR between 2012 and 2016. The susceptibility of micro-organisms was determined in multiple cultures of periprosthetic tissue and synovial fluid for 3 antibiotics: amoxicillin/clavulanic acid, cefazolin, and flucloxacillin. Results - Positive microbiological cultures from 68 patients were analyzed. Staphylococcus aureus was the predominant pathogen, cultured in half of the patients. In one-third of patients more than 1 micro-organism was found. On a patient level, the data showed that 65% were responsive to flucloxacillin, 76% to amoxicillin/clavulanic acid, and 79% to cefazolin. Interpretation - Flucloxacillin appeared to be a suboptimal choice in our patient population treated with DAIR. We therefore changed our practice to cefazolin as the preferred antibiotic in the empirical treatment of acute PJI with DAIR.

The pathogen spectrum and resistance in patients with peritoneal dialysis-associated peritonitis: A single-center, observational clinical study
.

BACKGROUND: Peritoneal dialysis-associated peritonitis (PDAP) is one of the major causes of peritoneal dialysis (PD) failure and death. Therefore, it is important to determine how to effectively treat patients with PDAP. MATERIALS AND METHODS: We analyzed the pathogen spectrum and bacterial resistance in 203 PDAP cases that were enrolled in this study from January 1, 2015 to December 31, 2017. All patients were infected with peritonitis and had been treated with antibiotics while at our center. Bacterial culture results of PD fluid and pathogen drug resistance were collected and analyzed. A total of 159 cases (78.3%) had a positive bacterial culture of PD fluid. RESULTS: A total of 47 pathogens were identified, including 19 (40.4%) Gram-positive cocci strains (the most common was Staphylococcus spp.), 15 (31.9%) Gram-negative bacilli strains (the most common was Escherichia coli, 4 fungal strains, and 9 other strains. The drug sensitivity test showed that Gram-positive cocci were sensitive to vancomycin (94.9%), but had a high resistance to cefazolin (67.7%). Gram-negative bacilli were sensitive to imipenem (96.2%), but had a high resistance to ceftriaxone (60.0%). Voriconazole and itraconazole were sensitive in fungal infections. A total of 162 cases were cured, 37 cases were unresponsive to antibiotic treatment and converted to hemodialysis after Tenckhoff catheter removal, and 4 cases resulted in death. CONCLUSION: Gram-positive cocci are still the primary pathogen of PDAP cases in our center, but demonstrate a high resistance to first-generation cephalosporin, which is the suggested treatment per International Society for Peritoneal Dialysis 2016 Peritonitis Recommendations. Therefore, an individualized treatment based on the distribution of pathogens and drug resistance in different centers is more conducive to improve the cure rate of PDAP.

High-Dosage Cefazolin Achieves Sufficient Cerebrospinal Diffusion To Treat an External Ventricular Drainage-Related Staphylococcus aureus Ventriculitis.

A patient received continuous infusion of cefazolin 10 g then 8 g daily for an external ventricular drainage-related methicillin-susceptible Staphylococcus aureus (MSSA) ventriculitis. Median free concentrations in the cerebrospinal fluid were 11.9 and 6.1 mg/liter after 10- and 8-g doses, respectively. Free concentrations in the cerebrospinal fluid were always above the MIC usually displayed by methicillin-susceptible Staphylococcus aureus (MSSA) isolates. These results support the use of high-dose cefazolin to achieve sufficient meningeal concentrations.

Formulation development and characterization of cefazolin nanoparticles-loaded cross-linked films of sodium alginate and pectin as wound dressings.

The present study focuses on the preparation of nanoparticles-loaded ionic cross-linked films for the topical delivery of cefazolin. The aim of the study was to prepare a dosage form which can provide local effect of cefazolin along with sustained delivery at the site of application. Cefazolin was loaded into chitosan nanoparticles to mask the burst release of the drug and they were optimized based on particle size, PDI, % EE and zeta potential. Finally, the prepared nanoparticles were loaded into the films comprising of sodium alginate and pectin which were then subjected to cross-linking via calcium chloride to improve the mechanical strength of the hydrogel films upon exposure to wound fluid. The films were assessed for physical and mechanical properties, swelling behavior, water transmission rate, mucoadhesion, FTIR, DSC, percent inhibition assay and in vitro release profile. Optimized formulation with Cefazolin nanoparticles in the size range of 227 nm and 0.5% CL films showed significantly better results (p < 0.05) as compared to the films with increased cross-linker concentration. Therefore, 0.5% CL films were considered more suitable for the treatment of infections when applied as wound dressing.

Comparison of 2 Perioperative Management Protocols and Their Influence on Postoperative Recovery after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Standard Parenteral Nutrition, Selective Bowel Decontamination and Suprapubic Catheters?

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is associated with considerable postoperative morbidity, including ileus and infectious complications. Perioperative care is believed to be an important factor for the development and treatment of postoperative morbidity. PATIENTS AND METHODS: Data on case-matched patients from a retrospective database of 2 Dutch HIPEC centres was compared. Patient selection and procedures were identical in both hospitals although perioperative management items differ slightly. In centre B, immediate total parenteral nutrition (TPN), suprapubic urine bladder catheter placement (SPCs) and selective decontamination of the digestive-tract are standard care for CRS-HIPEC patients, while in centre A, they are not. RESULTS: From a total of 223 patients, 68 consecutive patients from centre B were compared to 68 matched patients from centre A. TPN was administered to 54.4% of patients in centre A because of prolonged ileus, whereas it was standard of care in centre B. In all, 105 (77.2%) patients experienced postoperative complications including 17.6% who had a grades III-IV complication. The incidence of grade III-V complications was 18 (26.4%) in centre A and 8 (11.8%) in centre B (p = 0.03). Median hospital stay was 12 days (7-84) in A and 11(6-80) in centre B (p = 0.546). CONCLUSIONS: Gastrointestinal recovery after CRS-HIPEC seems to take longer as compared to other surgical procedures. Between the 2 centres, a significant difference in severe complications was found, while standard TPN, selective bowel decontamination and SPCs were the only identified differences in perioperative care.

Prevalence of a Cefazolin Inoculum Effect Associated with blaZ Gene Types among Methicillin-Susceptible Staphylococcus aureus Isolates from Four Major Medical Centers in Chicago.

The efficacy of cefazolin with high-inoculum methicillin-susceptible Staphylococcus aureus (MSSA) infections remains in question due to therapeutic failure inferred as being due to an inoculum effect (InE). This study investigated the local prevalence of a cefazolin InE (CInE) and its association with staphylococcal blaZ gene types among MSSA isolates in the Chicago area. Four medical centers in Chicago, IL, contributed MSSA isolates. Cefazolin MICs (C-MIC) were determined at 24 h by the broth microdilution method using a standard inoculum (SI; 5 × 105 CFU/ml) and a high inoculum (HI; 5 × 107 CFU/ml). The CInE was defined as (i) a ≥4-fold increase in C-MIC between SI and HI and/or (ii) a pronounced CInE, i.e., a nonsusceptible C-MIC of ≥16 µg/ml at HI. PCR was used to amplify the blaZ gene, followed by agarose gel electrophoresis and sequencing to determine the gene type. Approximately 269 MSSA isolates were included. All but one isolate were susceptible to cefazolin at SI, and 97% remained susceptible at HI. A total of 196 isolates (73%) were blaZ positive, with the blaZ types led by gene type C (40%). CInE was seen in 45 blaZ-positive isolates (23%), with 44 (22%) presenting a ≥4-fold increase in C-MIC (SI to HI) and 5 (3%) a pronounced CInE. Four of the five met both definitions of CInE, two of which expressed the type A gene. The prevalence of a pronounced CInE associated with the type A blaZ gene from MSSA isolates in Chicago is low. Our predilection for cefazolin use, even early in the management of hospitalized MSSA infections, is tenable.

Hypoprothrombinemia and severe perioperative haemorrhagic complications in cardiac surgery patients treated with high-dose cefazolin for infective endocarditis.

Endocarditis is a serious and common disease that requires prolonged antimicrobial therapy. The recent shortage of oxacillin has led to the use of other antimicrobial agents such as cefazolin to treat endocarditis due to methicillin-sensitive Staphylococcus aureus. We describe four cases of life-threatening haemorrhagic complications (fatal in two cases) in patients treated with high-dose cefazolin. All of these patients with major bleeding presented with hypoprothrombinemia secondary to hypovitaminosis K. This adverse event may be due to inhibition of vitamin K epoxide reductase and/or gamma-glutamyl-carboxylase by the 2-methyl-1,2,3-thiadiazol-5-thiol group of cefazolin. This inhibition may result in hypoprothrombinemia by altering the synthesis of vitamin K-dependent coagulation factors. The increasing use of cefazolin, especially at a high dose and for a prolonged period of time, should be accompanied by regular monitoring of coagulation, including prothrombin index, and vitamin K supplementation.

Empiric antibiotic protocols for cancer patients with neutropenia: a single-center study of treatment efficacy and mortality in patients with bacteremia.

BACKGROUND: There are several empiric antibiotic treatment options for febrile neutropenia, yet there is no universally-accepted initial protocol. We aimed to assess the performance of a protocol (piperacillin, gentamicin and cefazolin) introduced over 40 years ago and compare its coverage against bacteria isolated from blood of neutropenic patients with that of various commonly used antibiotic treatment protocols. METHODS: Adults with neutropenia admitted between 2003 and 2012 to the hemato-oncologic departments and in whom blood cultures were taken on admission were included. Appropriateness of several common antibiotic protocols was assessed based on the susceptibility of the blood isolates. Crude mortality rates were computed by the susceptibility of bacteria isolated from patients' blood to the actual treatment given. RESULTS: In total, 180 admissions of neutropenic patients (95 in patients who had fever above 38 °C) with positive blood cultures were analyzed. The actual antibiotic regimen prescribed was deemed appropriate in 82% of bacteremia episodes. The recommended institutional protocol was used in 62% of bacteremia episodes in neutropenic patients. This protocol would have been appropriate in 85% of all neutropenic bacteremia episodes and 89% of episodes in febrile neutropenia patients compared with piperacillin/tazobactam (79%, P = 0.13 and 76%, P = 0.002, respectively) and imipenem (93%, P = 0.004 and 92%, P = 0.74, respectively). Isolation of bacteria resistant to the actual antibiotic treatment given was associated with higher mortality at one week and at 30 days. CONCLUSION: Common current antibiotic regimens provide similar coverage among febrile neutropenic patients, whereas broad spectrum antibiotic combinations maximize coverage among neutropenic patients.

Effect of the 2014 Clinical and Laboratory Standards Institute urine-specific breakpoints on cefazolin susceptibility rates at a community teaching hospital.

BACKGROUND: Enterobacteriaceae, which include Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, are identified as the infectious etiology in the majority of urinary tract infections (UTIs) in community hospitals across the United States. The minimum inhibitory concentration (MIC) is a useful tool when choosing an appropriate antibacterial agent. Recent changes to the 2014 Clinical and Laboratory Standards Institute (CLSI) guidelines included reporting a urine-specific cefazolin breakpoint for enterobacteriaceae (susceptible ≤16 mcg/mL). The purpose of this study was to determine the clinical and financial impact of implementing the 2014 CLSI urine-specific breakpoints for cefazolin in a community-based teaching hospital in the Southern U.S.A. METHODS: A retrospective review of patients hospitalized from January 1, 2010 through October 1, 2014 was performed. Patients that met inclusion criteria had a documented initial clinical isolate of E. coli, K. pneumoniae, or P. mirabilis from urine cultures during each year. Descriptive statistics and two-proportion test of hypothesis were used in the analysis to compare susceptibility rates before and after implementation of the updated CLSI breakpoints for cefazolin. RESULTS: A total of 190 clinical isolates from patients were included in the study. E. coli was the most common organism isolated (63.7%), followed by K. pneumoniae (22.1%), and P. mirabilis (14.2%). 86% of the included isolates were susceptible to cefazolin using the 2010 breakpoints. Implementation of the 2014 breakpoints did not significantly impact susceptibility results for E. coli, K. pneumoniae, or P. mirabilis. CONCLUSION: Modification of breakpoints did not significantly impact susceptibility rates of cefazolin. Substituting cefazolin may decrease the overall drug cost by 77.5%. More data is needed to correlate in vitro findings with clinical outcomes using cefazolin for UTIs.

Antibiotics in acute calculous cholecystitis - do Tokyo guidelines influence the surgeons' practices?

OBJECTIVE: To observe changes in surgeons' practice of antibiotic usage in patients with acute cholecystitis before and after the implementation of Tokyo Guidelines. METHODS: This retrospective, descriptive study was conducted at the Aga Khan University Hospital, Karachi, and comprised the medical records of all patients with the diagnosis of acute calculus cholecystitis who presented in 2009 and those who presented in 2014 after the implementation of Tokyo Guidelines. The major variables included patients' demographics, antibiotics used and surgical outcomes. SPSS 19 was used for data analysis. RESULTS: Of the 356 patients, 96(27%) were treated in 2009 and 260(73%) in 2014. The overall mean age was 48.9±14 years. There were 185(52%) females and 171(48%) males. Comparison of the data from 2 years showed no difference in gender, American Society of Anaesthesiologists level, grade of acute cholecystitis and frequency of use of empiric antibiotics (p>0.05 each). However, there was significantly less use of combination therapy (p=0.00) and metronidazole (p=0.00) in 2014than in 2009. Interval cholecystectomy was significantly less practised in 2014 (p=0.03) resulting in shorter hospital stay (p=0.00). Despite improvement in antibiotic usage practices, post-operative infection rates remained the same in both the groups (p=0.58). CONCLUSIONS: Implementation of Tokyo Guidelines not only greatly influenced but also standardised the choice of antibiotics in patients without compromising the infective and surgical outcomes.

Efficacy of Ceftaroline against Methicillin-Susceptible Staphylococcus aureus Exhibiting the Cefazolin High-Inoculum Effect in a Rat Model of Endocarditis.

Certain Staphylococcus aureus strains exhibit an inoculum effect (InE) with cefazolin (CFZ) that has been associated with therapeutic failures in high-inoculum infections. We assessed the in vitro activities of ceftaroline (CPT), CFZ, and nafcillin (NAF) against 17 type A ß-lactamase (ßla)-producing, methicillin-susceptible S. aureus (MSSA) strains, including the previously reported TX0117, which exhibits the CFZ InE, and its ßla-cured derivative, TX0117c. Additionally, we determined the pharmacokinetics of CPT in rats after single intramuscular doses of 20 and 40 mg/kg of body weight and evaluated the activities of CPT (40 mg/kg every 8 h [q8h]), CFZ, and NAF against TX0117 and TX0117c in a rat model of infective endocarditis. No InE was observed for CPT or NAF, whereas a marked InE was detected for CFZ (MIC, 8 to ≥128 µg/ml). CPT and NAF treatment against TX0117 resulted in mean bacterial counts of 2.3 and 2.1 log10 CFU/g in vegetations, respectively, compared to a mean of 5.9 log10 CFU/g in the CFZ-treated group (CPT and NAF versus CFZ, P = 0.001; CPT versus NAF, P = 0.9830). Both CFZ and CPT were efficacious against the ßla-cured derivative, TX0117c, compared to time zero (t0) (P = <0.0001 and 0.0015, respectively). Our data reiterate the in vivo consequences of the CFZ InE and show that CPT is not affected by this phenomenon. CPT might be considered for high-inoculum infections caused by MSSA exhibiting the CFZ InE.