Vabomere
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Vabomere
Meropenem/vaborbactam, sold under the brand name Vabomere among others, is a combination medication used to treat complicated urinary tract infections, complicated abdominal infections, and hospital-acquired pneumonia. It contains meropenem, a β-lactam antibiotic, and vaborbactam Vaborbactam (INN) is a non-β-lactam β-lactamase inhibitor discovered by Rempex Pharmaceuticals, a subsidiary of The Medicines Company. While not effective as an antibiotic by itself, it restores potency to existing antibiotics by inhibiting th ..., a β-lactamase inhibitor. It is given by injection into a vein. Common side effects include headache, inflammation at the site of injection, nausea, diarrhea, liver inflammation, and low blood potassium. Severe side effects may include anaphylaxis, seizures, and ''Clostridium difficile''-associated diarrhea. It is unclear if use during pregnancy is safe. Meropenem works by blocking the construction of the bacterial cell wall while vaborbac ...
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Vaborbactam
Vaborbactam (INN) is a non-β-lactam β-lactamase inhibitor discovered by Rempex Pharmaceuticals, a subsidiary of The Medicines Company. While not effective as an antibiotic by itself, it restores potency to existing antibiotics by inhibiting the β-lactamase enzymes that would otherwise degrade them. When combined with an appropriate antibiotic it can be used for the treatment of gram-negative bacterial infections. In the United States, the combination drug meropenem/vaborbactam (Vabomere) is approved by the Food and Drug Administration for complicated urinary tract infections and pyelonephritis. Biochemistry Vaborbactam is a boronic acid β-lactamase inhibitor with a high affinity for serine β-lactamases, including ''Klebsiella pneumoniae'' carbapenemase (KPC). Vaborbactam inhibits a variety of β-lactamases, exhibiting a 69 nM Ki against the KPC-2 carbapenemase and even lower inhibition constants against CTX-M-15 and SHV-12. Boronic acids are unusual in their abili ...
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β-lactam Antibiotic
β-lactam antibiotics (beta-lactam antibiotics) are antibiotics that contain a beta-lactam ring in their chemical structure. This includes penicillin derivatives (penams), cephalosporins and cephamycins (cephems), monobactams, carbapenems and carbacephems. Most β-lactam antibiotics work by inhibiting cell wall biosynthesis in the bacterial organism and are the most widely used group of antibiotics. Until 2003, when measured by sales, more than half of all commercially available antibiotics in use were β-lactam compounds. The first β-lactam antibiotic discovered, penicillin, was isolated from a rare variant of ''Penicillium notatum'' (since renamed ''Penicillium chrysogenum)''. Bacteria often develop resistance to β-lactam antibiotics by synthesizing a β-lactamase, an enzyme that attacks the β-lactam ring. To overcome this resistance, β-lactam antibiotics can be given with β-lactamase inhibitors such as clavulanic acid. Medical use β-lactam antibiotics are indicated for ...
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Pregnancy
Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but can also occur through assisted reproductive technology procedures. A pregnancy may end in a live birth, a miscarriage, an induced abortion, or a stillbirth. Childbirth typically occurs around 40 weeks from the start of the last menstrual period (LMP), a span known as the gestational age. This is just over nine months. Counting by fertilization age, the length is about 38 weeks. Pregnancy is "the presence of an implanted human embryo or fetus in the uterus"; implantation occurs on average 8–9 days after fertilization. An '' embryo'' is the term for the developing offspring during the first seven weeks following implantation (i.e. ten weeks' gestational age), after which the term ''fetus'' is used until birth. Signs an ...
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Beta-lactamase Inhibitors
Beta-lactamases, (β-lactamases) are enzymes () produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems (ertapenem), although carbapenems are relatively resistant to beta-lactamase. Beta-lactamase provides antibiotic resistance by breaking the antibiotics' structure. These antibiotics all have a common element in their molecular structure: a four-atom ring known as a beta-lactam (β-lactam) ring. Through hydrolysis, the enzyme lactamase breaks the β-lactam ring open, deactivating the molecule's antibacterial properties. Beta-lactam antibiotics are typically used to target a broad spectrum of gram-positive and gram-negative bacteria. Beta-lactamases produced by gram-negative bacteria are usually secreted, especially when antibiotics are present in the environment. Structure The structure of a ''Streptomyces'' serine β-lactamase (SBLs) is given by . The alpha-beta fold ...
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Combination Antibiotics
In mathematics, a combination is a selection of items from a set that has distinct members, such that the order of selection does not matter (unlike permutations). For example, given three fruits, say an apple, an orange and a pear, there are three combinations of two that can be drawn from this set: an apple and a pear; an apple and an orange; or a pear and an orange. More formally, a ''k''-combination of a set ''S'' is a subset of ''k'' distinct elements of ''S''. So, two combinations are identical if and only if each combination has the same members. (The arrangement of the members in each set does not matter.) If the set has ''n'' elements, the number of ''k''-combinations, denoted as C^n_k, is equal to the binomial coefficient \binom nk = \frac, which can be written using factorials as \textstyle\frac whenever k\leq n, and which is zero when k>n. This formula can be derived from the fact that each ''k''-combination of a set ''S'' of ''n'' members has k! permutations so P^n ...
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Carbapenem Antibiotics
Carbapenems are a class of very effective antibiotic agents most commonly used for the treatment of severe bacterial infections. This class of antibiotics is usually reserved for known or suspected multiple drug resistance, multidrug-resistant (MDR) bacterial infections. Similar to penicillins and cephalosporins, carbapenems are members of the beta lactam class of antibiotics, which kill bacteria by binding to penicillin-binding proteins, thus inhibiting bacterial cell wall synthesis. However, these agents individually exhibit a broader spectrum of activity compared to most cephalosporins and penicillins. Furthermore, carbapenems are typically unaffected by emerging antimicrobial resistance, antibiotic resistance, even to other beta-lactams. Carbapenem antibiotics were originally developed at Merck & Co. from the carbapenem thienamycin, a naturally derived product of ''Streptomyces cattleya''. Concern has arisen in recent years over increasing rates of resistance to carbapenems, as ...
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Pyelonephritis
Pyelonephritis is inflammation of the kidney, typically due to a bacterial infection. Symptoms most often include fever and flank tenderness. Other symptoms may include nausea, burning with urination, and frequent urination. Complications may include pus around the kidney, sepsis, or kidney failure. It is typically due to a bacterial infection, most commonly ''Escherichia coli''. Risk factors include sexual intercourse, prior urinary tract infections, diabetes, structural problems of the urinary tract, and spermicide use. The mechanism of infection is usually spread up the urinary tract. Less often infection occurs through the bloodstream. Diagnosis is typically based on symptoms and supported by urinalysis. If there is no improvement with treatment, medical imaging may be recommended. Pyelonephritis may be preventable by urination after sex and drinking sufficient fluids. Once present it is generally treated with antibiotics, such as ciprofloxacin or ceftriaxone. Thos ...
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Minimum Inhibitory Concentration
In microbiology, the minimum inhibitory concentration (MIC) is the lowest concentration of a chemical, usually a drug, which prevents visible growth of a bacterium or bacteria. MIC depends on the microorganism, the affected human being (in vivo only), and the antibiotic itself. It is often expressed in micrograms per milliliter (μg/mL) or milligrams per liter (mg/L). The MIC is determined by preparing solutions of the chemical in vitro at increasing concentrations, incubating the solutions with separate batches of cultured bacteria, and measuring the results using agar dilution or broth microdilution. Results have been graded into susceptible (often called sensitive), increased exposure, or resistant to a particular antimicrobial by using a breakpoint. Breakpoints are agreed upon values, published in guidelines of a reference body, such as the U.S. Clinical and Laboratory Standards Institute (CLSI), the British Society for Antimicrobial Chemotherapy (BSAC) or the European Committee ...
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Food And Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food safety, tobacco products, caffeine products, dietary supplements, Prescription drug, prescription and Over-the-counter drug, over-the-counter pharmaceutical drugs (medications), vaccines, biopharmaceuticals, blood transfusions, medical devices, electromagnetic radiation emitting devices (ERED), cosmetics, Animal feed, animal foods & feed and Veterinary medicine, veterinary products. The FDA's primary focus is enforcement of the Federal Food, Drug, and Cosmetic Act (FD&C), but the agency also enforces other laws, notably Section 361 of the Public Health Service Act, as well as associated regulations. Much of this regulatory-enforcement work is not d ...
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Piperacillin/tazobactam
Piperacillin/tazobactam, sold under the brand name Zosyn among others, is a combination medication containing the antibiotic piperacillin and the β-lactamase inhibitor tazobactam. The combination has activity against many Gram-positive and Gram-negative bacteria including '' Pseudomonas aeruginosa''. It is used to treat pelvic inflammatory disease, intra-abdominal infection, pneumonia, cellulitis, and sepsis. It is given by injection into a vein. Common adverse effects include headache, trouble sleeping, rash, nausea, constipation, and diarrhea. Serious adverse effects include ''Clostridium difficile'' infection and allergic reactions including anaphylaxis. Those who are allergic to other β-lactam are more likely to be allergic to piperacillin/tazobactam. Use in pregnancy or breastfeeding appears to generally be safe. It usually results in bacterial death through blocking their ability to make a cell wall. Piperacillin/tazobactam was approved for medical u ...
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WHO Model List Of Essential Medicines
The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health system. The list is frequently used by countries to help develop their own local lists of essential medicines. , more than 155 countries have created national lists of essential medicines based on the World Health Organization's model list. This includes both developed and developing countries. The list is divided into core items and complementary items. The core items are deemed to be the most cost-effective options for key health problems and are usable with little additional health care resources. The complementary items either require additional infrastructure such as specially trained health care providers or diagnostic equipment or have a lower cost–benefit ratio. About 25% of items are in the complementary list. Some medicatio ...
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β-lactamase
Beta-lactamases, (β-lactamases) are enzymes () produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems ( ertapenem), although carbapenems are relatively resistant to beta-lactamase. Beta-lactamase provides antibiotic resistance by breaking the antibiotics' structure. These antibiotics all have a common element in their molecular structure: a four-atom ring known as a beta-lactam (β-lactam) ring. Through hydrolysis, the enzyme lactamase breaks the β-lactam ring open, deactivating the molecule's antibacterial properties. Beta-lactam antibiotics are typically used to target a broad spectrum of gram-positive and gram-negative bacteria. Beta-lactamases produced by gram-negative bacteria are usually secreted, especially when antibiotics are present in the environment. Structure The structure of a ''Streptomyces'' serine β-lactamase (SBLs) is given by . The alpha-beta fold ...
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