Keywords

2.1 Introduction

Antimicrobials are considered as most effective drug for the treatment of various infections in humans. In the history of medicine, penicillin was marked as the beginners of the “golden era” of antibiotics. Various antibiotics from different families were produced during 1940–1962 for the treatment of various infections caused by variety of bacteria. In the past two to three decades several new antibiotics were also developed through structural modifications of previous antibiotics to make them remain effective. These antibiotics were extensively employed in human healthcare due to their essential requirement for bacterial infection treatment, surgical involvements, and prophylactic cure and in cancer. This has resulted in the increase in global use of antibiotics due to which the usage were at the peak between 2000 and 2010 worth $40 billion per year (O’Neill 2015) with expected 36% increase in the future, which demonstrate their importance from societal and economic perspective (Van Boeckel et al. 2014). Today, antibiotics have the wide range of usage in hospitals (Cabello 2006; Sarmah et al. 2006) for the cure of various diseases in hospitals but massive development and flourishing inappropriate usage (Van Boeckel et al. 2014, 2015) have resulted in many challenges. Beside of antibiotics significance in treatment of diseases in hospitals, they are of concern due to their potential genotoxic effects. Further, the detection of large number of antimicrobials in the environment poses some serious threats including alteration in aquatic ecosystem, spread of antimicrobial resistance, and threats to public health (Daughton and Ternes 1999; Boxall 2004; Runnalls et al. 2010; Brandt et al. 2015).

2.2 Antibiotics and Their Use in Hospitals: An Overview

Antibiotics are designed to have such molecular structures and functions which make them to show activity against variety of bacteria which are responsible for causing many infections related to gastrointestinal tract, respiratory tract, skin infections, and many sexually transmitted diseases. Globally about 30% increase in antibiotic consumption was observed during 2000 and 2010 reaching 50–70 billion standard units, out of which about 20% was applied in the hospitals for the treatment of infections (Van Boeckel et al. 2014). Only in the USA 23 × 106 kg of antibiotics are presently in use on annual basis, out of which half of antibiotics are used for general public in hospitals and communities (Lederberg and Harrison 1998). The use of antibiotics mainly depend upon the economic status of the country and the population they hold. In 2000 the antibiotic consumption pattern was high in the USA, France, and Italy while it was reported to be low in many low- or medium-income countries. However a dramatic increase in antibiotic consumption was observed in many developing countries particularly in China, India, and Pakistan (Klein et al. 2018). This global increase in the use of antibiotics are putting burden of many untreated bacterial infections in humans, so it is the need of time not only to quantify the antibiotic use but also to focus on the reduction of antibiotic consumption in developed and developing nations. The antibiotic consumption pattern in hospitals of different countries over the period of time have been presented in Table 2.1.

Table 2.1 Antibiotics consumption in hospitals of various countries over the period of time
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2.2.1 Classification of Antibiotics

Based on the structures and functions antibiotics have been classified into broad range of groups. Within same group the antibiotics are active against the related bacteria due to similar pharmacologic and chemical properties. Several classifications of antibiotics have been developed depending upon their action of mechanism or infection cured. The most important groups of antibiotics include aminoglycosides, β-lactams (penicillin, cephalosporins, carbapenems), cephalosporins, chloramphenicol, imidazoles, lincosamides, macrolides, quinolones, rifamycins, tetracyclines, and others (Pinheiro et al. 2019). Various groups of antibiotics and examples are presented in Fig. 2.1 and explained in following sections.

Fig. 2.1
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Classification of antibiotics

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2.2.1.1 Aminoglycosides

Aminoglycosides were mostly effective against Gram-negative bacteria with limited potential to work against Gram-positive bacteria. Their history linked with the discovery of streptomycin back into 1943. Aminoglycosides kill bacteria through inhibition of protein synthesis and mostly they were applied through veins instead of oral administration due to poor absorption during digestion. Streptomycin from this group was very effective against tuberculosis orcysticfibrosis. Moreover, these are commonly used prophylactically in premature infants (Hayward et al. 2019). However due to toxicity of this drug its use has also been limited today. Aminoglycosides are divided into two main groups:

  1. 1.

    Mycin (Kanamycin, Neomycins)

  2. 2.

    Micin (Amikacin, Gentamicin)

Aminoglycosides are derived by various species of Micromonospora and Streptomyces bacteria. Aminoglycosides produced by Streptomyces species are referred with suffix “mycin” whereas those produced from Micromonospora are referred the suffix “micin” (Farouk et al. 2015).

2.2.1.2 β-Lactams

The discovery of penicillin in 1928 led to the development of β-lactam antibiotics which consist of β-lactam ring, penicillin (amoxicillin), and cephalosporin. The β-lactams were extensively used class of antibiotics which showed activity against Gram-positive bacteria by interfering the synthesis of peptidoglycan in bacterial cell wall. In human β-lactams chemicals are most successful ever used antibiotic to cure infections due to its wide spectrum properties such as oral availability, activity, lack of toxicity, pharmacokinetics, and bactericidal action (Foster 2019). β-Lactams are further divided into two groups, which include:

  1. (a)

    Cephalosporins

  2. (b)

    Penicillin (methicillin, isoxazoyl penicillins, amoxicillin)

  3. (c)

    Carbapenems

  4. (d)

    Monobactams

Among various classes, semi-synthetic cephalosporins belong to β-lactams antibiotics which have wide applications for the treatment of human-related diseases and considered as second- or third-line therapy. According to World Health Organization (World Health Organization, 2017) cephalosporins have been declared as the most critical and highly prioritized medicine for human therapy and mainly used to combat gonorrhea infections and meningitis (BPAC 2011).

In general category, penicillin antibiotics is another β-lactam drug which have been extensively applied for curing and preventing infectious diseases. The aforementioned antibiotic is used in a drastic means for combating infections due to bacteria for many years, where its significant role in human medicine is quite popular. Penicillin are basically bicyclic organic molecules which are formed by the fusion of a β-lactam ring and a five-membered thiazolidine ring, combined at various side chains. Penicillins can be classified further into six subclasses, depending upon use, chemical structure, spectrum (extended, broad, and narrow), susceptibility to β-lactamase destruction, and source (natural, synthetic, semisynthetic). Benzyl penicillin or penicillin-G belongs to the first subclass whereas oxacillin, cloxacillin, and dicloxacillin belong to the third class (Alampanos et al. 2019).

Cephalosporin antibiotic drugs belong to the “new non-β-lactam” antibiotics which has capability to disinfect activity of Klebsiella pneumonia. Some novel cephalosporins including ceftolozane are applied in combination with tazobactam for the cure and treatment of aeruginosa infections (Peri et al. 2019).

2.2.1.3 Chloramphenicol

Chloramphenicol, also known as CAP, is a broad spectrum antibiotic group that is used for curing activity of both Gram-positive and Gram-negative bacteria (Yanovych et al. 2018). Chloramphenicol is applied to counter a broad variety of infections, which includes common cold, typhoid fever, meningitis, and bronchitis (Sharma et al. 2019). Due its side effects, this antibiotic is prohibited in many cases because of its cause of serious illnesses such as blood dyscrasias, suppression of bone marrow, gray baby syndrome, and minor effects such as headache and nausea.

2.2.1.4 Macrolides

Macrolides are a group of antibiotics medically in use for more than six decades and have the capability to inhibit a broad range of bacteria frequently used in feedlots and hospitals (Liu et al. 2014). Macrolides mainly worked against Gram-positive bacteria just like β-lactam through growth and reproduction prevention of bacteria by hindering synthesis of protein. They inhibit microbial cell growth by interfering the function of ribosome (Vázquez-Laslop and Mankin 2018). Erythromycin from this class is the most frequently used antibiotics; though bacteria has developed resistance to this group but still it is the second most prescribed group of antibiotics. Macrolide is typically a natural chemical with variety of biological activities including antiparasitic, antimalarial, and antifungal activities. A small class of natural macrolides is 12-membered macrolides, for example, pandangolide 1–4, cladospolide A and B, ozoroalide, aspergillolide, chloriolide, and balticolid (Huang et al. 2019). Macrolide chemicals have an overlapping binding site on ribosome of bacteria structurally distinct, streptogramins and lincosamides, resulting to clusters of genes encoding resistance to macrolides, called Macrolide-Lincosamide-Streptogramin resistance genes (Sutcliffe and Leclercq 2002).

2.2.1.5 Quinolones

The quinolones is an important class of synthetic antibiotics which have broad-spectrum activity against both Gram-positive and Gram-negative bacteria. Quinolones act in bactericidal manner through interference with the replication and transcription of DNA in bacteria cells. They are used in treatment of humans and food-producing animals (Zhang et al. 2017). Quinolones were mainly used to cure urinary tract infections and those which cannot be treated with other antibiotics. Besides their broad spectrum of antibacterial activity, quinolone exhibited high pharmacological properties such as antitumor, antituberculosis, antifungal, anti-HIV, antimalarial, and antiplasmodial activities. Quinolones including fluoroquinolones have efficient in vitro antiplasmodial activity against hepatic and erythrocytic stages of CQ-sensitive and CQ-resistant P. falciparum. Moreover, fluoroquinolones also exhibited excellent in vivo potency, which make them efficient candidates for the chemoprophylaxis (Fan et al. 2018). Up till now four generations/classes of quinolone antibiotics have been formulated (Hernandez-Montelongo et al. 2014) which contains various types of quinolones.

  1. 1.

    First-generation quinolones (norfloxacin, cinoxacin)

  2. 2.

    Second-generation quinolones (norfloxacin, ciprofloxacin, ofloxacin, enrofloxacin, and lomefloxacin)

  3. 3.

    Third-generation quinolones (sparfloxacin, levofloxacin, moxifloxacin)

  4. 4.

    Fourth-generation quinolones (trovafloxacin)

Currently, the most common quinolones in markets are second-generation quinolone antibiotics which include norfloxacin, ciprofloxacin, ofloxacin, enrofloxacin, gemifloxacin, lomefloxacin etc. (Gidwani and Vyas 2014) that are used in various bacterial infections. Among them, ciprofloxacin has potential to cause toxicity to central nervous, liver, and kidney toxicity and hematological toxicity in the human body. In case of third- and fourth-generation quinolone, their use is very limited because of their serious side effects. Moreover, the newly developed generation of quinolones has more genotoxic potential for instance; fourth-generation quinolones are two orders of magnitude high genotoxic as compared to third-generation quinolones (Cao et al. 2019).

2.2.1.6 Rifamycin

The rifamycin antibiotics are most commonly used in hospitals and clinics for the treatment of nontuberculous mycobacterial diseases, prophylaxis, and tuberculosis (active and latent infection) infections. Rifamycin antibiotic are complex macrocyclic molecules attained from an Actinomycete bacterium which play a preponderant role in therapeutics as antibiotics. Rifamycin combine with the RNA polymerase β-subunit which inhibit the RNA transcription, and therefore the bacterial synthesis. The side effects of the rifamycin antibiotics are associated with the discoloration of the skin and body fluids. The main class of rifamycin includes:

  1. 1.

    Rifampin

  2. 2.

    Rifabutin

  3. 3.

    Rifapentine

Among semisynthetic antibiotics, two of their most applied and established rifamycin are rifampicin and rifaximi. Rifampicin is used for curing tuberculosis and inhibition of cancer cells growth in human, whereas rifaximi is applied to treat Crohn’s, diarrhea, and diverticular and intestinal infections (Jimenez-Lopez et al. 2016).

2.2.1.7 Sulfonamides

Sulfonamide is broad spectrum group of antibiotics which have a range of activities against various infections caused by Gram-positive and Gram-negative bacteria. A substantial number of this group of antibiotics was discovered based on the Prontosil which was the first sulfonamide antibiotic discovered in 1932 and made commercially available. Sulfonamide antibiotics do not kill bacteria, instead they inhibit synthesis of B vitamin folate required for nucleic acid formation, and this inhibition of folic acid results in the growth and reproduction inhibition of bacteria. The main sulfonamide type RSO2NH2 compounds have various types of pharmacological factors which includes antiviral, anticancer, and antibacterial activities; and protease inhibition, carbonic anhydrase inhibition, cyclooxygenase 2 inhibition, and diuretic action (Demir and Köksal 2019). The sulfonamides helps to treat dysentery, meningococcal meningitis, septicemia, tonsillitis, and urinary tract infections caused by Chlamydia trachomatis, E. coli, Enterobacter, Salmonella, and Shigella. The most common antibiotics in sulfonamides group are sulfamethoxazole/trimethoprim, azulfidine, and zonisamide. Their use has been limited these days due to resistance developed by bacteria against these antibiotics and their hepatotoxicity effects. New efforts have been made to develop such sulfonamide group which are potent inhibitors of the Alzheimer’s disease associated butyrylcholinestarase (Apaydin and Török 2019).

2.2.1.8 Tetracyclines

Tetracyclines are one of another broadly used antibiotic class especially in the USA and Europe, applied to cure bacterial infections of respiratory and urinary tract. Tetracyclines act in a similar way like sulfonamides and prevent synthesis of protein, followed by growth and reproduction inhibition. Tetracyclines appeared among the most prescribed antibiotics medicine for human application (Van Boeckel et al. 2014). Aminoglycosides play a key role for curing and treatment of Methicillin-resistant Staphylococcus aureus (MRSA) infections. MRSA has long been familiar as one of the main devious pathogens which is involved in nosocomial infections. It has been reported that aminoglycosides are mainly bactericidal and commonly applied synergistically in amalgamation with either glycopeptide or beta-lactam antibiotics (Goudarzi et al. 2019).

2.2.1.9 Triazole

Triazole is also known as 1,2,4-triazole and is a common pharmacophore in many drugs (Bonandi et al. 2017) which possess anti-bacterial, antifungal, antitubercular, and antitumor activities. This is the reason that triazole have wide application in clinics and hospitals to treat variety of infections and diseases (Zhang et al. 2019). Furthermore, 1, 2, 4-triazole derivatives also play an important role in the development of novel medicines by hybrid molecules. Hybrid molecules are those chemical entities which have two or more structures having different biological functions. Therefore, hybrid molecules of 1, 2, 4-triazole are marked with the dual activities, for instance the new drug may provide excellent potency against both drug-resistant bacteria and drug-sensitive (Zhang et al. 2019). The activity of various antibiotics against different infections is summarized in Table 2.2.

Table 2.2 Antibiotics and their activity against variety of infections
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2.3 Misuse of Antibiotics in Hospitals

Antibiotics are critical element of today’s medicine in hospitals but they are on the top of the list of misused medicines in hospitals. Mostly antibiotics are used for the nosocomial infections and the great occurrence of infectious diseases results in the extensive practice of antibiotics in hospitals that may or may not be in an appropriate way (Wolff 1993). Due to lack of proper hygiene, misuse of antibiotics and encoded genetic elements antimicrobial resistance is becoming a great issue in the hospitals. The four major elements that are responsible for the antibiotic misuse and resistance problems in hospitals are: (1) infection, (2) patient, (3) pharmacist, and (4) physician. The role of physicians in inappropriate prescription cannot be ignored as they focus more on short-time treatment with frequent results. While the private pharmacist contribute in this problem by supplying antibiotics without verifying the physician’s prescription (Weinstein 2001). The absurd taking of antibiotics affects the whole body in different ways like allergic reactions, antibiotic resistance, antibiotic-resistant gonorrhea, and toxicity (Li 2014).

In the USA about 30% of the drug budgets in hospital is allocated for antibiotics which is correlated with the inappropriate use of antibiotics usage for more than three decades even after strict control measures. Furthermore, it was reported in 2003 that out of seven billion $ spent on antibiotics usage on annual basis, about four billion $ have been spent on the treatment of infections caused by hospital-acquired infections (Guven and Uzun 2003). Wrong prescription in hospitals increases the exposure of patients and complications (Fridkin et al. 2014), so there is a need of improved prescription of antibiotics in hospitals to offer more benefit to patients than complications. Patient outcomes can be improved by using antibiotics in an appropriate way in hospitals aiming to:

  1. 1.

    Cure infections with an agent that requires a short time with minimum aftereffects.

  2. 2.

    Control the spread and development of resistant microbial agents.

  3. 3.

    Ensure better healthcare facilities on fair treatment charges.

To control the misuse of antibiotics many hospitals limit the recommendation of antibiotics by prescribing only one to two antibiotic drugs from each class. The effectiveness and appropriateness of antibiotics may be improved by the use of order forms and review of antibiotic treatment on next day of prescription (Davey et al. 2013). The computerized order form is the most effective intervention to ensure correct prescription of antibiotics. To prevent the misuse of antibiotics and enhancement of treatment it is the responsibility of doctors to correctly prescribe antibiotics to patients for good quality treatment at all stages.

2.4 Types of Wastes Generated in Hospitals

Hospital waste is categorized as medical and nonmedical waste. The medical waste is produced from various activities including first aid, emergency, operations, laboratories, and diagnosis, whereas the nonmedical waste includes the waste generated from kitchens, toilets, laundry, etc. There is high variability in the production of hospital waste depending upon hospital size, wards, services offered, country, season, etc. (Verlicchi et al. 2012; Al Aukidy et al. 2014). It was estimated that about 4 kg of the waste produced in hospitals contains at least 1 kg of the infectious waste (Babatola 2008), similarly 10–25% of the residual waste is proven to be toxic which intensify and promote disease transmission among humans (Tsakona et al. 2007).

In past gradual increase in the use of antibiotics was observed which has reached between 100,000 and 200,000 tons per year (Wise 2002) making antibiotics as potential contaminants due to their long-term and synergistic effects at low concentrations when they enter in the environment (Lombardo-Agüí et al. 2014; Oliveira et al. 2015). These antibiotics may associate with one another and can present genuine difficulties to human medicinal services. There are mainly two types of wastes generated in hospital, i.e., chemical waste and biological waste. This waste when enters into the environment from hospitals results in decreasing the efficiency of medicine and promoting bacterial resistance which has threatened the public and ecosystem health. The pathway of antibiotics released in hospitals have been presented in Fig. 2.2.

Fig. 2.2
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Pathway of antibiotics from hospital waste into the environment

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2.4.1 Chemical Waste

The most commonly detected chemical in the hospital waste are antibiotics due to their excessive use and consumption for the treatment of various types of infections. Sometimes antibiotics are ineffectively used and discharged as the active parent substance in the hospital waste. It was reported that antibiotics when given to patients they excreted 50–80% in the urine and 4–30% in the feces as parent compound (Alcock et al. 1999; Jjemba 2006; Verlicchi et al. 2012; Al Aukidy et al. 2014). On the other hand, the metabolites produced due to consumption of antibiotics remain bioactive and sometime result in the transformation to parent compound. This was observed in case of sulfonamides when N4-acetylsulfapyridine and N4-acetylsulfamethazine has changed to the parent compound (Bonvin et al. 2012). Further these antibiotics possess high stability and low volatilization which result in the persistence of these contaminants in the hospital waste.

Hospital effluents are one of the principle sources of contamination to the natural environment. After management in the hospital and excretion from patients, these antibiotic substances are released into hospital effluents. On the other hand, sometimes unused drugs are also disposed of down drains. In hospitals various antibiotics from different groups are used with high concentrations which is an indicator that major contributor of antibiotics pollution are hospitals. Many studies reported the prevalence of antibiotics in hospital waste water (Giuliani et al. 1996; Guardabassi et al. 1998; Alder et al. 2003) due to their incomplete removal in treatment plants where the antibiotics get readily adsorbed to sludge with limited biodegradation which make them to persist in the waste water and enter into surface water through effluents (Verlicchi et al. 2010). The removal efficiency of different methods used for antibiotic residues treatment in hospital waste has been presented in Table 2.3. Fluoroquinolone group of antibiotics are considered as genotoxic and these antibiotics were widely detected in hospital effluents due to limited removal with the concentrations ranging between 3000 and 87,000 ng L−1 and playing major role in the growth of antibiotic-resistant bacteria (Hartmann et al. 1998). Among various classes of antibiotics, sulfonamides and fluoroquinolones persist for longer period whereas macrolides and tetracyclines persist for comparatively longer time in the absence of sunlight. On the other hand, the other two groups of antibiotics including aminoglycosides and β-lactam showed the least persistence in the environment (Huang et al. 2011). β-Lactams and fluoroquinolones were widely used in inpatients but β-lactams seldom detected in the waste water due to its rapid cleavage on hydrolysis compared to fluoroquinolones (Bréchet et al. 2014) which is persistent and resulted in the detection with high concentrations in hospital waste water (Rodriguez-Mozaz et al. 2015). The concentration of antibiotics from various groups in hospital wastewater from different countries have been presented in Table 2.4. Throughout the most recent decades, an expanding assemblage of evidence has demonstrated that antitoxins entering the environment in this manner pose potential consequences for nontarget life forms and public health (Boxall 2004; Runnalls et al. 2010; Brandt et al. 2015).

Table 2.3 Removal efficiency of various methods used for the treatment of hospital waste water
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Table 2.4 Concentration of antibiotics from various groups in hospital wastewater from different countries
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2.4.2 Biological Waste

Antibiotics use in hospitals resulted in the prevalence of their residues in hospital waste which has emerged as global concern. This happened due to the lack of primary treatment of hospital waste water or the behavior of antibiotics in treatment plants. The antibiotic residues in hospital waste water continuously exert a strong selective pressure on ARBs and create favorable conditions (nutrient, pH, temperature, antibiotics) for antibiotic-resistant bacteria to promote gene transfer among other bacteria (Varela et al. 2014). This relationship between antibiotics, antibiotic-resistant bacteria, and rearrangement of bacterial communities has been presented in the past (Gros et al. 2013; Stalder et al. 2013; Bréchet et al. 2014; Varela et al. 2014; Baricz et al. 2018). Hospital waste holds variety of bacteria released from patient body and hospital equipment which includes many pathogens. The most common pathogens Escherichia coli and Pseudomonas aeruginosa responsible for causing urinary and respiratory tract infections has been reported by Tuméo et al. (2008). Further great number of vancomycin-resistant enterococci (VRE), multidrug-resistant, Pseudomonas aeruginosa, Enterococcus faecalis, and Enterococcus faecium were also reported in hospital effluents. It was reported that about 15% of infections in hospitals are only caused by Pseudomonas aeruginosa (Hocquet et al. 2016). So the hospital effluents containing these types of pathogens and antibiotic-resistant bacteria make these organisms to play a significant role in the evolution and propagation of these organisms and the related genes. These evidences raised an emerging concern not only to the human health but also to the environment (Jernberg et al. 2010).

The hospital effluents contain this type of biological waste and antimicrobial residues have induced the great level of concern today than ever in the history. This is evident from the report stated that infections may enhanced up to 120,000 during surgery due to decrease in the efficiency of antibiotics which have caused 6300 deaths in the USA (Teillant et al. 2015). If the spread of antimicrobial resistance will continue with the evolution of pathogens, this death rate may even rise to great numbers. Recently it has been reported that a bacterial strain isolated from livestock and patient in China is multidrug resistant and can resist to colistin (Liu et al. 2016) which is considered as “last-line” medicine for such type of pathogens (Biswas et al. 2012). These evidences suggest to step up in the hospital waste management for the protection of human and ecosystem health. The problem of hospital waste management is global but it is not properly managed in the developing countries which can result in greater effects in these countries (Tudor et al. 2005).

2.5 Environmental Burden of Hospital Waste

2.5.1 Antibiotics

The antibiotics used in hospitals ends up in the environment due to limited metabolization in human body and incomplete removal in the treatment plants. Another way of these antibiotics in the environment is through the disposal of the waste through landfills (Wang et al. 2015). This heap of antibiotic agents scattered in nature could have critical ramifications for environments and human well-being, perhaps increasing sensitivities in people and propagation of antibiotic resistance. Antimicrobials are usually detected at subtherapeutic concentrations in the environment (Kümmerer 2003) but continual exposure to these drugs increased their resistance in the environment (Kümmerer 2004). Bacterial protection from antimicrobial agents has been accounted for various environment including surface water (Ash et al. 2002), sewage (Iversen et al. 2002), drinking water (Schwartz et al. 2003), soil (Burgos et al. 2005), and marine ecosystem (Kim et al. 2004). There has been a serious threat about the presence of antimicrobial in the environment that the U.K House of Lords expressed it as: “Resistance to antibiotics constitutes a major threat to public health and ought to be recognised as such more widely than it is at present” (Wise et al. 1998). The focus should be given on the appropriate use of antimicrobials, installment of primary treatment system, followed by the improvement in the treatment processes in the hospitals. Because if they will not be appropriately prescribed by the medical practitioners and eliminated in the treatment plants, they will enter in the environment and pose threat to public and ecosystem health.

2.5.2 Development of Antibiotic Resistance in Environment

Antibiotic resistance can be developed through selective pressure caused by antimicrobials or naturally by spontaneous alteration in genes due to the lack of selective pressure in the presence of antibiotics (Blair et al. 2015). Further the antimicrobial resistance can be acquired through gaining antibiotic-resistant encoded genes from other bacteria through conjugation, transformation, and transduction. Conjugation is considered as most significant process of antibiotic resistance transmission in bacteria. The circular fragment plasmids of bacterial DNA facilitate this mechanism by independently replicating the chromosome and transfer DNA fragments through the formation of pilus when bacteria are close to each other. Transformation is also another way of transmission of antibiotic resistance through “naked” DNA from cell to cell. The free DNA originated from dead bacteria enters the receiving bacteria via cytoplasm. Genetic transfer through transduction occurs by means of a vector, mostly viruses “bacteriophages” that have the ability to infect bacteria. The virus having antibiotic-resistant coded bacterial gene transfer the genetic material to receiving bacteria. When an infecting bacteriophage transfer viral DNA to receiving bacteria, it will allow replication system of bacteria to continue to replicate infecting virus till bacterial cell expires (Alanis 2005).

In hospitals various factors are responsible for the greater resistance development in bacteria including patient’s survival in severe illness with the overuse of antibiotics, lack of effective precautionary measures, and lack of restrictions on the use of antibiotics and inappropriate prescription of antibiotics to patients. So these antibiotic-resistant bacteria and pathogens originated from the hospitals when enters into the environment can disseminate their resistance to the environmental bacteria and poses some serious consequences. This leads to severe infections resulting in the reduced effectiveness of antibiotics due to resistance genes transfer between pathogens, and more expensive and complex treatments for a longer period of time (Wellington et al. 2013). Bacteria have the ability to develop multidrug resistance through complex molecular mechanism which can increase the rate of mortality and morbidity through causing new types of infections.

2.6 Conclusion

Hospitals are serving as hotspot for the different types of antibiotics, resistance genes, and human pathogens. Antibiotics were extensively employed in the hospitals to treat various infections causing the spread of antibiotics and antibiotic-resistant bacteria from human intestine to the environment which has become a global threat. The data about the antibiotics consumption is needed to control the misuse of antibiotics and to design effective strategies. Treatment technologies needed to be installed to treat hospital waste prior to their discharge into the environment. Most importantly, antibiotic steward ship is needed to minimize the misuse and waste production in the hospital and to lower the clinical cost and improvement in the hospital treatments.