Information on the physical compatibility of intravenous (IV) medications is vital for patient care and safety in acute care settings. Drug information resources list ondansetron and nafcillin as IV compatible, however, bolus concentrations of ondansetron are not reported. This study investigated the in vitro physical compatibility of bolus and infusion concentrations of ondansetron hydrochloride with nafcillin sodium. Two admixtures were prepared: 1) ondansetron hydrochloride 2 mg/mL and nafcillin sodium 20 mg/mL, and 2) ondansetron hydrochloride 0.16 mg/mL and nafcillin sodium 20 mg/mL. The admixtures were prepared in triplicate using aseptic technique according to manufacturer guidance and stored at room temperature (22-23 °C) for up to 24 hours. Admixtures were examined for visual precipitation, turbidity, and pH at baseline and at 1, 5, 8, and 24 hours. Admixture 1 developed a haze immediately after mixing, which was sustained over 24 hours. There was a demonstrative change in absorbance after 1 hour, but pH remained stable until hour 24. Admixture 2 developed a haze at 5 hours, but the absorbance and pH remained stable until hour 24; a decrease in the pH was observed in all samples at hour 24. This in vitro study revealed that ondansetron hydrochloride 2 mg/mL and nafcillin sodium 20 mg/mL are not physically compatible when administered through the same IV line. No demonstrative change was observed with ondansetron hydrochloride 0.16 mg/mL and nafcillin sodium 20 mg/mL; however, concurrent administration of these medications is questionable when delivered through an IV line for periods of five hours or longer.

BACKGROUND: Maximal skin testing (ST) nonirritant concentrations (NICs) are consistent for penicillin and aminopenicillin amongst guidelines. However, there is variability amongst guidelines for maximal ST NICs of cephalosporins.
OBJECTIVE: To determine maximal immediate and delayed ST NICs of 15 β-lactams in β-lactam-tolerant and β-lactam-naïve participants.
METHODS: We performed a single-center, nonrandomized prospective study between September 2019 and January 2022 in adult participants. Participants received skin prick testing (SPT) and intradermal test (IDT) injections at six increasing concentrations of 1 or more β-lactams. A concentration was considered irritant when more than 5% of participants had a positive test. A positive test was defined as a wheal ≥3 mm than negative control accompanied by a ≥5 mm flare for SPT/IDT and induration ≥5 mm with associated erythema at 48 hours for delayed readings (dIDT). Sensitivity analyses using 3 alternative IDT positive criteria were conducted.
RESULTS: A total of 747 participants with a median age of 64 (IQR 54-72), 52% males, 85% White, and 92% Non-Hispanic underwent 20,858 skin tests. All undiluted SPT concentrations were nonirritant. We found the following maximal IDT/dIDT NICs (mg/ml): ampicillin (41.6/125), ampicillin-sulbactam (93.8/187.5), aztreonam (6.3/25), cefazolin (55/165), cefepime (35/140), cefoxitin (45/90), ceftaroline (7.5/15), ceftriaxone (58.3/175), cefuroxime (55/110), ertapenem (16.6/50), imipenem-cilastin (6.3/25), meropenem (8.3/25), nafcillin (31.3/62.5), oxacillin (20.9/83.5), and piperacillin-tazobactam (112.5/225). dIDTs were almost all completely non-irritant close or at undiluted concentrations. There were no differences when we applied 3 IDT positivity criteria to our raw data.
CONCLUSIONS: Our results suggest that SPTs with undiluted stock β-lactam antibiotic concentrations are nonirritant. Compared to previously published nonirritant concentrations, we propose a 2 to 50-fold increase to the maximal IDT and dIDT NICs of 15 β-lactam antibiotics. When performing dIDTs, a higher concentration should be used rather than the same IDT concentration.

Methicillin-resistant Staphylococcus aureus (MRSA) infections are often difficult to treat because of their biofilm-forming ability and antimicrobial resistance. We investigated the effects of sub-minimal inhibitory concentrations (MICs) of antibiotics on MRSA biofilm formation. Clinical MRSA isolates were grown with sub-MICs (1/256-1/2 × MICs) of nafcillin, vancomycin, ciprofloxacin, and rifampin. The biofilm biomass was measured using crystal violet staining. Of the 107 MRSA isolates tested, 63 (58.9%) belonged to sequence type 5 (ST5), and 44 (41.1%) belonged to ST72. The MIC50/MIC90 values of nafcillin, vancomycin, ciprofloxacin, and rifampin were 256/512, 1/2, 64/512, and 0.008/0.03 mg/L, respectively. The sub-MICs of nafcillin, vancomycin, ciprofloxacin, and rifampin promoted biofilm formation in 75 (70.1%), 49 (45.8%), 89 (83.2%), and 89 (83.2%) isolates, respectively. At sub-MICs of nafcillin, the factors associated with strong biofilm induction were the ST5 strain (P = 0.001) and agr dysfunction (P = 0.005). For the sub-MICs of ciprofloxacin, the associated factors were the ST5 strain (P = 0.002), staphylococcal protein A type t002 strain (P < 0.001), and ciprofloxacin resistance (P < 0.001). Among the sub-MICs of rifampin, only ST5 was associated with strong biofilm induction (P = 0.006). Because the sub-MICs of rifampin were much lower than clinically relevant concentrations, we further tested the capability of biofilm induction in 0.03[Formula: see text]32 mg/L of rifampin. At these concentrations, rifampin-induced biofilm formation was rare in rifampin-susceptible MRSA [1.0% (1 of 100)] but common in rifampin-resistant MRSA [71.4% (5 of 7), P < 0.001]. Induction of biofilm biomass at sub-MICs of antibiotics is common in clinical MRSA isolates and is differentially affected by the MRSA strain and antibiotic class.
OBJECTIVE: Bacteria can be exposed to sub-MICs of antibiotics at the beginning and end of a dosing regimen, between doses, or during low-dose therapies. Growing evidence suggests that sub-MICs of antimicrobials can stimulate MRSA biofilm formation and alter the composition of the biofilm matrix. Pevious studies have found that sub-MICs of oxacillin, methicillin, and amoxicillin promote biofilm formation in some community-acquired MRSA (CA-MRSA). We evaluated biofilm induction by sub-MICs of four different classes of antibiotics in 44 CA-MRSA and 63 healthcare-associated MRSA (HA-MRSA) strains. Our study indicated that sub-MICs of nafcillin, vancomycin, ciprofloxacin, and rifampin frequently promote biofilm induction in clinical MRSA isolates. Strong biofilm induction in sub-MICs of nafcillin, ciprofloxacin, and rifampin was more frequent in HA-MRSA than in CA-MRSA. Antibiotic-induced biofilm formation depends on the antibiotic class, MRSA strain, and antibiotic resistance. Our results emphasize the importance of maintaining effective bactericidal concentrations of antibiotics to treat biofilm-related infections.

We evaluated the role of Staphylococcus aureus AbcA transporter in bacterial persistence and survival following exposure to the bactericidal agents nafcillin and oxacillin at both the population and single-cell levels. We show that AbcA overexpression resulted in resistance to nafcillin but not oxacillin. Using distinct fluorescent reporters of cell viability and AbcA expression, we found that over 6-14 hours of persistence formation, the proportion of AbcA reporter-expressing cells assessed by confocal microscopy increased sixfold as cell viability reporters decreased. Similarly, single-cell analysis in a high-throughput microfluidic system found a strong correspondence between antibiotic exposure and AbcA reporter expression. Persister cells grown in the absence of antibiotics showed neither an increase in nafcillin MIC nor in abcA transcript levels, indicating that survival was not associated with stable mutational resistance or abcA overexpression. Furthermore, persister cell levels on exposure to 1×MIC and 25×MIC of nafcillin decreased in an abcA knockout mutant. Survivors of nafcillin and oxacillin treatment overexpressed transporter AbcA, contributing to an enrichment of the number of persisters during treatment with pump-substrate nafcillin but not with pump-non-substrate oxacillin, indicating that efflux pump expression can contribute selectively to the survival of a persister population.

After craniectomy, autologous bone flaps may be stored using wet or dry cryopreservation. After brain edema subsides, they are replaced during an operation termed cranioplasty. Cranioplasty is associated with 15% infection incidence.
We conducted a retrospective comparison of infection outcomes between wet and dry cryopreservation of cranioplasty bone flaps. Historically, bone flaps were stored utilizing wet cryopreservation-bone flap storage in 1 L of lactated Ringer\'s solution containing 80 mg gentamicin and 2 g nafcillin in a sterile plastic container secured in an unsterile plastic bag. Our newer dry cryopreservation protocol involved storage in gauze soaked in 80 mg gentamicin and 2 g nafcillin within a 3-layer sterile bag system.
A total of 119 autologous bone flaps were included, with median follow-up of 3.9 months from cranioplasty. Overall, 10.9% became infected, requiring subsequent surgery; 18.4% of 49 bone flaps stored using wet cryopreservation became infected compared with only 5.7% of 70 dry cryopreservation bone flaps (P = 0.038; relative risk [RR] 0.311; absolute risk reduction 12.7%). Tobacco use (P = 0.076; RR 3.17) was not associated with increased infection risk. Infection incidence was similar for traumatic craniectomy indications compared to the other indications (12.0% trauma vs. 10.1% other; P = 0.750). On average, infected cranioplasty patients spent 8.5 more days hospitalized and faced increased risk of additional complications.
Dry cryopreservation significantly decreases infection after cranioplasty when compared with wet cryopreservation, and this mitigates additional morbidity, mortality, and costs attributable to cranioplasty infection. Other nonmodifiable risk factors for cranioplasty infection were identified.

In this study, iron oxide nanoparticles were synthesized from Solanum nigrum L. extract and used to remove nafcillin, which exhibits toxic properties in aqueous solutions. To understand the adsorption behavior of naphcillin on the nanoadsorbent, the optimum conditions, kinetics and isotherm of adsorption were studied in detail. It was found that the adsorption process was consistent with the pseudo-second order kinetic model and Langmuir\'s isothermal model. The FeONPs adsorbent achieved an adsorption capacity of 116.3 mg/g for nafcillin. It was also found that FeONPs retained ~90% of its adsorption capacity after five adsorption-desorption cycles. Apart from the fact that the nanoparticles synthesized in the study are composed of natural ingredients, S. nigrum L. which causes problems in plant cultivation, serves a useful purpose by being used in this method. The results show that this new nanoadsorbent provides an alternative option for the removal of pharmaceuticals and various pollutants in wastewater.

In this study, novel materials have been obtained via a dual covalent and ionic crosslinking strategies, leading to the formation of a fully interpenetrated polymeric network with remarkable mechanical performances as drug delivery platforms for dermal patches. The polymeric network was obtained by the free-radical photopolymerization of N-vinylpyrrolidone using tri(ethylene glycol) divinyl ether as crosslinker in the presence of sodium alginate (1%, weight%). The ionic crosslinking was achieved by the addition of Zn2+, ions which were coordinated by the alginate chains. Bentonite nanoclay was incorporated in hydrogel formulations to capitalize on its mechanical reinforcement and adsorptive capacity. TiO2 and ZnO nanoparticles were also included in two of the samples to evaluate their influence on the morphology, mechanical properties and/or the antimicrobial activity of the hydrogels. The double-crosslinked nanocomposite hydrogels presented a good tensile resistance (1.5 MPa at 70% strain) and compression resistance (12.5 MPa at a strain of 70%). Nafcillin was loaded into nanocomposite hydrogel films with a loading efficiency of up to 30%. The drug release characteristics were evaluated, and the profile was fitted by mathematical models that describe the physical processes taking place during the drug transfer from the polymer to a PBS (phosphate-buffered saline) solution. Depending on the design of the polymeric network and the nanofillers included, it was demonstrated that the nafcillin loaded into the nanocomposite hydrogel films ensured a high to moderate activity against S. aureus and S. pyogenes and no activity against E. coli. Furthermore, it was demonstrated that the presence of zinc ions in these polymeric matrices can be correlated with the inactivation of E. coli.

Skin infections are frequently treated via intravenous or oral administration of antibiotics, which can lead to serious adverse effects and may sometimes contribute to the proliferation of resistant bacterial strains. Skin represents a convenient pathway for delivering therapeutic compounds, ensured by the high number of blood vessels and amount of lymphatic fluids in the cutaneous tissues, which are systematically connected to the rest of the body. This study provides a novel, straightforward method to obtain nafcillin-loaded photocrosslinkable nanocomposite hydrogels and demonstrates their performance as drug carriers and antimicrobial efficacy against Gram-positive bacteria. The novel formulations obtained, based on polyvinylpyrrolidone, tri(ethylene glycol) divinyl ether crosslinker, hydrophilic bentonite nanoclay, and/or two types of photoactive (TiO2 and ZnO) nanofillers, were characterized using various analytical methods (transmission electron microscopy (TEM), scanning electron microscopy-energy-dispersive X-ray analysis (SEM-EDX), mechanical tests (tension, compression, and shear), ultraviolet-visible spectroscopy (UV-Vis), swelling investigations, and via specific microbiological assays (\"agar disc diffusion method\" and \"time-kill test\"). The results reveal that the nanocomposite hydrogel possessed high mechanical resistance, good swelling abilities, and good antimicrobial activity, demonstrating a decrease in the bacteria growth between 3log10 and 2log10 after one hour of direct contact with S. aureus.

Antistaphylococcal penicillins (ASP) and cefazolin are first-line treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. Borderline oxacillin resistance (i.e., oxacillin MICs 1-8 μg/mL) is observed in strains hyperproducing beta-lactamases. This mechanism is also behind the proposed inoculum effect. Minimal data exists on the comparative efficacy of cefazolin or ASP in qualitatively susceptible strains that demonstrate MICs of oxacillin of 1 to 2 μg/mL compared to strains with MIC of oxacillin < 1 μg/mL. We performed a retrospective cohort study of acute treatment outcomes in adult patients with community-acquired MSSA bacteremia treated with cefazolin or ASP, stratified by oxacillin MIC. The primary outcome was a composite of all-cause mortality during the index inpatient admission, failure to clear blood cultures within 72 h after initiating definitive therapy, and change in therapy due to perceived lack of efficacy. A total of 402 patients were included in this study, including 226 isolates with an oxacillin MIC ≥ 1 μg/mL and 176 isolates with an MIC < 1 μg/mL. There were no differences in the rate of the primary outcome occurrence between patients with an oxacillin MIC ≥ 1 μg/mL and an MIC < 1 μg/mL (16.4% versus 15.9%, P = 0.90). There was no difference in the primary outcome between high versus low oxacillin MIC groups among those who received ASP (22.9% versus 24.1%, P = 0.86) or cefazolin (10.3% versus 11.9%, P = 0.86). In our cohort of patients with MSSA bacteremia, oxacillin MIC (i.e., ≥ 1 versus < 1 μg/mL) was not associated with acute treatment outcomes, regardless of the beta-lactam selected as definitive therapy.

Methicillin-resistant Staphylococcus epidermidis (MRSE) endocarditis failing conventional therapy has been successfully treated with nafcillin plus daptomycin in the clinic. In vitro studies showed that nafcillin enhanced daptomycin killing of MRSE in both planktonic cells and biofilm. Nafcillin exposure also sensitized MRSE to killing by human neutrophils and cathelicidin antimicrobial peptide LL-37. Fluorescent microscopy showed increased daptomycin and LL-37 binding to the MRSE bacterial surface upon nafcillin treatment. Ceftaroline also increased MRSE killing by daptomycin in planktonic cultures and biofilms, as well as daptomycin and LL-37 binding on the bacterial surface. Nafcillin, ceftaroline, and possibly other β-lactams, may serve an important role in the therapy of MRSE endocarditis through augmentation of cationic peptide, the innate immune system, and daptomycin killing. Clinical studies will be needed to determine how early these regimens should be deployed to optimize clinical outcome.