Antibiotic Doripenem - Coursework Example

A SERIES OF QUESTIONS ABOUT THE ANTIBIOTIC DORIPENEM By The antibiotic doripenem (Doribax®) is recommended for use in patients with complicated urinary tract infections, including pyelonephritis. Describe in detail what pyelonephritis is and the likely causative micro-organism(s)? Pyelonephritis is a kind of UTI (urinary tract infection) that impacts one or all the kidneys. Acute pyelonephritis denotes an abrupt and severe kidney illness (Sweet and Gibbs 2009). Pyelonephritis condition makes the kidneys to enlarge and can lastingly damage them. If not check early enough can even be life threatening. It is imperative to recognise the signs so one can seek early medical attention. In case of repeated or persistent attacks, the state is known as chronic pyelonephritis. The chronic type of the state is rare. Symptoms typically emerge within 24 to 36hrs after the infection starts (Elsevier Inc. 2012). They may be adverse in youngsters and the elderly than witnessed in non-elderly adults and adolescents (Sweet and Gibbs 2009). However, regular symptoms comprise the following: a fever of over one hundred and two degrees abdominal, side, back, or groin pain Burning or painful urination (Elsevier Inc. 2012). Acute illness of the parenchyma or renal pelvis Acute pyelonephritis is normally due to rising infection; in simple cases the aberrant organism is typically Escherichia coli at 75% (Elsevier Inc. 2012). Individuals with pyelonephritis and acute concomitant sickness have severe tissue infection and are in danger of bacteremia; advantage is realised due to early admission for discussion and concentrated parenteral antimicrobial treatment (Klostranec and Kolin 2012). The infection normally begins from the lower urinary tract as a UTI. Bacteria penetrate one’s body through urethra and start to multiply and increase up the track. From the bladder, the microorganisms propagate up through the urethras to the kidneys. Bacteria such as Escherichia coli, usually acknowledged as E. coli, often ground the contagion. But any severe infectivity in the blood stream can extend to the kidneys and lead to acute pyelonephritis (Madara and Pomarico-Denino 2008). Chronic pyelonephritis is more frequent in youngsters or in individuals with urinary obstructions. When the urinary region is of abnormal shape or size, it is more probable that illness can cause acute pyelonephritis. Any person with persistent kidney stones or other kidney or bladder situation is also at danger. At any time there is a problem that interrupts the normal run of urine there is a bigger threat of sensitive pyelonephritis (Madara and Pomarico-Denino 2008). Causative micro organisms Ascending urinary tract infection: 75% of pyelonephritis circumstances are because of E. coli; ten to fifteen percent are caused by additional Gram-negative rods, Enterobacter, Proteus, Klebsiella; others consist of Pseudomonas, Citrobacter and Serratia (Schlossberg 2008). Gram-positive agents comprise Enterococcus faecalis and, not common, Staphylococcus aureus anaerobes Other infecting bacteria may comprise Leptospira, Salmonella, Chlamydia Fungal agents, Mycoplasma, particularly Candida spp., are observed in immune weakling patients and individuals with diabetes (Elsevier Inc. 2012). In travellers, the likelihood of tropical disease and Echinococcus must be taken into consideration (Schlossberg 2008). 2. Describe the antimicrobial action of doripenem. Include in your answer details of bacterial resistance mechanisms towards this class of antimicrobials. Antimicrobial fight has been influencing the discipline of communicable diseases since the detection of penicillin (Mayers 2008). A number of the progresses in antimicrobial drug growth have result from efforts to handle ever-evolving processes of resistance that leave existing agents out-of-date, thus causing the search for pioneering molecules that guarantee to be more influential and more flexible. Anticipation for a magic all-inclusive antimicrobial process has been approved. However, the quantity of fresh antimicrobial agents in the medicine mechanism is a small portion of what it formed to control. Doripenem is a fresh 1-β-methyl carbapenem with precise side series substitutions improving activity against no fermentative gram-negative bacilli (Grayson et al 2010). It is a carbapenem antibiotic that comprises a wide variety of gram-negative and gram-positive pathogens. In vitro analysis, the study has given insight into certain characteristics of doripenems action profile that may have precise relevance in the clinical environment. Data concerning the intrinsic practices of doripenem show that this agent encompasses a wide range of pathogenic microbes (Grayson et al 2010). Similar to other carbapenems, it is taken to be active against most segregates of gram-negative and gram-positive pathogens including anaerobes and aerobes, with the exemption of Burkholderia cepacia, Stenotrophomonas maltophilia, methicillin-resistant, Staphylococcus aureus, and Enterococcus faecium (Grayson et al 2010). A further detailed assessment of the available data illustrates that doripenem gives a broad range of antimicrobial exposure and also moderately affect accomplishment against gram-negative organisms that comprise an augmented potential for the expansion of drug resistance, like P. aeruginosa, Acinetobacter organism, and species of the Enterobacteriaceae units. The in vitro action of doripenem against clinically pertinent gram-negative and gram-positive pathogens has been measured in available studies, counting two that have permitted direct assessment of the in vitro activity outline of doripenem compared with those of both meropenem and imipenem (Mayers 2008). MDR (Multi-drug-resistant) bacteria have many resistance mechanisms commonly based on mobile resistance species, which can boost resistance to categories of antibiotics within and flanked by bacterial type. Classification of these bacteria and epidemics influenced by these MDR pathogens are growing in capacity. Doripenem forms a new original 1-β-methyl carbapenem. The carbapenem category was started by the expansion of imipenem during 1985 and extended by the enclosure of meropenem during1996 upgrade and recent by the extra ertapenem (Grayson et al 2010). Carbapenem antibiotics are organism wall fusion inhibitors and fit in to the β-lactam relatives of antibiotics. Bacterial resistance mechanisms that influence doripenem comprise drug inactivation that is caused by carbapenem-hydrolyzing organisms, mutant or needed by PBPs, reduced outer casing permeability and energetic efflux (Mayers 2008). Doripenem is steady to hydrolysis by generally beta-lactamases, comprising cephalosporinases and penicillinases and generated by Gram-negative and Gram-positive bacteria, with the exemption of carbapenem hydrolyzed beta-lactamases. Even though cross-resistance may happen, some separates resistant to other carbapenems could be susceptible to doripenem (Mayers 2008). Do not exceed this page – PTO 3. Describe the chemistry of doripenem (Doribax®) and explain how its structure confers antimicrobial activity. In comparison to amoxicillin, outline the unique chemical features of doripenem. The New Delhi metallo--lactamase (NDM-1) from K. pneumoniae is highly efficient in the inactivation of doripenem. Briefly discuss the properties of NDM-1 and the mechanism of doripenem inactivation. The chemistry of doripenem is structured by beta agents. The structure confers to antimicrobial activity since the agents are structured identically. Doripenem is a beta-lactam antibiotic mechanism fitting in to the carbapenem cluster, with a wide spectrum of bacterial susceptibility comprising both gram-negative and gram-positive bacteria. In vivo, doripenem restrains the fusion of cell walls by fixing itself to PBPs known as penicillin-binding proteins (Nurses Drug Handbook 2013). Broad-spectrum actions attached with constancy to extended-spectrum β-lactamases (ESBLs) and AmpC makes the doripenems a tremendously attractive group of antibiotics for auxiliary development. An additional benefit is so as to carbapenems, different extended-spectrum cephalosporin; do not choose AmpC-derepressed mutants as of inducible groups (Acton 2012). MDR bacteria are definite as non-vulnerability to one or extra antimicrobials on three or additional antimicrobial categories, while damages that are non-susceptible to every antimicrobials, are categorised as severe drug-defiant strains. MDR bacteria encompass a considerable influence on mortality, hospital residence and associated-expenses. The cephalosporin category of antimicrobial component is recognized for its wide spectrum of activity, established efficiency and favourable security profile, making it the largely commonly recommended class of antimicrobials (Acton 2012). Doripenem is a beta-lactam antibiotic while amoxicillin and Ampicillin are active against largely strains of Listeria, Proteus mirabilis, and non–beta-lactamase generates sprains of Haemophilus influenza; however, are immobile against the majority of gram-negative pathogens (Acton 2012). All drugs are effectual against Enterococcus faecalis and penicillin-susceptible pneumococcus; however, ampicillin-resistant E faecalis has materialized. Enterococcus faecium is expected to be opposed to piperacillin and ampicillin. It is noted that NDM-1 from K. pneumoniae is efficient in the inactivation of doripenem. The following properties of New Delhi metallo-β-lactamase provide the reason and causes. NDM-1 is a new broad spectrum carbapenemase with capability to make inactive all β-lactams apart from aztreonam (Acton 2012). Nevertheless, most of the New Delhi metallo-β-lactamase producers also generate aztreonam hydrolysing-β-lactamases thus making available pathogens completely resistant to every β-lactams. The bla(NDM-1) genetic material sets a 27.5 kDa protein containing 269 amino acids. It distributes very little individuality with erstwhile metallo-β-lactamases (Acton 2012). Utmost identity has been experiential to VIM-1/VIM-2 at 32.4%. Doripenem applies its bactericidal action by restraining bacterial cell partition biosynthesis. Doripenem does not stimulate numerous necessary PBPs (penicillin-binding proteins) resultant in inhibition of cell wall fusion with ensuing cell death. In P. aeruginosa and E. coli, doripenem combines to PBP 2 that is concerned in the preservation of cell shape, also to PBPs three and four (Nelson and Williams 2014). Bacterial fighting mechanisms that influence doripenem comprise drug inactivation caused by carbapenem-hydrolyzing mechanism, mutant or obtained PBPs, reduced outer membrane permeability and energetic efflux. Doripenem is steady to hydrolysis by mainly beta-lactamases, counting cephalosporinases and penicillinases generated by Gram-negative and Gram-positive bacteria, with the exemption of carbapenem hydrolyzing β-lactamases. Eeven though cross-resistance may happen, some segregates resistant to other carbapenems may be vulnerable to doripenem (Nelson and Williams 2014). Bacterial resistance mechanisms that consequence doripenem comprise active substance inactivation by carbapenem-hydrolysing mutants, mutant or attained PBPs, abridged outer casing permeability and lively efflux (Mayers 2008). Doripenem is stable to hydrolysis by the majority beta-lactamases, counting cephalosporinases and penicillinases produced by gram-negative and gram-positive bacteria, with the exemption of comparatively rare carbapenem hydrolysing beta-lactamases. Genes resistant to other carbapenems accomplish generally eloquent co-resistance to doripenem. It is also necessary to analyze that Methicillin-resistant staphylococci must always be considered as opposing to doripenem. As with additional antimicrobial agents, counting carbapenems such as doripenem has been revealed to choose for resistant bacterial strains (Mayers 2008). Efficient avoidance of the increase of NDM-1 producers needs a rapid screening system that can sense NDM-1 producers as settlers, mostly in the gastrointestinal zone, when the victim patient is divulged to any health care amenity. It has been discovered that have shown just that the show culture average ChromID ESBL culture media (bioMérieux) comprising cefpodoxime regarded as a selector, which is regularly applied to screen for ESBL (extended-spectrum β-lactamase) producers, may also be applied to detect carbapenemase-generating Enterobacteriaceae (Nelson and Williams 2014). 4. You are required to design a new doripenem analogue with antibacterial activity that is equivalent or comparable to doripenem. e-Draw the chemical structure of your doripenem analogue and provide a brief explanation of why your analogue would display clinically effective antibacterial activity. To design a new doripenem analogue with antibacterial activity that is equivalent or comparable to doripenem, it is essential to consider the current type so as to analyze and devise chemical structure to design. Doripenem (S-4661), a fresh parenteral carbapenem, got tested using participants more than 250 clinical mutants, transconjugants of Enterobacteriaceae, and isolates, and Acinetobacter spp., chosen or imitative for their β-lactamase appearance description (Gahart and Nazareno 2013). Imipenem, ertapenem and meropenem were experienced as comparators, the length of with piperacillin-tazobactam and cephalosporins by using nationwide group for Clinical Laboratory principles agar dilution method. Doripenem MICs applicable varied from 0.03 - 0.25 μg/ml for Klebsiella isolates, irrespective of the availability of ESBLs or hyperproduced K1 β-lactamase or plasmid-mediated AmpC. Likewise, MICs of doripenem for both and -derepressed Enterobacter and AmpC-inducible isolates applied comprises 0.06 to 0.5 μg/ml. ESBL construction does not increase the MICs of doripenem for Escherichia coli transconjugants, also analyzes with known appearance mutants established that nor inducible nor miserable AmpC β-lactamase appearance was defensive in Citrobacter freundii, Enterobacter cloacae, Morganella morganii or Serratia marcescens (Gahart and Nazareno 2013). E-diagram of suggested doripenem analogue. The designed chemical structure of doripenem analogue introduces enhancement of components to analyze provide a different analogue Doripenem shows broad-spectrum action against gram-negative and gram-positive bacteria both in vivo and in vitro. Like fresh carbapenems, it has a trans-designed 6-hydroxyethyl, and similar to ertapenem and meropenem, however, not imipenem, has a 1-β-methyl component, which defends against hydrolysis by renal dehydropeptidase I. The constituents are related to meropenem, however, are extra polar, including a free amino group (Gahart and Nazareno 2013). 5. Doripenem is currently only available for IV infusion. Assume you are working for a pharmaceutical company and have been tasked with designing an oral liquid formulation. Describe the process of designing this new formulation. Use referenced information on the physical and chemical properties of doripenem to justify your design decisions. If important properties are unknown, describe how you would experimentally obtain the information you need. Oral liquid formation Brand Name: PrDORIBAX*; Medicinal Ingredient: Doripenem monohydrate; Manufacturer/Sponsor:Janssen-Ortho Inc.; International Non-proprietary Name: Doripenem monohydrate; Dosage form: Powder for solution; Strength:500 mg/vial; Drug Identification Number (DIN): 32332906; Route of Administration: Intravenous (IV); and Submission Type and Control Number: New Drug Submission; Therapeutic Classification: Antibacterial agent; and Control Number: 113640 (Brusch 2012). As an employee in a pharmaceutical company the following will be a process of designing a new formation of doripenem. The above description provides the physical and chemical properties of the doripenem as indicated on the bottle. This is a confirmation that the properties are known (Golightly 2013). Doribax is reconstituted and then later diluted prior to infusion. Reconstitution of 500 mg dose of doripenem solution for infusion applying the 500 mg vial. The first step is to add 10 ml of sterile cooled water for injections or 9 mg/ml (0.9%) sodium chloride solvent for injection to available 500 mg vial and shake the solution well to create a suspension. After that it is necessary to inspect the suspension visually for strange substance (Golightly 2013). Note: the solution is not for straight infusion. After making sure that no foreign materials are available in solution, next step is to withdraw the suspension utilizing a syringe and a sterile needle and add the suspension to an infusion container containing 100 ml of either dextrose 50 mg/ml (5%) solution or sodium chloride 9 mg/ml (0.9%) solution for injection and merge to absolute dissolution. Infuse the entire solution to provide a 500 mg dosage of doripenem (Golightly 2013). Depending on the patient’s condition it is necessary to have dosage that can fit all the categories of patients. This is why it is necessary to constitute 250 mg dose of solution for infusion applying the 500 mg vial. The first step is the same with the first suspension. Add 10 ml of sterile cooled water for injections or 9 mg/ml (0.9%) sodium chloride solvent for injection to available 500 mg vial and shake the solution well to create a suspension (CHMP 2010). After that it is necessary to inspect the suspension visually for strange substance. Note: the solution is not for straight infusion (Golightly 2013). Then withdraws the suspension utilizing a syringe and a sterile needle and add the suspension to an infusion container containing 100 ml of either dextrose 50 mg/ml (5%) solution or sodium chloride 9 mg/ml (0.9%) solution for injection and merge to absolute dissolution. Infuse the entire solution to provide a 500 mg dosage of doripenem. The main difference from the first step is that there is need of withdrawing some amount of solution so that the suspension fit 250mg dosage concentration. Remove 55 ml of this solvent from the infusion container and cast off. Infuse the entire remaining solution to provide a 250 mg dose of doripenem (Grayson et al 2010). 1 g for every eight hours as a four-hour combination may be regarded in patients with boosted renal clearance, especially those with CrCl) ≥ 150 ml/min (creatinine clearance) and/or in contagions because of non-fermenting gram-negative pathogens including Acinetobacter spp. and Pseudomonas spp (Golightly 2013). This dose regimen is founded on PK/PD data. Based mostly on PK/PD deliberations, a four-hour infusion case may be more appropriate for infection with less vulnerable pathogens. This dosing regimen must also be measured in particularly grave infections (CHMP 2010). 6. The table below lists pharmacokinetic parameters for doripenem in a healthy 70 kg individual: Volume of distribution 16.8 L Total plasma clearance 15.9 L/h Plasma protein binding 8.1% Renal clearance 10.8 L/h Terminal half-life approx. 1 h The recommended dosing regimen for treatment of complicated urinary tract infection is 500 mg by IV infusion over 1 hour, every 8 hours, for 10 days. Using the data supplied, describe the disposition of doripenem over the course of the recommended regimen. The data such as total plasma clearance, renal clearance and terminal half-lie are essential consideration in the disposition of doripenem over recommended regimen. Doripenem dosing regimens for clients having CVVH (continuous venovenous hemofiltration) and CVVHDF (continuous venovenous hemodiafiltration) are designed based on an recognized efficacy principle such as free plasma doripenem solutions over the least amount inhibitory concentration such as [fT > MIC] of 1mg/L for ≥35% forming the dosing gap (Golightly 2013), while sustaining exposure underneath that with the maximum researched dose of 1000mg instilled over 1 hour for a recurring period of 8 hours in healthy subjects. This is applicable for a period of 10 to 14 days following commencement of dosing period (Brusch 2012). In patients suffering from mild renal injury such as CrCl (creatinine clearance) is > 50 to 80ml/min), no dose modification is needed. In patients diagnosed with moderate renal injury (CrCl ≥30 to 50ml/min), the dosage of doripenem must comply with 250mg for the period of every 8 hours. In patients with acute renal injury (CrCl < 30ml/min) (Brusch 2012), the dose of Doripenem need to be 250 mg for every twelve hours. In patients given a prescription of 1g every eight hours as a four-hour infusion, the dosage must be likewise adjusted. In summary moderate renal impairment (Golightly 2013): 500mg every eight hours and acute renal impairment: 500mg every twelve hours. It is apparent that the normal treatment duration of doripenem therapy varies from five to fourteen days and must be controlled and guided by the severity, location of the infection, patient’s clinical reaction and infecting pathogen. The common treatment period for patients suffering from nosocomial pneumonia, comprising ventilator-oriented pneumonia is ten to fourteen days and is frequently in the upper series for patients suffering from non-fermenting gram-negative pathogens. Doripenem has been given up to fourteen days in clinical examinations and the protection of extending durations of treatment has not been recognized. After beginning treatment with intravenous doripenem, a change to suitable oral therapy to comprehensive the treatment course is likely once clinical enhancement has been established (Golightly 2013). Dosing commendations for pathogens containing MIC >1mg/l have not been acknowledged for incessant renal substitute therapy due to the possible for gathering of doripenem-M-1 metabolite and doripenem (Brusch 2012). Close protection monitoring is recommended for patients on incessant renal replacement treatment, because of limited medical data and a predictable increased contact with doripenem-M-1 metabolite (Cunha 2012). Likewise to other β -lactam antimicrobial mechanisms, the instance that the plasma concentration of doripenem surpasses the least inhibitory concentration (%T>MIC) of the pathogens has been exposed to best associate with efficiency in pre-clinical PK/PD (pharmacokinetic/pharmacodynamic) examinations (Brusch 2012). Monte Carlo recreations using pathogen vulnerability outcomes from concluded phase III at temptations and population PK data designated that the %T>MIC intention of 35% was attained in bigger than 90% of clients with nosocomial pneumonia, complex urinary tract infections and intricate intra-internal infections, for every degrees of renal purpose (Cunha 2012). Expanding the mixture time of doripenem to four hours exploits the %T>MIC for a specified dose and is the foundation for the alternative to administer four-hour infusions in individual with nosocomial pneumonia comprising ventilator-oriented pneumonia. The above descriptions fit the data provided in the criteria and the process of poripenem disposition is appropriate for the situation (Cunha 2012). 7. Studies have reported that co-administration of doripenem with valproic acid results in a decrease in plasma concentration of valproic acid. What are the probable causes and consequences of this interaction? Doripenem is above all assisting to preserve unaffected kidneys. Mean plasma terminal exclusion half-life of doripenem in healthy youthful adults is roughly 1hour and plasma clearance is about 15.9l per hour. Medium renal clearance is approximately 10.3l/hour. The extent of this cost, joined with the considerable decrease in the removal of doripenem observed with affiliated probenecid administration, proposes that doripenem experiences tubular secretion, glomerular filtration, and re-absorption (Piscitelli, Rodvold and Pai 2011). In well youthful adults given a single 500mg dosage of Doribax, 71% and 15% of the dosage was discovered in urine as unaffected active matter and ring-opened metabolite, correspondingly. Following the provision of a distinct 500mg dosage of radiolabeled doripenem to healthy youthful adults, less than one percent of the entirety radioactivity was found in faeces. The pharmacokinetics of this dosage are linear more than a dose choice of 500mg to 2g when intravenously imparted over one hour and 500mg to 1g at what time intravenously infused more than four hours (Piscitelli, Rodvold and Pai 2011). Doripenem condensed the serum absorptions of valproic acid with AUC minimised by approximately 63%. Minimizes renal clearance of doripenem, consequence in augmented doripenem concentrations. Doripenem does not inhibit or induces main cytochrome P450 pathogens. Doripenem minimized serum valproic acid absorptions to sub-therapeutic stages in well volunteers. Consequently, serum valproic acid absorption should be checked if DORIBAX TM is prescribed concurrently with valproic acid and substitute therapies must be checked. After co-administration of valproic acid and doripenem, the serum solutions of valproic acid are minimized (AUC was decreased by 63%). This is reliable with case information for additional carbapenems, all over serum absorptions of valproic acid were minimized upon co-administration together with a carbapenem. The interaction consequence in valproic acid degrees falling under the therapeutic variety in healthy participants (Piscitelli, Rodvold and Pai 2011). Consequently, serum valproic acid solutions should be examined if DORIBAXTM is provided alongside with valproic acid and option therapies should be attempted. The PK of doripenem was unchanged by the co-administration of valproic acid (Bartlett et al 2012). Because of a drug interaction, individuals with seizure disorders inhibited with sodium valproate or valproic acid will be at an augmented risk for infiltrate seizures when therapy with Doribax® concurrently. Decrease in serum valproic acid solution to under the therapeutic solution range varying from 50 - 100 mcg/mL was assessed within 12 hours after the commencement of doripenem in fit subjects co-administered in cooperation drugs (Piscitelli, Rodvold and Pai 2011). A similar medicine interaction comprising valproic acid and other carbapenem antibacterials has been illustrated in published case documents. In some of these documentations, augmenting the dosage of sodium valproate or valproic acid did not consequence in augmented valproic acid serum absorptions. Substitute antibacterial therapies must be measured for patients getting sodium valproate or valproic acid. If provision of Doribax® is essential, supplemental anti-convulsant treatment need to be considered (Bartlett et al 2012).  8. In BNF 64, the monograph for Doribax® includes the symbol. What is this symbol? Why is this symbol in the monograph for Doribax®? Include in your answer (a) a description of what the system represents and (b) what are its implications for clinical practice in the scenario? The BNF (British National Formulary) is a pharmaceutical orientation manuscript that have a broad spectrum of data and advice on recommendations and pharmacology, together with precise facts and particulars about numerous medicines obtainable on the NHS (National Health Service), counting symptoms/indication(s), side effects, contraindications, dosages, names, legal classification and costs of obtainable proprietary and generic concentrations, and any other distinguished points (British Medical Association and Royal Pharmaceutical Society 2012). In BNF 64 the symbols are provided to indicate the status of drugs concerning registration and licensing details. The symbol ▼ is the black triangle symbol. According to ARD (Adverse Reactions to Drugs) there is guidance on prescribing; BNF 64, providing the symbols as necessary. The black triangle symbol ▼ recognizes newly licensed drugs that are checked intensively by the MHRA. This symbol in Doribax® indicated that it is a freshly licensed drug that is being monitored by the MHRA (British Medical Association and Royal Pharmaceutical Society 2012). Only restricted information is accessible from clinical examinations on the protection of new medicines. Further comprehension about the security of medicines relies on the availability of data from routine clinical examinations. ▼ Symbol in the monograph for Doribax denotes that it is a new licensed medicine. How to apply the BNF in BNF 64 denotes that clinically pertinent side-effects for largely medicines are incorporated in the monographs. Nevertheless, if a category of drugs such as sulphonylureas share the similar side-effects; these are accessible in the recommendation notes while those exclusive to a particular medicine in that category are incorporated in its entity drug monograph. The recommendation notes in the BNF may also emphasize significant safety matters and differences among drugs in their capability to grounds certain side-effects. In accordance to the side-effects under the recommendation notes for drugs hypersensitivity responses can happen, typically in the first 6–8 weeks of treatment. They consist mostly of sensitive to skin reactions which advancement seldom to erythema multiforme. The monograph for Doribax denotes the sensitive information that must be provided concerning the usage of doripenem drug (British Medical Association and Royal Pharmaceutical Society 2012). References List Acton, Q. A. (2012). Carbapenem antibiotics: Advances in Research and Application: 2011 Edition: ScholarlyPaper. ScholarlyEditions Publishers. Pg 20 -30 Bartlett, J. G., Auwaerter, P. G., & Pham, P. A. (2012). Johns Hopkins ABX guide diagnosis and treatment of infectious diseases. Burlington, MA, Jones and Bartlett Learning. http://search.ebscohost.com/login.aspx?direct=true&scope=site&db=nlebk&db=nlabk&AN=444748. Pg. 535 -539 British Medical Association, & Royal Pharmaceutical Society. (2012). British national formulary (BNF) 64. 64. London, BMJ Group. Pg. 1120 Brusch, L. J. (2012). Endocarditis Essentials. Jones & Bartlett Publishers. Pg. 125-128. CHMP (2010). Doribax (Doripenem). CHMP assessment report for paediatric use studies submitted according to Article 46 of the Regulation (EC) No 1901/2006. Pg 4-9 Cunha, B. A. (2012). Antibiotic essentials 2012. Sudbury, Mass, Physicians Press. Pg 633 -635. Elsevier Inc. (2012). Pyelonephritis. Retrieved on 31st March, 2014 from https://www.clinicalkey.com/topics/urology/pyelonephritis.html. pg 1-2 Gahart, B. L., & Nazareno, A. R. (2013). Intravenous medications: a handbook for nurses and health professionals. St. Louis, Mosby Elsevier. Pg 412 - 415 Golightly, L. K. (2013). Renal pharmacotherapy: dosage adjustment of medications eliminated by the kidneys. New York, Springer. Pg. 224 -230 Grayson, L. M, Crowe, M. S., McCarthy, S. J., Mills, J., Mouton, W. J., Norrby, R.S. Paterson, L. D. & Pfaller, A. M. (2010). Kucers The Use of Antibiotics Sixth Edition: A Clinical Review of Antibacterial, Antifungal and Antiviral Drugs Volume 1 of Kucers the Use of Antibiotics: A Clinical Review of Antibacterial, Antifungal, Antiparasitic, and Antiviral Drugs, M. Lindsay Grayson. CRC Press Publishers. Pg. 519 – 523 Jones & Bartlett Learning (2013). 2013 Nurses Drug Handbook. Burlington, MA, Jones & Bartlett Learning. Pg. 372-378 Klostranec, J. M., & Kolin, D. L. (2012). The essential med notes for medical students 2012. Whitby, Ont, McGraw-Hill. Pg. 21 Madara, B., & Pomarico-Denino, V. (2008). Pathophysiology. Sudbury, Mass, Jones and Bartlett Publishers. Pg. 513 - 516 Mayers, D. (2008). Antimicrobial drug resistance handbook. Volume 2, Volume 2. Totowa, N.J., Humana. http://dx.doi.org/10.1007/978-1-60327-595-8. Pg. 891 - 894. Nelson, K. E., & Williams, C. M. (2014). Infectious disease epidemiology: theory and practice. Burlington, Mass, Jones & Bartlett Learning. Pg. 435-457 Piscitelli, S. C., Rodvold, K., & Pai, M. P. (2011). Drug interactions in infectious diseases. New York, Humana Press. Pg. 229 -231 Schlossberg, D. (2008). Clinical Infectious Disease. Cambridge University Press Publishers. Pg. 452 - 455 Sweet, R. L., & Gibbs, R. S. (2009). Infectious diseases of the female genital tract. Philadelphia, Wolters Kluwer Health/Lippincott Williams & Wilkins. P. 261 - 265 Read More