Combination Of Clarithromycin Research Articles

QUANTIFICATION AND QUALITY CONTROL OF TRIPLE-DRUG COMBINATION EMPLOYED FOR GASTRIC ULCER USING STABILITY-INDICATING SELECTIVE RP-HPLC TECHNIQUE

Objective: A seven-day regimen consisting of vonoprazan (VNP), amoxicillin (AXC) and clarithromycin (CRC), administered twice daily, has been permitted and reimbursed by health coverage as initial therapy. No technique has been implemented yet to determine the quantities of VNP, AXC, and CRC combination. This work effectively aimed at estimating these medications (VNP, AXC, and CRC) at the same time by developing an HPLC technique that saves money and time. Methods: The VNP, AXC, and CRC were separated in a “Waters” column (C18 nature; 250 mm sized length; 4.6 mm sized internal diameter; 5 µm sized particle; 25 °C temperature). Phosphoric acid (0.1% in water; pH 4.2) and absolute methanol (50:50, v/v) comprise the mobile phase. The drug product, Voqueznatripak, was subjected to hydrolysis, oxidation, photolysis, and thermal stressors with the intent to cause enforced degradation. The suggested "HPLC conditions" were verified in compliance with ICH guidance. Results: The measurements had a linear range of 10–20 µg/ml for VNP and 250–750 µg/ml for AXC and CRC. The AXC, CRC, and VNP had LOQ’s 5.302 µg/ml, 5.487 µg/ml and 0.523 µg/ml, respectively. Precision measurements were<0.2% RSD and accuracy ranges were 99.40% to 101.46%. The newly devised “HPLC conditions” specificity attribute and stability-indicating quality were also validated by forced degradation tests. Conclusion: The newly devised “HPLC conditions” for analysing AXC, CRC, and VNP in formulation dosage form and stability samples might be adapted by quality control laboratories. The devised “HPLC conditions” is qualified and consistent to reveal and detect any probable change in the drug product assessments throughout stability experiments.

A Review of the Association between Infections, Seizures, and Drugs.

Seizures are a common presenting symptom of the central nervous system (CNS) and could occur from infections (such as toxins) or drugs. The aim of this study was to present a systematic review of the association between infections, seizures, and drugs. Through February 18, 2024, according to the PRISMA guidelines and based on the PICO standard format, relevant, in-depth consequent guide approach and evidence-based options were selected associated with a knowledgeable collection of current, high-quality manuscripts. Imbalance between inhibitory and excitatory neurotransmitters due to infections, drugs such as ticarcillin, amoxicillin, oxacillin, penicillin G, ampicillin, tramadol, venlafaxine, cyclosporine, tacrolimus, acyclovir, cellcept, the old generation of antiepileptic drugs, such as carbamazepine, phenytoin, and many other drugs could cause different stages of CNS disturbances ranging from seizure to encephalopathy. Infections could cause life-threatening status epilepticus by continuous unremitting seizures lasting longer than 5 minutes or recurrent seizures. Meningitis, tuberculosis, herpes simplex, cerebral toxoplasmosis, and many others could lead to status epilepticus. In fact, confusion, encephalopathy, and myoclonus were reported with drugs, such as ticarcillin, amoxicillin, oxacillin, penicillin G, ampicillin, and others. Penicillin G was reported as having the greatest epileptogenic potential. A high dose, in addition to prolonged use of metronidazole, was reported with seizure infection. Meropenem could decrease the concentration of valproic acid. Due to the inhibition of cytochrome P450 3A4, the combination of clarithromycin and erythromycin with carbamazepine needs vigilant monitoring. Due to changes in drug metabolism, co-administration of antiseizure drugs and antibiotics may lead to an enhanced risk of seizures. In patients with neurocysticercosis, cerebral malaria, viral encephalitis, bacterial meningitis, tuberculosis, and human immunodeficiency virus, the evidence-based study recommended different mechanisms mediating epileptogenic properties of toxins and drugs.

Pharmacokinetic Interactions Between Tegoprazan and the Combination of Clarithromycin, Amoxicillin and Bismuth in Healthy Chinese Subjects: An Open-Label, Single-Center, Multiple-Dosage, Self-Controlled, Phase I Trial.

Tegoprazan is a potassium-competitive acid blocker that inhibits gastric acid and which may be used for eradicating Helicobacter pylori. This study focuses on the pharmacokinetic interaction and safety between tegoprazan and the combination ofclarithromycin, amoxicillin and bismuth in healthy Chinese subjects. An open-label, three-period, single-center, multiple-dosage, single-sequence, phase I trial was conducted in 22 healthy subjects. In period 1, the subjects took tegoprazan 50 mg twice daily for 7 days, and in period 2 they were administered clarithromycin 500 mg, amoxicillin 1000 mg and bismuth potassium citrate 600 mg twice daily for 7 days (days 14-20). Tegoprazan, clarithromycin, amoxicillin and bismuth potassium citrate were then administered in combination for 7 days (days 21-27) in period 3. Blood samples were collected up to 12h after the last dose of each period. Safety assessments were performed in each period. The geometric mean ratios (GMRs) [90% confidence interval (CI)] of maximum plasma concentration at steady state (Cmax,ss) and area under the plasma concentration-time curve over the dosing interval (AUCτ) at steady state were 195.93% (175.52-218.71%) and 287.54% (263.28-314.04%) for tegoprazan and 423.23% (382.57-468.22%) and 385.61% (354.62-419.30%) for tegoprazan metabolite M1, respectively. The GMRs (90% CI) of Cmax,ss and AUCτ were 83.69% (77.44-90.45%) and 110.30% (102.74-118.41%) for clarithromycin, 126.25% (114.73-138.93%) and 146.94% (135.33-159.55%) for 14-hydroxyclarithromycin, 75.89% (69.73-82.60%) and 94.34% (87.94-101.20%) for amoxicillin, and 158.43% (125.43-200.11%) and 183.63% (156.42-215.58%) for bismuth, respectively. All reported adverse events were mild. The frequency of adverse events during the coadministration stage was not higher than that during the single- or triple-drug administration stages. The plasma exposure of tegoprazan, M1, 14-hydroxyclarithromycin and bismuth was increased after the coadministration of tegoprazan, clarithromycin, amoxicillin and bismuth. The coadministration exhibited favorable safety and tolerability. CTR20230643.

Combined Application of Juniperus communis Essential Oil and Amikacin, Clarithromycin and Rifampicin against Mycobacterium avium and Mycobacterium intracellulare

The group of nontuberculous mycobacteria (NTM) includes about 200 mycobacteria that are widespread in the natural environment as free-living saprophytic bacteria, commensals or symbionts. NTM, also referred to as atypical mycobacteria, are mostly apathogenic; nowadays, they are increasingly important environmental opportunistic pathogens. This study continues the work of previous studies which investigated the individual and synergistic effect of different essential oils (EOs) on NTM. The aim was to investigate the effect of the interaction of the common juniper (Juniperus communis) EO and the antimicrobials, amikacin, clarithromycin and rifampicin, against Mycobacterium avium and M. intracellulare using the checkerboard synergy method in an enriched Middlebrook 7H9 broth. Morphological changes of treated NTM cells were observed with a transmission electron microscope. The most synergistic combinations were found at subinhibitory concentrations of the common juniper EO and rifampicin against both tested NTM and this EO and clarithromycin against M. avium. A slightly smaller number of synergistic effects on both NTM were found using a combination of this EO and amikacin. Combinations of clarithromycin and the common juniper EO showed no synergism against M. intracellulare. The exposure of both NTM to synergistic combinations of this EO and antimicrobials caused significant morphological changes in mycobacterial cells. Synergism with the combined use of EOs and antimicrobials allows the use of low effective concentrations via the sustained antimicrobial effect of the tested substances, but with potentially reduced toxicity.

Efficacy of adjunctive topical liposomal clarithromycin on systemic Glucantime in Old World cutaneous leishmaniasis: a pilot clinical study.

Aim: This study aimed to investigate the effects of topical liposomal clarithromycin in combination with meglumine antimoniate (Glucantime®) on cutaneous leishmaniasis (CL) lesions. Methods: This pilot, randomized, double-blinded clinical trial was conducted on patients with CL lesions. Patients were randomly assigned to two groups: the first group received liposomal clarithromycin in combination with Glucantime for 28days, while the second group received Glucantime and a placebo. Afterward, patients were followed up at 1.5, 3, and 6months after treatment initiation and were evaluated for recovery time, induration, and size of the lesions. Results: Sixty patients with CL lesions were divided into two separate groups with 30 members each and were examined. Within-group analysis revealed that recovery time in the clarithromycin group was 26.65 ± 5.12days, while in the placebo group, it was 32.84 ± 24.43, which was statistically insignificant (p = 0.18). Lesion size comparison in the first and last follow-ups reduced in both groups: 7.73 ± 4.31 to 0.48 ± 0.50 in the clarithromycin group (p = 0.006) and 5.47 ± 5.83 to 0.76 ± 0.88 in the placebo group (p = 0.03). Moreover, the size of lesions in the intervention group was significantly reduced compared to that in the placebo group (p = 0.02). Recognizable induration reduction was observed in the clarithromycin group (2.60 ± 0.77 to 1.0 ± 0.00). No adverse effects attributable to clarithromycin were reported. Conclusion: The administration of liposomal clarithromycin in combination with systemic Glucantime had a significant beneficial effect on reducing lesion size in leishmaniasis. Further studies on larger populations are recommended. Systematic Review Registration: https://www.irct.ir/trial/46611.

Poly(lactic acid)/clarithromycin with metals dioxides nanoparticles: Preparation and performance under ultraviolet irradiation

Different polylactic acid (PLA) thin films containing clarithromycin and a number of metal oxide nanoparticles (magnesium, titanium, zinc, and nickel) dioxides were created. Low dosages of metal oxides (0.01% by weight) and clarithromycin (0.5% by weight) were used to make transparent films. The role of metal oxide nanoparticles and clarithromycin as UV blockers for PLA photodegradation was looked at. The durability of polymeric materials is improved more by clarithromycin in combination with metal oxides than by clarithromycin alone in PLA films. An analysis of the weight loss, surface morphology, and changes in infrared spectra of irradiated polymeric blends revealed that nickel oxide and clarithromycin together function as effective UV blockers and offer PLA a high degree of protection. Nickel oxide nanoparticles were the best addition for PLA stability. Highly alkaline metal oxides are present. Contrarily, the heteroatom and aromatic nature of clarithromycin enables it to absorb damaging radiation and function as an ultraviolet absorption. Thus, the adaptability of PLA to photodegradation was significantly improved by using a mixture of metal oxide nanoparticles and clarithromycin.

Current Trends in the Management of Port-Site Infections: A Case Series and a Review of Published Work.

Introduction Laparoscopic techniques have become standard for many surgeries, offering benefits such as quicker recovery and less pain. However, port-site infections (PSIs) can occur and pose challenges. PSIs can be early (within seven days) or delayed (after three to four weeks), with delayed PSIs often caused by non-tuberculous mycobacteria (NTMs). NTMs are difficult to treat and do not respond well to antibiotics, leading to prolonged and recurrent infections. Guidelines for PSI management are limited. This summary highlights a case series of 10 patients with PSIs, discussing their treatment experience and presenting a treatment algorithm used at our institute. Methods This is a retrospective study (2015-2020) on chronic port-site infections (PSIs) in laparoscopic surgeries. Data were collected on patient demographics, surgery type, prior treatment, and management at the institute. Results The study analyzed 10 patients with chronic PSIs following laparoscopic surgery between 2015 and 2020. Laparoscopic cholecystectomy was the most frequent index surgery. Three patients had a history of treatment with varying durations of anti-tubercular therapy, one of whom had completed anti-tubercular treatment prior to presentation. Complete surgical excision with histopathological examination and fungal, bacterial and mycobacterial cultures were performed. Seven of the 10 patients were treated with oral ciprofloxacin and clarithromycin combination therapy for three months, two were treated with culture-based antibiotics and one was treated with anti-tubercular therapy. All patients improved on treatment.Themean follow-up period was52 ± 9.65 months, with no relapses being reported. Conclusion Port-site infections (PSIs) are troublesome complications of laparoscopic surgery that can erode the benefits of the procedure. Delayed PSIs caused by drug-resistant mycobacteria are difficult to treat. Improved sterilization methods and thorough microbiological work-up are crucial. Radical excision and prolonged oral antibiotics are effective treatments. Clinicians should avoid empirical antibiotic therapy to prevent antimicrobial resistance.

Comparative Effectiveness of Ceftriaxone Alone and in Combination with Clarithromycin for Paediatric Patients Hospitalized with Community Acquired Pneumonia

Background: Guidelines for treatment of community acquired pneumonia suggests empirical therapy with combination of clarithromycin and ceftriaxone when infection with mycoplasma pneumoniae is considered. But there is limited evidence available. Aim: To ascertain effectiveness of ceftriaxone alone verses the combination of ceftriaxone and clarithromycin with respect to cure and length-of-stay and total hospital cost. Methodology: A randomized control trial with 128 patients of age 2 months to 5 years was conducted at Department of Paediatrics, Shaikh Zayed Hospital Lahore from 1st October 2017 to 30th September 2018. Patients selected according to selection criteria through non probability sampling technique and randomly divided into two groups. Antibiotics given according to study objectives, comparative analysis done, and chi square test applied. Results: The mean age of patients were 27.02±19.28 months in group A and 29.06±18.29 months in group B. In both groups most of the patients were under the age of 40 months. 72% cured in group A while 86% cured in group B. 80% patients stayed in hospital for 3 days in Group A while, 59% patients in group B. 69% patients had cost effectivity in group A while 84% in group B. Conclusion: The combination of Ceftriaxone and Clarithromycin was more advisable in treating pnemounia verses the use of ceftriaxone alone. Keywords: Community acquired pneumonia, Ceftriaxone alone, Ceftriaxone and clarithromycin, Mycoplasma pneumonia

The synergetic effect of sitafloxacin–arbekacin combination in the Mycobacterium abscessus species

Mycobacterium abscessus species (MABS) is the most commonly isolated rapidly growing mycobacteria (RGM) and is one of the most antibiotic-resistant RGM with rapid progression, therefore, treatment of MABS is still challenging. We here presented a new combination treatment with sitafloxacin that targeted rough morphotypes of MABS, causing aggressive infections. Thirty-four clinical strains of MABS were isolated from various clinical samples at the Juntendo university hospital from 2011 to 2020. The susceptibility to a combination of sitafloxacin and antimicrobial agents was compared to that of the antimicrobial agents alone. Out of 34 MABS, 8 strains treated with sitafloxacin–amikacin combination, 9 of sitafloxacin–imipenem combination, 19 of sitafloxacin–arbekacin combination, and 9 of sitafloxacin–clarithromycin combination showed synergistic effects, respectively. Sitafloxacin–arbekacin combination also exhibited the synergistic effects against 10 of 22 Mycobacterium abscessus subspecies massiliense (Mma) strains and 8 of 11 Mycobacterium abscessus subspecies abscessus (Mab) strains, a highly resistant subspecies of MABS. The sitafloxacin–arbekacin combination revealed more synergistic effects in rough morphotypes of MABS (p = 0.008). We demonstrated the synergistic effect of the sitafloxacin–arbekacin combination against MABS. Further, this combination regimen might be more effective against Mab or rough morphotypes of MABS.

1697. Dose-response Studies of the Novel Bacterial Leucyl-tRNA Synthetase Inhibitor, Epetraborole, in the Intracellular Hollow Fiber System Model of Mycobacterium avium complex Lung Disease

Abstract Background Based on meta-analyses the current standard-of-care regimen (SOC) for Mycobacterium avium complex (MAC) lung disease achieves a sustained sputum conversion rate of ∼54% at best. Epetraborole (EBO) is a boron-containing oral inhibitor of bacterial leucyl-tRNA synthetase, an essential enzyme in protein synthesis; EBO demonstrates potent activity against nontuberculous mycobacteria. To identify EBO exposure-effect parameters we used the intracellular hollow fiber system model of intracellular pulmonary MAC (HFS-MAC). Methods EBO was administered once daily at 8 different doses to HFS-MAC replicates for 28 days to achieve a half-life (t½) of 10.4h and the 0-24h area under the concentration-time curves (AUC0-24) that cover the observed AUC values in humans. The SOC combination of clarithromycin (CLR), ethambutol (EMB), and rifabutin (RFB) at human intrapulmonary pharmacokinetic (PK) concentrations was used. The central compartment of each HFS-MAC unit was sampled throughout the 28 days to assess PK parameters as was the peripheral compartment for total bacterial burden and the EBO-resistant bacterial burden. EBO AUC versus total MAC burden was modeled using the inhibitory sigmoid maximal effect (Emax) model. EBO AUC versus EBO-resistant MAC burden was modeled using a quadratic function. Results Measured EBO concentrations demonstrated a t1/2 of 10h. For SOC, the AUC for CLR, EMB, and RFB was 60 mg*h/L (t1/2=6h), 39 mg*h/L (t1/2=8h), and 1.5 mg*h/L (t1/2=45h), respectively, similar to human lung concentrations. Changes in MAC burden over 28 days (Fig. 1) show that highest EBO exposures matched SOC until day 14. The exposure versus effect on each sampling day is shown in Fig. 2. The EBO AUC mediating 50% of Emax (EC50) was an AUC of 22 mg*h/L (95% confidence interval [CI]: 16-70), and the EC80 was an AUC of 47.5 mg*h/L (CI: 34.6-151.2). The relationship between AUC and EBO-resistant subpopulation (Fig. 3) shows that an AUC0-24 of 47.5 mg*h/L, the same as the EC80 for microbial kill, was associated with resistance suppression, as was the addition of SOC to EBO. Figure 1.Changes in bacterial burden over the 28-day dosing period. Bacterial burden on serial samples from all HFS-MAC units and replicates over 28days are shown. The highest epetraborole exposures demonstrated the same effectiveness as the three drug SOC until day 14, after which it failed as resistance emerged. On the other hand adding epetraborole at an AUC of 43.6 mg*h/L to the SOC led to much faster kill (i.e, higher kill slopes) than SOC or the epetraborole monotherapy at the same AUC. Figure 2.Epetraborole exposure versus effect on bacterial burden. Shown are inhibitory sigmoid Emax curves for epetraborole AUC versus log10 CFU/mL on each sampling day, as well as various extents of microbial kill such as stasis (holding burden similar to day 0), 1 log CFU/mL kill and 2 log CFU/mL kill. Beyond day 3, epetraborole killed > 1log CFU/mL, which means it was rapidly bactericidal. Figure 3.Epetraborole exposure versus epetraborole-resistant subpopulation. Drug-resistant burden is shown as log10 CFU/mL. The addition of SOC to EBO totally suppressed emergence of any resistance on all days. Conclusion EBO monotherapy with an AUC0-24 > 16.9 mg*h/L killed > 1.0 log10 CFU/mL of MAC compared to day 0. At the EC80, EBO killed at least 2.0 log10 CFU/mL, thus was highly bactericidal. EBO plus SOC demonstrated resistance suppression. Disclosures Moti Chapagain, MD, PhD, Praedicare Inc.: Stocks/Bonds Shruti Athale, PhD, Praedicare Inc.: Stocks/Bonds Jotam Pasipanodya, MD, PhD, Praedicare Inc.: Employee MRK Alley, PhD, ABBOTT LABS: Stocks/Bonds|ABBVIE: Stocks/Bonds|AN2 Therapeutics: Author on epetraborole patent|AN2 Therapeutics: Salary|AN2 Therapeutics: Ownership Interest|AVANOS MED INC: Stocks/Bonds|NABRIVA THERAPEUTICS PLC: Stocks/Bonds|NOVARTIS AG: Stocks/Bonds Tawanda Gumbo, MD, Hydronium Biopharma: Ownership Interest|Hydronium Biopharma: Stocks/Bonds|Praedicare Africa Pvt Ltd: Board Member|Praedicare Africa Pvt Ltd: Ownership Interest|Praedicare Africa Pvt Ltd: Stocks/Bonds|Praedicare Inc.: Patents|Praedicare Inc.: Ownership Interest|Praedicare Inc.: Stocks/Bonds.

The Use of Combination of Clarithromycin -Nano Oxide Nanoparticles to Doping PVC to Protect it from Photodegradation

Films of polyvinyl chloride with oxide nanoparticles (MgO, NiO, TiO2, and ZnO) and clarithromycin were prepared. Oxide nanoparticles were used in low concentrations (0.01% by weight) along with clarithromycin. The analysis of oxide nanoparticles and clarithromycin as UV blockers for PVC photodegradation investigations into weight loss, surface morphology, and IR changes, revealed that titanium oxide, especially, protects PVC from harmful ultraviolet light.

Surgical management of parotid non-tuberculous mycobacteria lymphadenitis in children: A pediatric tertiary-care hospital's experience

ObjectiveNon-tuberculous mycobacteria (NTM) represents an important etiology of cervicofacial lymphadenitis (CFL) and skin/soft tissue infections in children. It can also affect the salivary glands, including the parotid gland, which is unique due to the presence of intra-salivary lymph nodes. There are no established guidelines for treatment of NTM CFL. NTM lymphadenitis was historically surgically treated; recently the literature supports initial medical treatment. Treatment decisions have been dependent on the extent of disease, preference of providers, and risk of surgical complications. The goal is to report our experience in surgical outcomes of NTM CFL with involvement of the parotid gland after pre-operative medical management. MethodsA retrospective case series of patients with NTM affecting the parotid gland at a tertiary care pediatric hospital between 2004 and 2020. ResultsSeventy-two patients were referred for surgical evaluation of possible parotid NTM. Thirty-three patients underwent surgical excision. Fifteen patients were identified with presumed NTM infection involving the parotid gland. There were twelve females and three males with a mean age of 2.0 years (SD 1.55; range 1–6 days) at the time of surgery. All underwent surgical excision with parotidectomy. The most common pre-operative antimycobacterial therapy used was a combination of clarithromycin and rifampin. All 15 patients had pathological findings consistent with NTM infection (granulomatous lymphadenitis). Forty percent (n = 6) of patients had positive stains with acid-fast bacilli (AFB), with Mycobacterium avium as the most common species (n = 5). The majority of patients, 86.67% (n = 13), had complete resolution of infection after surgery. Clarithromycin and rifampin were the most common post-operative antimycobacterial treatment (mean 81.5 days, SD 110.14, range 2–411 days). The most common complication experienced was acute (<3 months) lower facial nerve paresis (40%, n = 6), but no patient had permanent facial paralysis. Conclusion and RelevanceParotidectomy is a safe and efficacious treatment in patients with NTM CFL affecting the parotid gland after incomplete resolution with antimycobacterial therapy. Further investigation to optimize duration of antimycobacterial treatment is necessary. We highlight the experience of a high-volume tertiary care pediatric hospital with surgical management of this disease.

Comparative efficacy of azithromycin versus clarithromycin in combination with beta-lactams to treat community-acquired pneumonia in hospitalized patients: a systematic review.

ObjectiveThe objective was to compare the efficacy of azithromycin and clarithromycin in combination with beta-lactams to treat community-acquired pneumonia among hospitalized adults.MethodsFive databases (PubMed, Google Scholar, Trip, Medline, and Clinical Key) were searched to identify randomized clinical trials with patients exposed to azithromycin or clarithromycin in combination with a beta-lactam. All articles were critically reviewed for inclusion in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.ResultsSeven clinical trials were included. The treatment success rate for azithromycin–beta-lactam after 10 to 14 days was 87.55% and that for clarithromycin–beta-lactam after 5 to 7 days of therapy was 75.42%. Streptococcus pneumoniae was commonly found in macrolide groups, with 130 and 80 isolates in the clarithromycin-based and azithromycin-based groups, respectively. The length of hospital stay was an average of 8.45 days for patients receiving a beta-lactam–azithromycin combination and 7.25 days with a beta-lactam–clarithromycin combination.ConclusionMacrolide inter-class differences were noted, with a higher clinical success rate for azithromycin-based combinations. However, a shorter length of hospital stay was achieved with a clarithromycin–beta-lactam regimen. Thus, a macrolide combined with a beta-lactam should be chosen using susceptibility data from the treating facility.

Synergistic combinations of clarithromycin with doxycycline or minocycline reduce the emergence of antimicrobial resistance in Rhodococcus equi.

The alarming increase in rifampin and macrolide resistance among Rhodococcus equi isolates highlights the need to identify alternative therapeutic options that can effectively control rhodococcosis in foals while limiting the further development of drug resistance. To evaluate bacterial killing, antibiotic synergism and mutant prevention concentrations (MPCs) of clarithromycin alone and in combination with doxycycline, minocycline or rifampin against clinical isolates of R equi. In vitro experiments. Bacterial time-kill, fractional inhibitory concentration (checkerboard) and mutant prevention concentration assays were evaluated in four clarithromycin- and rifampin-susceptible (ClaS /RifS ) and two clarithromycin- and rifampin-resistant (ClaR /RifR ) R equi clinical strains. In this study evaluating a limited number of isolates, combinations of clarithromycin with doxycycline or minocycline, but not with rifampin, were generally synergistic in both ClaS /RifS and ClaR /RifR strains as determined by checkerboard testing. In time-kill assays, all antibiotics, both alone and in combination, reduced viable ClaS /RifS R equi by more than 3 log10 at 24hours compared with control cultures without antibiotics. Combinations of clarithromycin with doxycycline, minocycline or rifampin induced significantly lower MPC values compared with the individual antimicrobials alone for all ClaS /RifS R equi strains, resulting in a narrower mutant selection window (MSW). However, clarithromycin/rifampin combination did not markedly decrease MPCs of the individual antimicrobials in ClaR /RifR R equi isolates, and the observed decrease in MPCs for doxycycline or minocycline did not generally differ when combined with clarithromycin. The number of analysed R equi isolates was limited. In vitro outcomes require clinical confirmation. Dual therapy combinations consisting of clarithromycin with doxycycline or minocycline merit consideration as a treatment protocol against R equi in foals due to in vitro synergy. These combination therapies may also minimise the emergence of antimicrobial resistance in cases of rhodococcosis.

A Randomized Placebo-Controlled Phase II Study of Clarithromycin or Placebo Combined with VCD Induction Therapy Prior to High-Dose Melphalan with Stem Cell Support in Patients with Newly Diagnosed Multiple Myeloma

▪Background: Uncontrolled studies and a case-matched study indicate that clarithromycin might exert synergistic effects in combination with thalidomide or lenalidomide in the treatment of multiple myeloma. Recent cellular studies have shown that the combination of clarithromycin and bortezomib results in increased cytotoxicity compared to bortezomib alone in myeloma cell lines. A possible mechanism underlying this synergistic effect might be simultaneous inhibition of the ubiquitin-proteasome system by bortezomib and the autophagy-lysosome system by clarithromycin resulting in enhanced endoplasmic reticulum stress-mediated apoptosis in myeloma cells (Moriya et al. Int J Oncol 2013).The Danish Myeloma Study Group (DMSG) initiated the CLAIM trial (NCT02573935), a randomized placebo-controlled phase II study, to investigate the efficacy and safety of clarithromycin in combination with the bortezomib containing VCD regimen.Methods: Patients with newly diagnosed multiple myeloma were randomized (1:1) to receive p.o. clarithromycin 500 mg or a matching placebo tablet twice daily for 63 days in combination with VCD induction therapy. The randomization was stratified according to International Staging System stage. The VCD consisted of 21-day cycles of subcut bortezomib 1.3 mg/sqm days 1, 4, 8, 11, i.v. cyclophosphamide 500 mg/sqm on days 1 and 8, and p.o. dexamethasone 40 mg days 1, 2, 4, 5, 8, 9, 11, 12. After induction treatment the patients proceeded to cyclophosphamide priming (2000 mg/sqm), leukapheresis and high-dose melphalan (200 mg/sqm) with hematopoietic stem cell support (HDT). Patients from six Danish hematology departments participated in the trial. Primary endpoint was to compare rate of very good partial response or better response after three cycles of VCD combined with clarithromycin or placebo. Important secondary end-points were to compare very good partial response or better response two months after HDT, number of stem cells harvested, frequency of infections and safety. The responses were assessed according to the IMWG criteria and analyses were by intention to treat.Results: The study was prematurely stopped for safety reasons after the inclusion of 58 patients (36% of the planned study population). The enrolled patients were randomly assigned to clarithromycin (27) or placebo (31), and the clinical characteristics at baseline were balanced (Table I). VGPR or better response after the VCD induction therapy was obtained in 12 patients (44.4%, (95% CI, [25.5 - 64.7]) and in 16 patients (51.6%, [33.1 - 69.8], P = 0.59) in the clarithromycin group and the control group, respectively. There was no difference in the secondary endpoints between the treatment groups (Table I). A total of 26 serious adverse events were reported in 16 (59.3%) patients in the clarithromycin group and 16 serious adverse events in 10 (32.3%) patients in the control group. Seven patients (25.9%) in the clarithromycin group developed severe gastrointestinal complications (SAE ≥ grade 3) comprising pain, neutropenic enterocolitis, paralytic ileus or peptic ulcer. These complications occurred in only one patient in the control group (Table I). Septicaemia with Gram negative bacteria was observed in 5 patients in the clarithromycin group. By contrast, the only case of septicaemia detected in the control group was pneumococcal sepsis associated with pneumonia. In consequence of this imbalance in occurrence of severe gastrointestinal symptoms and septicaemia the study safety board decided to stop inclusion of new patients and to stop administration of the study drug on 16 September 2016.Conclusion: The study was prematurely stopped due to a number of serious adverse events. Although we only could analyse response data in 58 included patients the data do not suggest any effect of clarithromycin when added to the VCD regimen and our trial does not encourage further clinical studies on the combination of clarithromycin and bortezomib. Surprisingly, our study found an increased frequency of serious adverse events, in particular serious gastrointestinal complications and septicaemia, in the clarithromycin group. It emphasizes the need for controlled studies on the effect of clarithromycin, both in assessment of potential anti-myeloma effects as well as assessment of safety measures. [Display omitted] DisclosuresAbildgaard:Takeda: Research Funding.

When Should Statins Be Stopped?

Mycobacterium chelonae is a non-tuberculous mycobacterium that can cause skin infections in immunocompetent individuals. We report a case of skin infection by this agent in a woman with dyslipidaemia, that culminated in statin-induced rhabdomyolysis due to the combination of clarithromycin, ciprofloxacin and simvastatin.LEARNING POINTSSkin infection with Mycobacterium chelonae is an increasing global problem among immunocompetent individuals.Statin-induced rhabdomyolysis is an important and avoidable end-result of drug–drug interaction.Inhibition of cytochrome P450 isoenzyme 3A4 and of organic anion transporting polypeptide 1B1 are two important examples of statin interference with metabolism, and clarithromycin can inhibit both.

Current development of &lt;i&gt;Helicobacter pylori&lt;/i&gt; eradication protocols

H. pylori is one of the most common commensal microorganisms in the human body, colonizing up to 60% of the inhabitants of all continents. Some strains of H. pylori have acquired virulent properties and their presence can significantly complicate the course of atrophic gastritis of type B, gastric ulcer and duodenal ulcer, as well as malignant diseases of the stomach. In such situations, eradication therapy seems to be pathogenetically justified. International recommendations for standard first-line triple eradication therapy, including a proton pump inhibitor (PPI), amoxicillin and clarithromycin in a course of 7–10 days, were proposed in 1996. Until the beginning of the XXI century, it was actively and with high efficiency (up to 90%) used everywhere, but later reports began to appear about a catastrophic decrease in results (up to 60%). Then it turned out that the effectiveness of the three-component (triple) therapy directly correlates with the resistance to clarithromycin, which has increased significantly in recent decades, and so necessitated the creation of new H. pylori elimination schemes. The results of various schemes for H. pylori eradication were analyzed, including variants of modified triple therapy associated with the inclusion of new drugs or an increase in the duration of eradication. In particular, it was proposed to replace amoxicillin with metronidazole. However, further studies have shown that the combination of clarithromycin with amoxicillin seems to be preferable, which is due to the high level of H. pylori resistance to metronidazole in many countries. Attempts to use probiotics in parallel, in particular cultures of various Lactobacillus species, were analyzed, which increases the level of eradication during standard triple therapy from 61.5 to 81.6%, and also significantly reduces the severity of side effects. It has been shown that a promising way to increase the effectiveness of 7-day first-line therapy schemes with clarithromycin is the use of modern effective PPIs (for example, esomeprazole or rabeprazole). The scheme of modified sequential therapy with the replacement of clarithromycin with tetracycline or levofloxacin, which has shown high efficiency, is considered. A variant of standard triple therapy modified into quadrotherapy with the addition of metronidazole or tinidazole was analyzed. It has been shown that the sequential therapy scheme is ineffective for eradication of multidrug-resistant strains. Ideally, the treatment of bacterial infections should be based on endoscopic sampling of gastric mucosa biopsies, followed by microbiological determination of the sensitivity of the isolated isolates to antibacterial drugs in vitro.

Antibiotic use for pneumonia in children under-five at a pediatric hospital inJeddah city, Saudi Arabia.

Background: Pneumonia has been a severe cause of morbidity and mortality among children belowfive years. Almost 1.3 million deaths occur in children due to pneumonia. The common signs andsymptoms of pneumonia include fever, cough, and Shortness of Breath (SOB). Antibiotics arecommonly used to treat Pneumonia, but it should be used in appropriate doses and duration.Aim: We aimed to review the results of antibiotic usage for treating pneumonia in children at atertiary hospital in Jeddah, Saudi Arabia. Method: A retrospective cohort study was done in November 2019 that involved 41 participantsbetween (0-5) years of both gender diagnosed with Community-Acquired Pneumonia (CAP). Result: In this study, we use about 14 kinds of antibiotics. There was no significant between theantibiotic and age group (p=0.269). Also, the relationship between the antibiotics and the frequencyused of antibiotics was significant (P=0.002). On the other hand, there was an association betweenantibiotics with inpatient and antibiotic (p=0.001), and the combination of Clarithromycin withCefuroxime (17.7%) was the most commonly used in both in-patients and out-patients. Conclusion: Our study found the combination of clarithromycin and cefuroxime the most commonnone of our patients were diagnosed with severe pneumonia. Using antibiotics to treat bacterialpneumonia in children should always be considered to prevent severe complications even though if the pneumonia is not severed.

The synergetic effect of Imipenem-clarithromycin combination in the Mycobacteroides abscessus complex

BackgroundNontuberculous mycobacteria (NTM) are ubiquitous organisms and the incidence of NTM infections has been increasing in recent years. Mycobacteroides abscessus (M. abscessus) is one of the most antimicrobial-resistant NTM; however, no reliable antibiotic regimen can be officially advocated. We evaluated the efficacy of clarithromycin in combination with various antimicrobial agents against the M. abscessus complex.ResultsTwenty-nine clinical strains of M. abscessus were isolated from various clinical samples. Of the isolates, 10 (34.5%) were of M. abscessus subsp. abscessus, 18 (62.1%) of M. abscessus subsp. massiliense, and 1 (3.4%) of M. abscessus subsp. bolletii. MICs of three antimicrobial agents (amikacin, imipenem, and moxifloxacin) were measured with or without clarithromycin. The imipenem-clarithromycin combination significantly reduced MICs compared to clarithromycin and imipenem monotherapies, including against resistant strains. The association between susceptibility of the M. abscessus complex and each combination of agents was significant (p = 0.001). Adjusted residuals indicated that the imipenem-clarithromycin combination had the synergistic effect (adjusted residual = 3.1) and suppressed the antagonistic effect (adjusted residual = − 3.1). In subspecies of M. abscessus complex, the association with susceptibility of M. abscessus subsp. massiliense was similarly statistically significant (p = 0.036: adjusted residuals of synergistic and antagonistic effect respectively: 2.6 and − 2.6). The association with susceptibility of M. abscessus subsp. abscessus also showed a similar trend but did not reach statistical significance.ConclusionOur data suggest that the imipenem-clarithromycin combination could be the recommended therapeutic choice for the treatment of M. abscessus complex owing to its ability to restore antimicrobial susceptibility.

Lack of significant differences between gastrointestinal tract microbial population structure of Helicobacter pylori-infected subjects before and 2years after a single eradication event.

According to recent estimates 80% of Latvian population is infected with Helicobacter pylori thus their susceptibility to numerous gastric tract diseases is increased. The 1st line H. pylori eradication therapy includes treatment with clarithromycin in combination with amoxicillin or metronidazole and a proton pump inhibitor. However, potential adverse events caused by such therapies to microbiome are insufficiently studied. This study aimed to evaluate the long-term effect of H. pylori eradication on human gastrointestinal tract (GIT) microbiome. The assessment of Hpylori eradication impact on GIT microbiome was done by analyzing 120 samples acquired from 60 subjects. Each individual was prescribed the following 10-day eradication regimen: Esomeprazolum 40mg, Clarithromycinum 500mg, and Amoxicillinum 1000mg, BID. Samples from each individual were collected before starting Hpylori eradication therapy, and 2years after the completion of the therapy in OC-Sensor (Eiken Chemical Co.) sample collection containers and stored at -86°C. Prior to DNA extraction, the samples were lyophilized, and total DNA was extracted using FastDNA Spin Kit for Soil. 16S V3 rRNA gene sequencing was done employing Ion Torrent PGM, and the obtained raw sequences were analyzed using vsearch and R (phyloseq, cluster packages). Alpha diversity measurements-observed OTUs, Chao1 and Shannon index did not differ significantly between the pre- and post-eradication states (two-tailed paired t test: P=.95; P=.71, P=.24, respectively). Unweighted and weighted UniFrac distances of beta diversity analysis indicated a non-specific pattern of sample clustering. Enterotype shift was observed for the majority of individuals comparing pre- and post-eradication study groups. Association analysis revealed that certain bacterial genera significantly correlated with age (eg, Dialister, Paraprevotella, Bifidobacterium), individual (eg, Thermotunica, Streptomyces, Faecalibacterium), and history of respiratory and/or allergic diseases (eg, Colinsella, Faecalibacterium). Redundancy analysis confirmed that the individual was a significant determinant of the subject's microbial community composition (ANOVA, 999 perm., P=.001) with the further lower impact of subject-specific medical history (eg, medication used as prescribed: P=.005, history of cardiovascular diseases: P=.005, history of respiratory, and/or allergic diseases: P=.015) and physiological (eg, age: P=.005, gender: P=.02) parameters. In the post-eradication study group, number of influential genera (n=260) was increased compared to the pre-eradication study group (n=209). Modest global differences at the community level exist between individuals before and after the eradication therapy; however, the microbiome structure is more related to the subject-specific parameters rather than by the eradication therapy itself.