ObjectiveTo investigate the physical and chemical stability of cefminox sodium, cefuroxime sodium, cefoxitin sodium, ceftizoxime sodium, cefmetazole sodium, ceftazidime and cefamandole nafate when continuously infused with 0.9% sodium chloride (NS) and 5% glucose (GS).MethodsSeven cephalosporin antibiotics were reconstituted in 50 and 100 mL of NS and GS, and stored at room temperature. Samples were collected at 0, 2, 4, 8, and 24 hours to evaluate changes in appearance, pH, insoluble particle count, and drug content.ResultsThe admixture solutions of cefuroxime with both solvents turned yellow at 8 hours. The relative percentage content of the low-concentration group in NS dropped to 82.97% at 24 hours. When cefamandole nafate was admixed with NS, contents of both high and low concentrations dropped below 90% at 8 hours and below 60% at 24 hours. The pH change of the high-concentration group exceeded 1.0 pH unit at 24 hours. For cefoxitin sodium, the pH change of all concentration groups admixed with both solvents exceeded 1.0 pH unit at 24 hours. The high-concentration group in NS declined to 87.72%. The admixture solutions of cefminox with both solvents showed slight discoloration at 24 hours. When cefminox was admixed with GS, the contents of both concentration groups dropped below 90% at 2 hours. All other drug–solvent–concentration combinations had all indicators within the specified limits.ConclusionWhen admixed with NS, cefmetazole, ceftazidime, and ceftizoxime are stable for 24 hours continuous infusion; cefoxitin and cefminox for up to 8 hours; and cefuroxime and cefamandole nafate for 4 hours. When admixed with GS, cefmetazole, ceftazidime, and ceftizoxime are stable for 24 hours; cefoxitin for up to 8 hours; cefuroxime for 4 hours; and cefminox has a stability period of less than 2 hours, so GS is not recommended as it is continuous infusion solvent.

In this research, a novel class of biologically active bimetallic Cu(II) compounds has been discovered as cutting-edge antibiofilm agents with metallo-β-lactamase (MBL) inhibitory activity against the clinically isolated multidrug-resistant (MDR) gram-negative bacterium, Pseudomonas aeruginosa (Pa-CI-1). As the traditional strategies for antibiotic development are proving inadequate against the swift evolution of bacterial resistance, there is an urgent need to establish novel antibacterial strategies with mechanism different from those of prevailing antibiotics. Thus, the 2,6-bis[N-{N-(carboxymethyl)-N-(pyridylmethyl)amine}methyl]-4-methylphenol (H3L)-incorporated three bimetallic Cu(II) compounds, [Cu2L(H2O)(Cl)]·H2O (1), [Cu2L(H2O)(NO3)]·H2O (2) and [Cu2L(H2O)(CH3CO2)]·H2O (3) has been strategically designed and synthesized with an unsymmetrical coordination arrangement that synergistically modifies the electronic environment of Cu centers for the enhancement of antibacterial and antibiofilm activity. The electronic environment of Cu(II) and its adjoining atoms has been further modified by substituting Cl- in 1 by NO3 - in 2 and CH3CO2 - in 3. The standard nitrocefin assay disclosed that 1-3 significantly inhibited the activity of MBLs produced by Pa-CI-1 at the half minimum inhibitory concentration (1/2 MIC). Molecular docking study suggested an excellent propensity of these Cu compounds for binding with MBL-producing proteins such as Verona integron-encoded metallo-β-lactamase (VIM-1), Sao Paulo metallo-β-lactamase (SPM-1), imipenemase (IMP-1), AmpC, and New Delhi metallo-β-lactamase (NDM-1). However, the best possible interaction was observed for VIM-1 protein. All three Cu(II) compounds displayed significantly high antibacterial and antibiofilm activity as established by multiple bioassays, including ex vivo applicability studies. However, 1 and 3 showed an outstanding activity with MIC values of 200 and 150 µg/mL, respectively, in comparison to 2 with an MIC of 300 µg/mL. They showed an exceptional combinatorial activity when examined with five different commercially accessible β-lactam-based antibiotics, such as amoxicillin (AMX), chloramphenicol (CHL), cefotaxime (CTX), ceftriaxone (CTR), and cefoxitin (CX) against Pa-CI-1. It has been suggested that the as-synthesized Cu compounds also blocked the activity of MBLs via strong interactions with the active sites of enzymes, thus restoring the normal activity of the antibiotics. Our study disclosed that 1-3 could be the emergent drug leads and attract great attention to the materials and biological chemists, combating antimicrobial resistance (AMR).

The escalating threat of mycobacterial infectious diseases, particularly those caused by nontuberculous mycobacteria (NTM), poses a serious challenge to public health. Linezolid (LZD), an oxazolidinone antimicrobial, exhibits potent activity against Mycobacterium tuberculosis and NTM. Generally, mutations in the rrl and rplC genes are widely associated with resistance to LZD. However, in this study, we screened Mycobacterium marinum strains lacking such mutations, indicating the presence of an alternative resistance mechanism. Notably, through whole-genome sequencing, we identified a novel mutation C395T in the MMAR_0911 (grcC1) gene that has never been linked to drug resistance. This mutation leads to an A132V substitution in the encoded protein, a polyprenyl diphosphate synthase potentially involved in the synthesis of cell wall components and menaquinones. We found that the overexpression of grcC1 caused resistance to multiple drugs including LZD, clarithromycin (CLR), vancomycin (VAN), clofazimine (CFZ), rifampicin (RIF), cefoxitin (CEF), levofloxacin (LEV), and moxifloxacin (MXF) and reduced cell wall permeability, while the silence and knockout of grcC1 showed increased cell wall permeability and susceptibility to these drugs. Using CRISPR/Cpf1-assisted gene editing, we confirmed that the A132V mutation conferred low-level resistance to the aforementioned drugs in Mycobacterium abscessus and Mycobacterium smegmatis. Furthermore, thin-layer chromatography analysis indicated reduced glycolipid polarity in the grcC1 mutant strains, suggesting an impact on the cell envelope integrity. Our findings suggest that GrcC1 contributes to low-level drug resistance in mycobacteria by potentially reducing cell wall permeability, highlighting its potential as a novel target for antimicrobial agents and as a diagnostic marker.IMPORTANCEOur study uncovers a novel drug resistance mechanism in mycobacteria, focusing on the previously uncharacterized grcC1 gene. We identified a new mutation, A132V, in GrcC1, which is involved in cell wall component synthesis and menaquinone production. This mutation contributes to low-level resistance not only to linezolid but also to a broad range of drugs, including clarithromycin, vancomycin, and rifampicin. Through advanced techniques like CRISPR interference and gene editing, we demonstrated that GrcC1 plays a critical role in drug susceptibility and cell wall permeability across multiple Mycobacterium species. These findings represent the first connection between GrcC1 and drug resistance, offering new insights into combating infections caused by nontuberculous mycobacteria (NTM). Our work highlights the potential of GrcC1 as a target for novel therapeutic approaches and as a diagnostic marker for drug-resistant NTM infections.

Aquatic photochemistry for different dissociation forms of cephalosporin antibiotics: Degradation kinetics, products and photo-modified toxicity.

pH/H2O2 dual-responsive macrophage-targeted chitosaccharides nanoparticles to combat intracellular bacterial infection.

BackgroundSurgical site infections (SSI) make up ∼20% of all healthcare-associated infections (HAI), with 75% of SSI-associated deaths directly attributable to the SSI. Beta-lactams (BL) including cefazolin (CFZ) and cefoxitin (CFO) are recommended as surgical antibiotic prophylaxis (SAP). Cephalosporins are often avoided in patients with reported BL allergies despite cross-reactivity with penicillin at < 1%. Guidelines recommend giving SAP 60 min prior to incision. Cefazolin and cefoxitin pharmacokinetics (PK) exhibit rapid time to peak serum level and short elimination half-life. We aim to evaluate differences in SSI rate in patients who received CFZ or CFO vs. non-BL alternatives (BLA) and administration of preop BL dose at different time interval prior to incision.MethodsRetrospective observational study included patients aged 0 – 17 years who received SAP at CHOC from Jul 2021 – Jun 2023. Outcomes include differences in SSI rate within 90 days of surgery between patients receiving recommended BL (CFZ, CFO) vs BLA (clindamycin, gentamicin, metronidazole, vancomycin). Rate of SSI in patients who received pre-op CFZ or CFO at different time interval (0-20 min, 21-40 min, 41-60 min) will be examined. Wound classification (I to IV) as defined by CDC. SSIs were defined according to National Healthcare Safety Network. Bivariate logistic regression analyses compare the odds of experiencing an SSI between study groups.ResultsMedian age was 9.0 years [IQR: 3.0, 14.0], 58.8% males. Wound classification is as follows: 37.6% (Class I), 34.1% (Class II), 22.9% (Class III), and 5.1% (Class IV). Overall SSI occurred in 1.0% (92/9054) of procedures. Beta-lactams were used as SAP in 96% of procedures, with 89.8% receiving pre-op dose within 20 min of incision. Laparoscopic appendectomy was the most common procedure at 10.9%. Age < 1 year, use of non-BL SAP and administration of SAP >20 min from incision was associated with significant increase in SSI (p< 0.05, Table 1). No difference in SSI rate observed in patients who continued receiving post-op SAP for class I-II procedures.ConclusionOur study supports the continued use of CFZ, CFO compared to BLA for SAP. Pre-op doses of CFZ or CFO within 20 min of incision time were associated with decreased risk of SSI, likely due to their PK characteristics.DisclosuresAll Authors: No reported disclosures

Infections caused by Staphylococcus aureus are frequent in both public and medical settings. The objective of the current study was to assess the prevalence of the SEA and SEB genes in S. aureus clinical isolates. A hundred-sixty samples were obtained from several sources including wounds, urine samples, burns and respiratory tract, during period between October 2022 - January 2023, from Kadhimiya Hospital, Karkh General Hospital and Yarmouk Hospital. The samples were then subjected to several examinations including microscopic examination (gram staining), cultural characteristics on mannitol salt agar, hemolysis characteristic on blood agar and biochemical tests (oxidase, catalase, and coagulase), to confirm S. aureus isolates. These isolates were also subjected to several antibiotics to select the multi-drug resistant (MDR) isolates. Based on the results, high percentages of S. aureus isolates were found to be sensitive to antibiotics, All the isolates (100%) were sensitive to vancomycin (VA), 95.5% were sensitive to both chloramphenicol (C) and rifampin (RA), 93.2% were sensitive to clindamycin (DA), trimethoprim (TR), levofloxacin (LE), followed by 90.9, 88.6 and 75% were sensitive to oxacillin (OX), gentamicin (CN) and doxycycline (DO) respectively. However, 47.75 and 38.6% of isolates were resistant to azithromycin (AZM) and cefoxitin (CX) respectively. The frequency of SEA and SEB genes was estimated by polymerase chain reaction (PCR). The results revealed that, out of 27 S. aureus isolates tested, 8 had a single band for the SEA gene (102 bp), while 9 had a band for the SEB gene (164 bp). The findings indicated that the majority of S. aureus harboured both Sea and Seb genes.

A validated LC-MS/MS method for simultaneous quantitation of piperacillin, cefazolin, and cefoxitin in rat plasma and twelve tissues

Preoperative antibiotic options for pancreaticoduodenectomy (PD) include cefoxitin (CX), piperacillin-tazobactam (PT), or combined cefazolin and metronidazole (CM). Recent studies suggest the superiority of PT over CX, but evidence for CM is unclear. To explore the impact of preoperative antibiotic selection (CM vs. PT and CX vs. PT) on the development of surgical site infections (SSI). Consecutive adult patients at oneinstitution who underwent PDfrom November 2017 to December 2021 and received either CM, PT, or CX preoperatively, were included. The primary outcome was SSI. Secondary outcomes included postoperative infections and clinically significant postoperative pancreatic fistula (POPF). Logistic regression models were used. Among 127 patients included in the study, PT, CM, and CX were administered in 46 (36.2%), 44 (34.6%), and 37 (29.4%) patients, respectively. There were 32 (27.1%) SSI, 20 (36.1%) infections, and 21 (22.9%) POPF events. PT use was associated with reduced risk of SSI compared to CX (OR: 0.32, 95% CI: 0.11-0.89, p = 0.03), but there was no difference as compared to CM (OR: 0.75, 95% CI: 0.27-2.13, p = 0.59). There were no differences in secondary outcomes. PT reduced SSI rates compared to CX but was no different to CM among patients undergoing PDat our center.

Characterization of polymerized impurities in cefoxitin sodium for injection by two-dimensional chromatography coupled with time-of-flight mass spectrometry

Role of antibiotics in Milligan-Morgan hemorrhoidectomy for Grade III to IV Hemorrhoids: A randomized clinical trial

Methicillin-resistant Staphylococcus aureus (MRSA) can cause infection with higher morbidity and mortality. In the limited-resource setting, the availability of rapid detection is scarce and may not be available; therefore, prompt detection using the alternative method is indispensable. To compare the detection rate of the modified-conventional method with chromogenic media against mucocutaneous clinical swab, a total of 80 S. aureus isolates from previous studies were cultivated and re-cultured into routine media such as blood agar (BA) and mannitol-salt agar (MSA) between June and September 2018. It directly inoculated from plain blood agar that had been incubated previous day before; it further underwent inoculation to other media, such as chromogenic media (CHROMagar), blood agar and mannitol salt agar that had been supplemented with cefoxitin (CFOX) powder manually. The sensitivity MSA-CFOX and BA-CFOX, respectively, was 96.88%. On the other hand, the sensitivity of CHROMagar and MHA-CFOX was 90.62%. The specificity of each MHA-CFOX, MSA-CFOX, and CHROMagar is 87.5% as well as 93.75% for BA-CFOX. The study has demonstrated better performance of modified-conventional method compared to the other media. Hence, the application of modified-media should not be delayed to facilitate the findings of MRSA among hospitalized patients.

BackgroundAge and herb-drug combination are risk factors for the severity of Xiyanping injection (XYP) associated adverse events (AEs).ObjectiveTo analyze risk factors contributing to the severity of XYP’s AEs using a variable importance for projection (VIP) method.MethodsAEs related to the use of XYP were extracted from the China National Adverse Drug Reaction Monitoring Information System (2004–2017) and classified as general or severe. Data were analyzed with respect to age and 12 herb-drug combinations, including ribavirin (RB), ceftriaxone, penicillin sodium, ambroxol hydrochloride (AH), clindamycin, cefoxitin sodium, azithromycin (AZM), ceftazidime, amoxicillin sodium/potassium clavulanate, levofloxacin hydrochloride, sodium cefazolin pentahydrate, and acyclovir according to VIP scores and correlation coefficient (Coeff).ResultsA total of 21,714 AEs (general 20,660; severe 1054) related to XYP combinations were included. Using XYP alone tended to produce general AEs (All VIP = 3.124; 1.329; 1.857; 2.169; 2.400, Coeff < 0). For all set, 0–6 years old patients tend to have general AEs (VIP = 2.425, Coeff < 0), while those > 41 years old patients tend to have severe AEs (VIP = 1.180; 2.323, Coeff > 0). For 0–40 years old patients, XYP-RB combination had a greater impact on the severity of AEs (VIP = 1.158; 1.360; 1.147, Coeff > 0). For 7–17 years old patients, XYP-AZM combination tended to produce general AEs (VIP = 1.502, Coeff < 0). In individuals > 65 years old, XYP-AH combination tended to result in severe AEs (VIP = 1.232, Coeff > 0).ConclusionsVIP method was expected to effectively analyze risk factors in affecting the severity of AEs and control AEs more effectively. Age is the key factor contributing to the severity of AEs, and there are different influence directions. It is recommended that clinicians pay closer attention to the metabolic characteristics of different age groups. It is safe to use XYP alone and strictly implementing standardized operations such as medication interval and flushing will avoid undesired AEs.

The antibacterial activity of red propolis extract (RPE) and brown propolis extracts (BPE) and the synergistic effect of RPE with cefoxitin (CEFO), imipenem (IMI), and ertapenem (ERTA) was evaluated in vitro against methicillin-resistant Staphylococcus aureus (MRSA) strains. MRSA ATCC 33591, community-associated (CA-MRSA) USA300, and four clinical isolates were used. A broth microdilution assay was performed to obtain inhibitory and bactericidal concentrations of BPE, RPE, CEFO, IMI, and ERTA. RPE in combination with CEFO, IMI, and ERTA was evaluated on the formation or eradication of biofilm. The bacterial relative membrane conductivity of the strains was assessed after RPE and combinations exposition. Surface/binding computational analyzes between RPE compounds and penicillin binding protein 2a (PBP2a) were performed. BPE samples had no activity against MRSA (MICs 3.2-5 g l-1; MBCs 10-15 g l-1), so the subsequent assays were carried out only with RPE and antimicrobials. RPE exerted a bacteriostatic action (MICs 0.0156-0.125 g l-1; MBCs 0.5-2 g l-1) but the combinations with IMI and ERTA showed the highest inhibition, as observed in the time-kill curve. However, the FICI index showed synergism (≥0.5) only to RPE+IMI. This combination was the most effective in inhibiting the biofilm and showed the highest values of membrane conductivity. Computational predictions indicated that RPE constituents may interact with PBP2a. RPE and RPE+IMI exerted an antibacterial and antibiofilm activity on MRSA strains probably due to membrane/wall damage and interactions with PBP2a.

Antibiotic application during the perinatal period is unavoidable in the clinic, but the potential effects on mothers and infants remain unknown. Herein, 25 breast milk samples from mothers who received cefuroxime (CXM) or CXM + cefoxitin (CFX) treatments and fecal samples from their infants were collected to investigate the undesirable effects of antibiotics on the microbiota of mothers and neonates. Furthermore, five fecal samples of infants, whose mothers had antibiotic treatments, were collected at a 6-month postpartum follow-up visit to evaluate the long-term effects on infants’ gut microbiota. Moreover, the relative abundance of antibiotic resistance genes (ARGs) in fecal samples was compared to investigate the transfer of ARGs in the infant gut microbiota. The results indicated that the antibiotic treatments had no influence on the microbiota of breast milk. The dominant bacterial phyla in the fecal samples changed to Firmicutes and Proteobacteria after antibiotic treatments, while the bacterial community showed a recuperative trend at the follow-up visits. In addition, the abundance of ARGs in the infant gut microbiota demonstrated a declining trend in the CXM- and CXM + CFX-treated groups, while ARG abundance presented a significant increasing trend after a 6-month recovery period.Conclusion: Antibiotic treatments for mothers during the perinatal period disturb the gut microbiota in neonates. The infants’ gut microbiota would partly return to their initial state after rehabilitation, but the transfer of ARGs would leave the hidden trouble of antibiotic resistance. Overall, the data presented here can help to guide the scientific use of antibiotics during the perinatal period and provide potential approaches to mitigate the negative consequences.What is Known:• Antibiotic application during the perinatal period is unavoidable in the clinic.• Misuse of antibiotics can cause various unintended consequences, especially for antibiotic resistance.What is New:• Antibiotic treatments had no influence on the microbiota of breast milk but greatly disturbed the gut microbiota composition in infants.• The gut microbiota in infants would partly return to its initial state after rehabilitation but the transfer of ARGs would leave the hidden trouble of antibiotic resistance.

The essential oils were obtained by hydrodistillation from aerial parts of Mentha pulegium L. (M. pulegium L.) and Artemisia herba alba (A. herba alba) Asso. and analyzed by gas chromatography–flame ionization detector chromatograpy (GC–FID) and gaz chromatography–mass spectrometry (GC–MS). The antibacterial activities of the oils were determined by the disk diffusion method and a microdilution broth assay against six bacteria stains. The combinations of these essential oils with antibiotics were evaluated against two multi-drug-resistant bacteria strains: imipenem-resistant Acinetobacter baumannii (IRAB S3310) and methicillin-resistant Staphylococcus aureus (MRSA S19). The chemical analysis of M. pulegium essential oil revealed the presence of pulegone (74.8%) and neoisomenthol (10.0%). A. herba alba essential oil was characterized by camphor (32.0%), α-thujone (13.7%), 1,8-cineole (9.8%), β-thujone (5.0%), bornéol (3.8%), camphene (3.6%), and p-cymene (2.1%). All strains tested except Pseudomonas aeruginosa were susceptible to these oils. The combinations of essential oils with antibiotics exerted synergism, antagonism, or indifferent effects. The best effect was observed with A. herba alba essential oil in association with cefoxitin (CX) against MRSA S19. However, for IRAB S3310, the strongest synergistic effect was observed with M. pulegium in association with amikacin (AK). This study demonstrated that M. pulegium and A. herba alba essential oils have antibacterial activities which could be potentiated by antibiotics especially in the case of IRAB S3310.

Recognition and binding of FEZ-1 from Legionella with penicillin V and cefoxitin by fluorescence spectra in combination with molecular dynamics simulation

ABSTRACT: Staphylococcus epidermidis (S. epidermidis) is the Gram-positive strain which is one of the major causes of laboratory acquired infections. Infections caused by staphylococcus strains are becoming more demanding to treat because many of the strains are resistant to the antibiotics and chemotherapeutic agents. The aim of this study was to determine the antibiotic susceptibility of isolates of S. epidermidis which had been isolated from the microbiology laboratory of Lahore Garrison University, Lahore. Antibiotic Sensitivity against many antibiotics such as TPZ (tazobactum), ME (methicillin), CX (cefoxitin), P (penicillin), CTX (Cefotaxime), CEP (Cefepime) was determined for the identification of the most effective antibiotics against the infectious strains of S. epidermidis and zone of inhibition was measured. The results showed that out of 10 isolates, all the isolates were resistant against ME, while 9 of them were susceptible against TPZ. A remarkable difference was observed in the susceptibility pattern of S. epidermidis against TPZ rather than that of ME. Therefore, TPZ was the most effective antibiotic against the S. epidermidis infections which can be used to treat the infections. According to the present situation, the rampant use of antibiotics shouldbe prevented; otherwise it would become an uncontrollable problem to tackle these super bugs in near future.

Objective To monitor the drug resistance status of yersinia isolates from fresh meat, grasp the drug resistance spectrum and trend of Yersinia isolates in Our province, and provide important reference data for guiding the rational application of antibiotics in human clinical practice and controlling the spread of drug resistant strains. Methods A total of 600 pieces of fresh pork, beef and chicken were collected from several farmers' markets and supermarkets in Changchun every month for 15 months from August 18th to October 19th. 80 strains of Yersinia strains were detected, and MIC concentrations of drug resistance were detected by microbroth dilution with 15 antibiotic sensitive plates. Results 80 strains of Yersinia strains were counted. The total drug resistance rate of Yersinia pestis was 98.8%, and cefazolin (CFZ) had the highest drug resistance rate of 92.5.% (74/80). Erythromycin (ERY) was followed by 58.8% (47/80). Ampicillin (AMP) 57.5% (46/80); Naproxil acid (NAL) and cefoxitin (CFX) were 28.8 (23/80) and were somewhat resistant to other antibiotics. But all strains were sensitive to imipenem (IMP) and gentamicin (GEN). There were 28 strains with multiple drug resistance, accounting for 35.4% (28/79). Conclusion There are multiple antibiotic resistance in Yersinia strains in this monitoring, and the multiple drug resistance is serious and the resistance spectrum is diverse. In order to ensure food safety and human health, great attention should be paid to and enhanced drug resistance monitoring of Yersinia.

Purpose:To investigate the hand microbiome of Health Personnel and the flora transferred to their hands from cell phones. Methods:The study was conducted in a tertiary care hospital over 3 months in 50 health personnel. Their dominant hand was placed on agar plates to establish the hand microbiome. After sanitizing and drying their hands, and using their phones for a few minutes, another handprint was taken to identify the bacteria on the phone. The bacteria were identified by standard microbiologic techniques. Results:Organisms identified in the normal microbiome included coagulase negative Staphylococci (CoNS, 90%), Klebsiella pneumoniae (16%), E. coli (8%), Staphylococcus aureus (4%), Pseudomonas aeruginosa (2%) and Acinetobacter spp. (2%). CoNS isolated were found to be resistant to co-amoxiclav (41.67%), cotrimoxazole (20.83%), erythromycin (20.83%) and clindamycin (20.83%). Maximum resistance was observed towards co-amoxiclav. The repeat handprint showed the colony count as decreased by four times. Bacteria found were CoNS (92%), E. coli (4%), Enterococcus (4%), Klebsiella (2%) and Acinetobacter (2%). Antibiotic sensitivity was similar here with additional resistance to cefepime and cefoxitin by CoNS. Conclusion:Hand microbiome of health personnel comprises bacteria that are dangerous to immunocompromised individuals and our phones are effectively transmitting multidrug resistant bacteria to our hands within a few moments of contact. There was also a notable lack of S. aureus in our samples, while many other studies have shown it to be a common nosocomial pathogen, found on hands of health personnel. Keywords:Hand microbiome, Health Personnel, Antibiotic resistance, cell phone