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Regulatory authorities authorize the clinical use of generic drugs (GD) based on bioequivalence studies, which consist of the evaluation of pharmacokinetics after a single dose in vitro or in healthy individuals. There are few data on clinical equivalence between generic and branded antibiotics. Our aim was to synthesize and analyze the available evidence on the clinical efficacy and safety of generic antibiotics compared to their original formulations. A systematic review was performed on Medline (PubMed) and Embase and validated through Epistemonikos and Google Scholar. The last search was conducted on 30 June 2022. Meta-analyses of clinical cure and mortality outcomes were performed. One randomized clinical trial (RCT) and 10 non-randomized intervention studies were included. No differences in clinical cure were observed between groups in the meta-analysis (OR = 0.89, 95% CI [0.61–1.28]; I2 = 70%, p = 0.005). No difference was observed between groups when considering the use of carbapenems for overall mortality (OR = 0.99, 95% CI [0.63–1.55]; I2 = 78%) or death associated with infections (OR = 0.79, 95% CI [0.48–1.29], I2 = 67%). Most of the studies were observational, and the duration of follow-up, the characteristics of the participants, and the sites of infections were heterogeneous. Due to the uncertainty of the evidence, it is not possible to contraindicate the use of generics, which is an important strategy to expand access. [ABSTRACT FROM AUTHOR]

The antibiotic resistance arena is fraught with myths and misconceptions, leading to wrong strategies to combat it. It is crucial to identify them, discuss them in light of current evidence, and dispel those that are unequivocally wrong. This article proposes some concepts that may qualify as misconceptions around antibiotic resistance: the susceptible–resistant dichotomy; that incomplete antibiotic courses cause resistance; that resistance “emerges” in patients and hospitals; that antibiotics are mostly abused clinically; that resistance is higher in countries that use more antibiotics; that reducing antibiotic usage would reduce resistance; that financial incentives would “jumpstart” research and development of antibiotics; that generic and “original” antibiotics are the same; and that new anti-infective therapies are just around the corner. While some of these issues are still controversial, it is important to recognize their controversial status, instead of repeating them in specialized literature and lectures and, especially, in the planning of strategies to cope with resistance. [ABSTRACT FROM AUTHOR]

Regulatory authorities authorize the clinical use of generic drugs (GD) based on bioequivalence studies, which consist of the evaluation of pharmacokinetics after a single dose in vitro or in healthy individuals. There are few data on clinical equivalence between generic and branded antibiotics. Our aim was to synthesize and analyze the available evidence on the clinical efficacy and safety of generic antibiotics compared to their original formulations. A systematic review was performed on Medline (PubMed) and Embase and validated through Epistemonikos and Google Scholar. The last search was conducted on 30 June 2022. Meta-analyses of clinical cure and mortality outcomes were performed. One randomized clinical trial (RCT) and 10 non-randomized intervention studies were included. No differences in clinical cure were observed between groups in the meta-analysis (OR = 0.89, 95% CI [0.61–1.28]; I2 = 70%, p = 0.005). No difference was observed between groups when considering the use of carbapenems for overall mortality (OR = 0.99, 95% CI [0.63–1.55]; I2 = 78%) or death associated with infections (OR = 0.79, 95% CI [0.48–1.29], I2 = 67%). Most of the studies were observational, and the duration of follow-up, the characteristics of the participants, and the sites of infections were heterogeneous. Due to the uncertainty of the evidence, it is not possible to contraindicate the use of generics, which is an important strategy to expand access.

Background: About 60%–90% of healthcare spending in India is on medicine which is mainly out of pocket. Almost all the drugs including antibiotics are available as brands with variable cost. Indian government formulated National List of Essential Medicines (NLEM) to ensure availability of affordable medicines to the population. Prescribing drugs from NLEM and considering the cost of drug, especially antibiotics in practice, can reduce cost of treatment and patient's out-of-pocket expenditure. Objective: The objective of the study is to analyze cost variation of different antibiotic brands available in Indian market with reference to NLEM. Materials and Methods: List of antibiotics listed in the NLEM 2015, India, was prepared. Percentage cost variation and cost ratio of different brands of these antibiotics were calculated and compared. Results: We found 17 antibiotics listed in NLEM 2015. The number of brands varied from 2 to 102. We found wide cost variations among different brands of same antibiotics. Minimum cost variation was 7.34% (for ciprofloxacin 200 mg/100 ml vial) while maximum 1049.82% (for azithromycin 500 mg tablet). Conclusion: There is wide cost variation in different brands of same antibiotics listed in the NLEM. Prescribers should prescribe cheaper brands of antibiotics to ensure that patients complete the course of treatment and thus reduce development of resistance to antibiotics.

Background: About 60%-90% of healthcare spending in India is on medicine which is mainly out of pocket. Almost all the drugs including antibiotics are available as brands with variable cost. Indian government formulated National List of Essential Medicines (NLEM) to ensure availability of affordable medicines to the population. Prescribing drugs from NLEM and considering the cost of drug, especially antibiotics in practice, can reduce cost of treatment and patient's out-of-pocket expenditure. Objective: The objective of the study is to analyze cost variation of different antibiotic brands available in Indian market with reference to NLEM. Materials and Methods: List of antibiotics listed in the NLEM 2015, India, was prepared. Percentage cost variation and cost ratio of different brands of these antibiotics were calculated and compared. Results: We found 17 antibiotics listed in NLEM 2015. The number of brands varied from 2 to 102. We found wide cost variations among different brands of same antibiotics. Minimum cost variation was 7.34% (for ciprofloxacin 200 mg/100 ml vial) while maximum 1049.82% (for azithromycin 500 mg tablet). Conclusion: There is wide cost variation in different brands of same antibiotics listed in the NLEM. Prescribers should prescribe cheaper brands of antibiotics to ensure that patients complete the course of treatment and thus reduce development of resistance to antibiotics. [ABSTRACT FROM AUTHOR]

Background: The impact of antimicrobials generic entry (GE) is controversial. Their introduction could provide an economic benefit yet may also increase their consumption, leading to a higher risk of resistance. Our aim was to analyze the impact of GE on trends of antimicrobial consumption in an acute-care hospital. Methods: A retrospective quasi-experimental interrupted time series analysis was conducted at a 400-bed tertiary hospital in Barcelona, Spain. All antimicrobials for systemic use for which a generic product entered the hospital from January 2000 to December 2019 were included. Antimicrobial consumption was expressed as DDD/100 bed days. Results: After GE, the consumption of cefotaxime (0.09, p < 0.001), meropenem (0.54, p < 0.001), and piperacillin-tazobactam (0.13, p < 0.001) increased, whereas the use of clindamycin (−0.03, p < 0.001) and itraconazole (−0.02, p = 0.01) was reduced. An alarming rise in cefepime (0.004), daptomycin (1.02), and cloxacillin (0.05) prescriptions was observed, despite not achieving statistical significance. On the contrary, the use of amoxicillin (−0.07), ampicillin (−0.02), cefixime (−0.06), fluconazole (−0.13), imipenem–cilastatin (−0.50) and levofloxacin (−0.35) decreased. These effects were noticed beyond the first year post GE. Conclusions: GE led to an increase in the consumption of broad-spectrum molecules. The potential economic benefit of generic antibiotics could be diluted by an increase in resistance. Antimicrobial stewardship should continue to monitor these molecules despite GE.

Septic arthritis is classified among the acute emergencies of joint diseases. Gram-positive cocci are responsible in 75-80% of the cases, while Gramnegative bacilli may be the etiological agents in case of compromised immunity, intravenous drug abuse, advanced age, or iatrogenic infections. Cases of posttraumatic septic arthritis due to Gram-negative bacilli in immunocompetent patients are reported in the literature. In this paper we present a severe septic arthritis due to Serratia marcescens in a 43-year-old man with multiple trauma, right patellar and femoral condyle fracture after a traffic accident, three days after an irrigation and debridement procedure was performed. The surgical procedure had to be repeated four times while he was receiving medical treatment. A literature search in PubMed using the keywords "Serratia marcescens and septic arthritis" on October 10th 2017, we found 37 articles, of which 18 were case reports or case series. Of those 18 articles, seven cases were hospital-acquired, five were in intravenous drug users, two were trauma related, one was concomitant with rheumatoid arthritis, one was in a neonate, one was due to intra-articular injection, and one article described an epidemic due to usage of contaminated benzalkonium chloride solution as an antiseptic. We also found a case by searching Turkish Medline reported in a ten-week-old baby with Escobar syndrome. In our case, although hospital-acquired infection cannot be ruled out, we believe that this was a community-acquired infection due to contamination of the open dirty wound, as the irrigation procedure was done in sterile operating room conditions and no other such case has ever been identified. As prompt diagnosis and treatment is critical in prognosis of septic arthritis, we emphasize the possible role of Gram-negative bacilli in posttraumatic cases.

Recent studies have shown that the pharmacodynamic (PD) index driving the efficacy of β-lactam/β-lactamase inhibitor combinations such as ceftazidime/avibactam and ceftolozane/tazobactam is the percentage of time the free inhibitor concentration is above a threshold ( f T >threshold ). However, data with piperacillin/tazobactam (TZP) are scarce. Here we aimed to assess the relationship between f T >threshold and TZP antibacterial efficacy by a population pharmacokinetic study in mice and dose–effect experiments in a neutropenic murine thigh infection model with two isogenic strains of Escherichia coli differentially expressing TEM-1 β-lactamase. We also explored the dynamics of resistance selection with the innovator and a non-equivalent generic, extrapolated the results to the clinic by Monte Carlo simulation of standard TZP doses, and estimated the economic impact of generic-selected resistance. The f T >threshold index described well the efficacy of TZP versus E. coli , with threshold values from 0.5 mg/L to 2 mg/L and mean exposures of 42% for stasis and 56% for 1 log 10 kill. The non-equivalent generic required a longer exposure ( f T >threshold 33%) to suppress resistance compared with the innovator ( f T >threshold 22%), leading to a higher frequency of resistance selection in the clinical simulation (16% of patients with the generic vs. 1% with the innovator). Finally, we estimated that use of TZP generics in a scenario of 25% therapeutic non-equivalence would result in extra expenses approaching US$1 billion per year in the USA owing to selection of resistant micro-organisms, greatly offsetting the savings gained from generic substitution and further emphasising the need for demonstrated and not assumed therapeutic equivalence. [ABSTRACT FROM AUTHOR]

Septic arthritis is classified among the acute emergencies of joint diseases. Gram-positive cocci are responsible in 75-80% of the cases, while Gramnegative bacilli may be the etiological agents in case of compromised immunity, intravenous drug abuse, advanced age, or iatrogenic infections. Cases of posttraumatic septic arthritis due to Gram-negative bacilli in immunocompetent patients are reported in the literature. In this paper we present a severe septic arthritis due to Serratia marcescens in a 43-year-old man with multiple trauma, right patellar and femoral condyle fracture after a traffic accident, three days after an irrigation and debridement procedure was performed. The surgical procedure had to be repeated four times while he was receiving medical treatment. A literature search in PubMed using the keywords "Serratia marcescens and septic arthritis" on October 10th 2017, we found 37 articles, of which 18 were case reports or case series. Of those 18 articles, seven cases were hospital-acquired, five were in intravenous drug users, two were trauma related, one was concomitant with rheumatoid arthritis, one was in a neonate, one was due to intra-articular injection, and one article described an epidemic due to usage of contaminated benzalkonium chloride solution as an antiseptic. We also found a case by searching Turkish Medline reported in a ten-week-old baby with Escobar syndrome. In our case, although hospital-acquired infection cannot be ruled out, we believe that this was a community-acquired infection due to contamination of the open dirty wound, as the irrigation procedure was done in sterile operating room conditions and no other such case has ever been identified. As prompt diagnosis and treatment is critical in prognosis of septic arthritis, we emphasize the possible role of Gram-negative bacilli in posttraumatic cases. [ABSTRACT FROM AUTHOR]

Generic drugs have been used extensively in many developed countries, although their use in Japan has been limited. Generic drugs reduce drug expenses and thereby national medical expenditure. Because generic drugs provide advantages for both public administration and consumers, it is expected that they will be more widely used in the future. However, the diffusion rate of generic drugs in Japan is quite low compared with that of other developed countries. An investigation on generic drugs conducted by the Ministry of Health, Labour and Welfare in Japan revealed that 17.2 % of doctors and 37.2 % of patients had not used generic drugs. The major reasons for this low use rate included distrust of off-patent products and lower drug price margin compared with the brand name drug. The generic drugs available in the market include external drugs such as wet packs, antihypertensive agents, analgesics, anticancer drugs, and antibiotics. Among them, antibiotics are frequently used in cases of acute infectious diseases. When the treatment of these infections is delayed, the infection might be aggravated rapidly. The pharmacokinetics-pharmacodynamics (PK-PD) theory has been adopted in recent chemotherapy, and in many cases, the most appropriate dosage and administration of antibiotics are determined for individual patients considering renal function; high-dosage antibiotics are used preferably for a short duration. Therefore, a highly detailed antimicrobial agent is necessary. However, some of the generic antibiotics have less antibacterial potency or solubility than the brand name products. We showed that the potency of the generic products of vancomycin and teicoplanin is lower than that of the branded drugs by 14.6 % and 17.3 %, respectively. Furthermore, we confirmed that a generic meropenem drug for injection required about 82 s to solubilize in saline, whereas the brand product required only about 21 s. It was thought that the cause may be the difference in size of bulk particle and amount of solubilizer. The Japanese government hopes to increase the diffusion rate of generic drugs (in terms of quantity) from 20.2 % in 2010 to 30 % or more in 2012, and therefore it will be necessary to clarify the advantages of generic antibiotics in terms of expenditure and equivalency with the branded drugs. [ABSTRACT FROM AUTHOR]

Background: The impact of antimicrobials generic entry (GE) is controversial. Their introduction could provide an economic benefit yet may also increase their consumption, leading to a higher risk of resistance. Our aim was to analyze the impact of GE on trends of antimicrobial consumption in an acute-care hospital. Methods: A retrospective quasi-experimental interrupted time series analysis was conducted at a 400-bed tertiary hospital in Barcelona, Spain. All antimicrobials for systemic use for which a generic product entered the hospital from January 2000 to December 2019 were included. Antimicrobial consumption was expressed as DDD/100 bed days. Results: After GE, the consumption of cefotaxime (0.09, p < 0.001), meropenem (0.54, p < 0.001), and piperacillin-tazobactam (0.13, p < 0.001) increased, whereas the use of clindamycin (−0.03, p < 0.001) and itraconazole (−0.02, p = 0.01) was reduced. An alarming rise in cefepime (0.004), daptomycin (1.02), and cloxacillin (0.05) prescriptions was observed, despite not achieving statistical significance. On the contrary, the use of amoxicillin (−0.07), ampicillin (−0.02), cefixime (−0.06), fluconazole (−0.13), imipenem–cilastatin (−0.50) and levofloxacin (−0.35) decreased. These effects were noticed beyond the first year post GE. Conclusions: GE led to an increase in the consumption of broad-spectrum molecules. The potential economic benefit of generic antibiotics could be diluted by an increase in resistance. Antimicrobial stewardship should continue to monitor these molecules despite GE. [ABSTRACT FROM AUTHOR]