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C. difficile

Metronidazole therapy for intra-abdominal infections . Complicated and serious intra-abdominal infections frequently occur in clinical medicine, and their treatment requires advanced hospital resources. The management of intra-abdominal infections has developed significantly during the past 10 years. Proper use of antimicrobial agents is mandatory. New guidelines for the diagnosis and management of complicated intra-abdominal infections in adults and children have been written by the Infectious Diseases Society of America, the Surgical Infection Society, and the Pediatric Infectious Disease Society and are now under review (J. S. Solomkin, personal communication) ( Table 2 ). These guidelines separate the infections into 2 categories: community-acquired and health care-associated infections. For moderate community-acquired infections in adults, metronidazole in combination with cefazolin, cefuroxime, ceftriaxone, or a quinolone is recommended. Metronidazole together with ceftazidine or cefepime or single-drug therapy with carbapenems and piperacillin-tazobactam is suggested for the management of severe community-acquired intra-abdominal infection. For children, metronidazole in combination with cefuroxime or ceftriaxone is recommended. An alternative agent is cefoxitin. Oral metronidazole in combination with oral second- or third-generation cephalosporin may also be effective. Health care-associated intra-abdominal infections are often caused by more-drug-resistant microorganisms, such as Staphylococcus aureus , enterococci, Pseudomonas aeruginosa, Acinetobacter baumanni, Klebsiella species, Enterobacter species, Proteus species, and Candida species. Multidrug treatment, based on microorganism susceptibility patterns, is recommended for these infections.

Convalescing patients with complicated intra-abdominal infections can often be treated with oral antimicrobials. For adults, metronidazole in combination with a fluoroquinolone or trimethoprim-sulfamethoxazole may be effective. Oral metronidazole in combination with an oral second- or third-generation cephalosporin can be provided to children.

The favorable efficacy of metronidazole for the management of intra-abdominal infections was recently indicated by Matthaiou et al [ 8 ] in a meta-analysis comparing treatment with metronidazole and ciprofloxacin with treatment with broad-spectrum β-lactam antibiotics. The authors found that, for patients with intra-abdominal infections, treatment with metronidazole and ciprofloxacin was associated with greater success than was treatment with β-lactam agents. Recently, Wang et al [ 9 ] showed that 1 g of metronidazole given intravenously once daily for treatment of severe intra-abdominal and pelvic infections has pharmacokinetic and pharmacoeconomic advantages over treatment administered every 6–8 h.

Metronidazole is active against a variety of protozoa and bacteria. It enters the cell as a prodrug by passive diffusion and is activated in either the cytoplasm of the bacteria or specific organelles in the protozoa, whereas drug-resistant cells are deficient in drug activation. The metronidazole molecule is converted to a short-lived nitroso free radical by intracellular reduction, which includes the transfer of an electron to the nitro group of the drug. This form of the drug is cytotoxic and can interact with the DNA molecule. The actual mechanism of action has not yet been fully elucidated but includes the inhibition of DNA synthesis and DNA damage by oxidation, causing single-strand and double-strand breaks that lead to DNA degradation and cell death. The activated reduced metronidazole molecule binds nonspecifically to bacterial DNA, inactivating the organism's DNA and enzymes and leading to a high level of DNA breakage, with immediate action of the drug but no cell lysis [ 10 , 11 ]. Aerobic cells lack electron-transport proteins with sufficient negative redox potential; therefore, the drug is active against only bacteria with anaerobic metabolisms, even though the drug is effective against some microaerophils, such as H. pylori. In addition, reoxidation can occur in the presence of molecular oxygen and can convert the compound back to its original inactive form [ 12 ]. Electron donors involved in the reduction process vary, depending on the organism. In anaerobic bacteria, the electron acceptors flavodoxin and ferredoxin, which receive electrons from the pyruvate-ferredoxin oxireductase complex, play important roles, although other enzymes and electron transfer components may also be involved in the process. Each of these acceptors has a reduction potential lower than that of the metronidazole molecule and will thereby donate its electrons to the drug [ 12 ]. In H. pylori , a separate mechanism seems to be involved in metronidazole susceptibility that includes a 2-electron transfer step in the reduction of the compound using an oxygen-insensitive nitroreductase (rdxA). Metronidazole-resistant clones are typically mutated in the rdxA gene [ 10 , 13 ].

Fig 3. Comparison of cropped true colour composite images from Pleiades-1B satellite and DJI-Phantom-2 drone.

(A-B) The images for mangrove vegetation mapping at the Setiu Wetland. Red boxes show the zoomed-in subsets of–(C) Pleiades-1B and, (D) DJI-Phantom-2 drone, revealing mangrove and non-mangrove details on the ground at 50cm and 5cm spatial resolutions respectively.

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Table 2. Spatial, spectral, radiometric and temporal resolutions of the Pleiades-1B satellite and DJI-Phantom-2 drone images (source for Pleiades-1B information: Pleiades user guide [ Regular Fit Jeans 32inches Black Vero Moda Ost Release Dates Top Quality Online Fast Delivery kQ8VRtezZU
]).

https://doi.org/10.1371/journal.pone.0200288.t002

The cost of the DJI-Phantom-2 drone (with an RGB SJ4000 camera) used in this study was 950USD (April 2015). In addition, the cameras and other accessories (gimbal, GPS logger, batteries) cost 1003USD. Together with the fieldwork expenses of 500USD, the total budget spent was 2453USD. On the other hand, the Pleiades-1B imagery was procured for 1750USD. Out of the two months’ fieldwork, two weeks were focused on the aerial photos acquisition, and obtained 19 composite (RGB, IR and DEM) images, covering area of 1.81km 2 ( Fig 4 ). If the mangrove surface area being covered in the present aerial photos is considered, then the drone data acquisition cost was ca . 1355USD per km 2 (2453USD ÷ 1.81km 2 ), which is more expensive than the Pleiades-1B satellite data (17.5USD per km 2 ). The Pleiades data is still economical, even after adding the cost of present fieldwork expenses (22.5USD per km 2 ). Although each of our 15 minutes drone flights, corresponding to the average battery run-time at a given speed/altitude, typically covered 0.12km 2 , the parallax cropping reduced it to 0.09–0.11km 2 ( Fig 4 ).

Fig 4. Visual representation of the spatial coverage of Pleiades-1B and DJI-Phantom-2 drone data sets.

While new tasking/purchasing order of Pleiades images requires at least 100km 2 coverage, the archived data of each image is available for a minimum of 25 km 2 . A drone is expected to work efficiently (if it does not crash or have technical problems) for 500 flights. If an efficient drone flight for 15 min (corresponding to average battery run-time) can cover approximately 0.1 km 2 , the total drone flights would be able to cover ca . 50 km 2 . However, with an improved battery run-time of up to 20 min these days, the same drone can deliver aerial photos of an area covering up to 75 km 2 (box dimensions are arbitrary, and the colours are for visualization purposes only).

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