Initial Development toward Non-Invasive Drug Monitoring via Untargeted Mass Spectrometric Analysis of Human Skin.

Drug monitoring is crucial for providing accurate and effective care; however, current methods (e.g., blood draws) are inconvenient and unpleasant. We aim to develop a non-invasive method for the detection and monitoring of drugs via human skin. The initial development toward this aim required information about which drugs, taken orally, can be detected via the skin. Untargeted liquid chromatography-mass spectrometry (LC-MS) was used as it was unclear if drugs, known drug metabolites, or other transformation products were detectable. In accomplishing our aim, we analyzed samples obtained by swabbing the skin of 15 kidney transplant recipients in five locations (forehead, nasolabial area, axillary, backhand, and palm), bilaterally, on two different clinical visits. Untargeted LC-MS data were processed using molecular networking via the Global Natural Products Social Molecular Networking platform. Herein, we report the qualitative detection and location of drugs and drug metabolites. For example, escitalopram/citalopram and diphenhydramine, taken orally, were detected in forehead, nasolabial, and hand samples, whereas N-acetyl-sulfamethoxazole, a drug metabolite, was detected in axillary samples. In addition, chemicals associated with environmental exposure were also detected from the skin, which provides insight into the multifaceted chemical influences on our health. The proof-of-concept results presented support the finding that the LC-MS and data analysis methodology is currently capable of the qualitative assessment of the presence of drugs directly via human skin

Dihydropteroate synthase gene mutations in Pneumocystis and sulfa resistance

Pneumocystis pneumonia (PCP) remains a major cause of illness and death in HIV-infected persons. Sulfa drugs, trimethoprim-sulfamethoxazole (TMP-SMX) and dapsone are mainstays of PCP treatment and prophylaxis. While prophylaxis has reduced the incidence of PCP, its use has raised concerns about development of resistant organisms. The inability to culture human Pneumocystis, Pneumocystis jirovecii, in a standardized culture system prevents routine susceptibility testing and detection of drug resistance. In other microorganisms, sulfa drug resistance has resulted from specific point mutations in the dihydropteroate synthase (DHPS) gene. Similar mutations have been observed in P. jirovecii. Studies have consistently demonstrated a significant association between the use of sulfa drugs for PCP prophylaxis and DHPS gene mutations. Whether these mutations confer resistance to TMP-SMX or dapsone plus trimethoprim for PCP treatment remains unclear. We review studies of DHPS mutations in P. jirovecii and summarize the evidence for resistance to sulfamethoxazole and dapsone

Prevalence and antimicrobial resistance of Salmonella in retail foods in northern China

A total of 387 retail meat, seafood and milk powder samples were collected from nine cities in northern China in 2005 and screened for the presence of Salmonella. Salmonella strains isolated were subjected to serotyping and antimicrobial susceptibility testing. Salmonella was isolated from 81 (20.9%, 81/387) samples and classified into 23 serotypes. The isolates were frequently resistant to sulfamethoxazole (86.4%), sulfamethoxazole/trimethoprim (48.1%), nalidixic acid (30.9%), tetracycline (19.8%), carboxybenzylpenicillin (17.3%), amoxicillin (17.3%) and ampicillin (16.0%). The multiple resistance (resistance to ≥ 3 antibiotics) was found in 29.6% (n = 24) isolates. Additionally, 4 isolates from chicken displayed the ACSSuTNx profile, resistant to ampicillin, chloramphenicol, streptomycin, sulfonamide, tetracycline and nalidixic acid, in particular, strain HBS084 showing the resistance to as many as 20 antibiotics. Salmonella from chicken showed the higher frequency of antimicrobial resistance. Our findings indicate that in northern China food products of animal origin can be a source of exposure for consumers to multiresistant Salmonella strain

In vitro activity of ceftazidime, ciprofloxacin, meropenem, minocycline, tobramycin and trimethoprim/sulfamethoxazole against planktonic and sessile Burkholderia cepacia complex bacteria

Objectives: The goal of the present study was to obtain a comprehensive overview of the bacteriostatic and bactericidal effects of six commonly used antibiotics on planktonic as well as on sessile Burkholderia cepacia complex cells. Methods: The bacteriostatic and bactericidal activities of ceftazidime, ciprofloxacin, meropenem, minocycline, tobramycin and trimethoprim/sulfamethoxazole were determined against 38 B. cepacia complex strains. MICs and minimal biofilm inhibitory concentrations (MBICs) were determined using a traditional broth microdilution method and a novel resazurin-based viability staining, respectively. The bactericidal effects of the investigated antibiotics (using antibiotic concentrations corresponding to 10 x MIC; except for tobramycin, for which a final concentration of 4 x MIC was tested) on stationary phase planktonic cultures and on 24-h-old biofilms were evaluated using conventional plate count methods. Results: Our results confirm the innate resistance of B. cepacia complex organisms to six first-line antibiotics used to treat infected cystic fibrosis patients. All antibiotics showed similar bacteriostatic activities against exponentially growing B. cepacia complex planktonic cells and freshly adhered sessile cells (4 h). In addition, most of the antibiotics showed similar bactericidal effects on stationary phase planktonic cultures and on young and older biofilms. Conclusions: Despite the general assumption that sessile cells show a decreased susceptibility to antibiotics, our data indicate similar bacteriostatic and bactericidal activity of six selected antibiotics against planktonic and sessile B. cepacia complex bacteria

Investigating the removal of some pharmaceutical compounds in hospital wastewater treatment plants operating in Saudi Arabia

The concentrations of 12 pharmaceutical compounds (atenolol, erythromycin, cyclophosphamide, paracetamol, bezafibrate, carbamazepine, ciprofloxacin, caffeine, clarithromycin, lidocaine, sulfamethoxazole and Nacetylsulfamethoxazol (NACS)) were investigated in the influents and effluents of two hospital wastewater treatment plants (HWWTPs) in Saudi Arabia. The majority of the target analytes were detected in the influent samples apart from bezafibrate, cyclophosphamide, and erythromycin. Caffeine and paracetamol were detected in the influent at particularly high concentrations up to 75 and 12 ug/L, respectively. High removal efficiencies of the pharmaceutical compounds were observed in both HWWTPs, with greater than 90 % removal on average. Paracetamol, sulfamethoxazole, NACS, ciprofloxacin, and caffeine were eliminated by between >95 and >99 % on average. Atenolol, carbamazepine, and clarithromycin were eliminated by >86 % on average. Of particular interest were the high removal efficiencies of carbamazepine and antibiotics that were achieved by the HWWTPs; these compounds have been reported to be relatively recalcitrant to biological treatment and are generally only partially removed. Elevated temperatures and high levels of sunlight were considered to be the main factors that enhanced the removal of these compounds

Successful Intra-peritoneal Antibiotic Therapy for Primary Abdominal Nocardiosis in an Immunocompetent Young Female Masquerading as Carcinoma Ovary

Nocardiosis is a common opportunistic infection in the immunocompromised and in patients with chronic debilitating diseases,e.g continuous ambulatory peritoneal dialysis (CAPD) patients. Primary abdominal nocardiosis is rare and is indeed a very rare infection in immunocompetent persons. Only two cases have been reported in immunocompetent patients so far and this may be third case to the best of our knowledge and first in India. About 11 cases have been reported in CAPD patients and AIDS patients.We report a case of Nocardiosis in an immunocompetent young female who presented with an abdomino-pelvic mass masquerading as carcinoma ovary.After initial resistance to various antibiotics, she responded to intraperitoneal and oral linezolid and oral ciprofloxacin

Predatory Bacteria: A Potential Ally against Multidrug-Resistant Gram-Negative Pathogens

Multidrug-resistant (MDR) Gram-negative bacteria have emerged as a serious threat to human and animal health. Bdellovibrio spp. and Micavibrio spp. are Gram-negative bacteria that prey on other Gram-negative bacteria. In this study, the ability of Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus to prey on MDR Gram-negative clinical strains was examined. Although the potential use of predatory bacteria to attack MDR pathogens has been suggested, the data supporting these claims is lacking. By conducting predation experiments we have established that predatory bacteria have the capacity to attack clinical strains of a variety of ß-lactamase-producing, MDR Gram-negative bacteria. Our observations indicate that predatory bacteria maintained their ability to prey on MDR bacteria regardless of their antimicrobial resistance, hence, might be used as therapeutic agents where other antimicrobial drugs fail. © 2013 Kadouri et al

Removal of sulfamethoxazole and sulfapyridine by carbon nanotubes in fixed-bed columns

Sulfamethoxazole (SMX) and sulfapyridine (SPY), two representative sulfonamide antibiotics, have gained increasing attention because of the ecological risks these substances pose to plants, animals, and humans. This work systematically investigated the removal of SMX and SPY by carbon nanotubes (CNTs) in fixed-bed columns under a broad range of conditions including: CNT incorporation method, solution pH, bed depth, adsorbent dosage, adsorbate initial concentration, and flow rate. Fixed-bed experiments showed that pH is a key factor that affects the adsorption capacity of antibiotics to CNTs. The Bed Depth Service Time model describes well the relationship between service time and bed depth and can be used to design appropriate column parameters. During fixed-bed regeneration, small amounts of SMX (3%) and SPY (9%) were irreversibly bonded to the CNT/sand porous media, thus reducing the column capacity for subsequent reuse from 67.9 to 50.4 mg g−1 for SMX and from 91.9 to 72.9 mg g−1 for SPY. The reduced column capacity resulted from the decrease in available adsorption sites and resulting repulsion (i.e., blocking) of incoming antibiotics from those previously adsorbed. Findings from this study demonstrate that fixed-bed columns packed with CNTs can be efficiently used and regenerated to remove antibiotics from water

Oxidative stress responses and cellular energy allocation changes in microalgae following exposure to widely used human antibiotics

The individual effect of four human antibiotics on the microalgae Raphidocelis subcapitata was investigated following a 120-h exposure. The effects were assessed by analyzing growth, and biochemical parameters related with: 1) antioxidant capacity and oxidative damage by measuring superoxide dismutase (SOD) activity and lipid peroxidation (LPO) levels; and 2) cellular energy allocation (CEA) by quantifying the content in energy reserves, which represents the energy available (Ea), and the electron transport system activity that represents a measure of oxygen and cellular energy consumption (Ec). Growth yield inhibitory concentrations of sulfamethoxazole (18-30%), clarithromycin (28.7%), ciprofloxacin (28%) and erythromycin (17-39%) were found to elicit a considerable increase in Ec, thereby causing a significant decrease in the CEA. The elevated Ec can be a result of the need to respond to oxidative stress occurring under those conditions given the significant increase in SOD activity at these levels. For sulfamethoxazole, erythromycin and ciprofloxacin, the antioxidant responses do not seem to be enough to cope with the reactive oxygen species and prevent oxidative damage, given the elevated LPO levels observed. A stimulatory effect on growth yield was observed (up to 16%) at ciprofloxacin lowest concentration, which highly correlated with the increase in CEA. Based on the no observed effect concentration (NOECs) and/or effective concentration (EC10) results, Ec, SOD and CEA were more sensitive than the classical endpoint of growth rate for all the tested antibiotics. By revealing the antibiotic stress effects in R. subcapitata at the cellular level, this study suggests CEA as a more reliable indicator of the organisms' physiological status.info:eu-repo/semantics/publishedVersio