**4. Drug-resistant bacteria from HIV patients**

Human immunodeficiency virus (HIV)-infected individuals are highly vulnerable to a various opportunistic infections (OIs) due to their compromised immune system. For the prophylaxis of OIs, HIV patients are frequently exposed to high level of antimicrobial agents which leads to the emergence of multidrug-resistant bacteria. MDR bacteria become a major problem in the clinical management of HIV disease. Treatment of common bacterial infections like acute respiratory tract infections, urinary tract infections, wound infections, meningitis, and blood stream infections are very difficult when they are associated with MDR bacteria leading to increased morbidity and mortality. Multidrug resistant (MDR) pathogens are relentlessly multiplying in HIV patients and thus become an important circulating source of infection in the community. Globally, very few scientific data are available on the drug-resistant bacteria from HIV population.

Co-trimoxazole (also called as trimethoprim-sulfamethoxazole (TMP-SMX)) is a broad-spectrum antibiotic, used as a prophylactic agent against opportunistic infections among HIV/AIDS patients. Especially, TMP-SMX is an active drug against Pneumocystis pneumonia (PCP) caused by *Pneumocystis jirovecii* among HIV-infected patients [50, 51]. World Health Organization and Joined Nations Programme on HIV/AIDS have recommended TMP-SMX prophylaxis for immunosuppressed adults and children born to HIV-infected women [52–54]. Long-term receiving of TMP-SMX prophylaxis has lead to increase in the development of TMP-SMXresistant bacteria, which spreading in the bacterial community and cause therapeutic problems for bacterial infections in HIV population. In Enterobacteriaceae, sulfonamide drug resistance genes such as *sul1*, *sul2*, and *sul3* are responsible for dihydropteroate synthases, and more than 20 dihydrofolate reductase (*dfr*) genes conferring resistance to trimethoprim [55] (**Table 2**).

UTI accounts for consumption of large proportion of anti-bacterial drugs [18]. Resistance to commonly prescribed antibiotics for UTI is an expanding global problem both in developed as well as developing countries [56]. UTI became quite alarming as isolated uropathogens exhibit high percentage resistance to almost all antibiotics [57]. The pattern of antibacterial susceptibility of UTI causing pathogen has been changing over the years, and the drug resistant of the bacteria is influenced by the extensive and misuse of antibiotics and changing patient population, especially among immunocompromised patients. β-Lactam antibiotics such as penicillins, cephalosporins and carbapenems are the most commonly used antibacterial drugs. The predominant drug resistance mechanisms against β-lactam antibiotics among Gram-negative bacteria are the production of Extended Spectrum β-lactamases (ESBLs) and AmpC β-lactamases [58] and they are associated with increased morbidity and mortality with immunocompromised individuals. The frequency of *Pseudomonas aeruginosa* and *Staphylococcus aureus* as community-acquired pathogens is higher in HIV-infected individuals than in those not HIV infected. Methicillinresistant *Staphylococcus aureus* (MRSA) infection should be considered as a potential etiology for pneumonia, given that community outbreaks of MRSA have been seen in men who have sex with men and nasal carriage of MRSA is more common in HIV-infected individuals, particularly at lower CD4 cell counts. Multidrug resistance (MDR) bacteria like ESBL producers and MRSA are a major public health concern worldwide [21, 39] (**Table 2**).

emerge rapidly worldwide [47, 48]. β-Lactamase producing organisms pose a major problem for clinical therapeutics. The incidence of β- lactamase producing strains among clinical has been steadily increasing over the past few years resulting in limitation of therapeutic options. β-Lactamases are classified based on the molecules (Ambler Classification) and functions (Bush-Jacoby-Medeiros classification) of the enzymes [49]. Most important β-lactamase enzymes are extended spectrum β-lactamases (ESBLs), AmpC β- lactamase (AmpC) and

RTI: respiratory tract infections; BSI: blood stream infection; UTI: urinary tract infection; WI: wound infection; EI: enteric infection; OM: Otitis Media; amk – amikacin; amx – amoxicillin; amc - amoxicillin-clavulanic acid; amp – ampicillin; ctx – cefotaxime; fox – cefoxitin; cpd – cefpodoxime; caz – ceftazidime; cro – ceftriaxone; chl – chloramphenicol; cip – ciprofloxacin; dox – doxycycline; ery – erythromycin; gen – gentamicin; ipm – imipenemmem – meropenem; nit – nitrofurantoin; oxa – oxacillin; pen – penicillin; pip – piperacillin; tzp - piperacillin-tazobactam; tmp – trimethoprim;

**Isolated bacteria Drug resistance**

*E. coli*: amp-93.3%; sxt-90%; amc-43.3%; *K. pneumoniae*: amp-100%; sxt-72.7%; nit-33.3%;

MRSA-3%; VRE-1%; ESBL-62%; Multidrug resistant TB-22% Extensively drug-resistant TB-3.5%

*P. aeruginosa:* amp-73.3%; amc-53.3%; ery-40%

*E. coli*: amp & fox- 51.4%; ery-45.9% *K. oxytoca*: ery-62.5%; fox-50%; amp-43.8% *K. pneumoniae*: amp-51.2%; amc-48.6% *S. aureus*: amp-46.5%; fox-42.7%; ery-37.4%

*M. catarrhalis:* amk & amp-55.6% *P. mirabilis*: ery-100%; amc & amp- 66.7% *S. epidermidis:* ery-64.3%; fox-55.5%; amp-50%

*S. pneumoniae:* ery-71.4%; fox-42.9% *S. pyogenes:* amp-48.7%; ery-42.1%

amc-54.5%

*E. coli, 57.7% K. pneumoniae, 23.1% C. freundii, 3.9% S. aureus, 3.9% P. agglomerans, 1.9% S. agalactiae, 1.9%*

*P. aeruginosa, 24.1% E. coli, 16% A. baumannii, 15.1% K. pneumoniae, 13.4%*

*S. aureus, 4.4% S. pneumoniae, 1.8% Tuberculosis-19.3%*

*P. aeruginosa, 6.4% E. coli, 5.3% K. oxytoca, 5% K. pneumoniae, 12.4% S. aureus, 45.7% M. catarrhalis, 3.2% P. mirabilis, 1.1% S. epidermidis, 5.0% S. pneumoniae, 2.5%*

*Stenotrophomonas maltophilia, 11.6%*

Metallo β-lactamase (MBL).

sxt - trimethoprim-sulfamethoxazole.

**Table 2.** Bacterial infections and drug resistance in HIV patients.

**Infections, Reference/**

92 Advances in HIV and AIDS Control

**Country**

[43]

UTI (Tanzania)

RTI (China) [44]

OM (Tanzania)

[45]

WHO has documented that MDR-TB is emerging as a major challenge for tuberculosis control programs and is becoming extensively widespread today throughout the world, even in high-income countries with low TB incidence. Resistance to anti-TB drugs occurs due to misuse of drugs such as patients do not compete full course of treatment, wrong treatment provide by physicians, wrong dose or length of time for taking the drugs and supply of poor quality drugs. Multidrug-resistant TB is caused by *Mycobacterium tuberculosis* that is resistant to at least to two most potent TB drugs such as isoniazid and rifampicin. Extensively drugresistant TB (XDR-TB) is MTB resistant to isoniazid and rifampicin along with any fluoroquinolone and at least one of three injectable second-line drugs includes amikacin, kanamycin or capreomycin. Treatment options for XDR-TB have more side effects, and they are more expensive. XDR-TB can weaken the immune system, and persons are more likely to develop TB disease and they are at high risk of death.

In 2010, about 650,000 cases have MDR-TB, which account for 5% of all newly diagnosed TB patients, and more than 150,000 MDR-TB deaths are estimated to occur worldwide each year with case fatality rate of 30 per 100 individuals [59]. The proportion of MDR-TB reported globally ranges from 0 to 28.3% and 0 to 61.6% among new TB cases and among previously treated TB cases respectively [60]. People living with HIV are at a higher risk of developing MDR and XDR tuberculosis associated with increased mortality, and greatly reduced survival time of patients [61] (**Table 2**).

**7. Global action plan, WHO**

**Type of priority List of drug-resistant pathogens**

*Enterobacteriaceae*

*gonorrhoeae*

**Table 3.** Global priority of pathogens list by World Health Organization.

**interventions**

10–12%.

most evident for macrolides (65%).

WHO developed the global action plan with five strategic objectives to achieve the goal of ensuring continuity of successful treatment and prevention of infectious diseases with effective and safe medicines [64]. They (1) improve the awareness and understanding of antimicrobial resistance through effective communication, education and training, (2) strengthen the knowledge and evidence base through surveillance and research, (3) reduce the incidence of infection through effective sanitation, hygiene and infection prevention measures, (4) optimize the use of antimicrobial medicines in human and animal health and (5) develop the economic case for sustainable investment that takes account of the needs of all countries, and increase investment in new medicines, diagnostic tools, vaccines and other interventions.

Critical priority Carbapenem-resistant *Acinetobacter baumannii;* Carbapenem-resistant *Pseudomonas* 

Medium priority Penicillin-non-susceptible *Streptococcus pneumonia;* Ampicillin-resistant

High priority Vancomycin-resistant *Enterococcus faecium;* Methicillin-resistant, Vancomycinintermediate and resistant *Staphylococcus aureus*

*aeruginosa;* Carbapenem-resistant, 3rd generation cephalosporin-resistant

Drug-Resistant Bacterial Infections in HIV Patients http://dx.doi.org/10.5772/intechopen.78657 95

Clarithromycin -resistant *Helicobacter pylori;* Fluoroquinolone-resistant

3rd generation cephalosporin-resistant, fluoroquinolone-resistant *Neisseria* 

*Haemophilus influenza;* Fluoroquinolone-resistant *Shigella* spp.

*Campylobacter;* Fluoroquinolone-resistant *Salmonella* spp.

Examples of global research into antimicrobial resistance and its impact are given below [29]: • Chinese Ministry of Health in 2011, reduced unnecessary prescription of antimicrobials by

• The Swedish Strategic Programme against Antibiotic Resistance (STRAMA): decrease in antibiotic use for outpatients from 15.7 to 12.6 daily doses per 1000 inhabitants and from 536 to 410 prescriptions per 1000 inhabitants per year from 1995 to 2004. The decrease was

• WHO essential medicines policies: reductions in antibiotic use of ≥20% in upper respiratory tract infections and 30% of reduction in the use of antibiotics in acute diarrheal illness.

• Antimicrobial stewardship programme (2009–2014) in 47 South African hospitals: reduc-

**7.1. Examples for global impact of antimicrobial resistance research and** 

tion of antibiotic doses daily per 100 patient days from 101.4 to 83.04.

### **5. Future impact of antimicrobial resistance**

The two multidisciplinary research teams such as RAND Europe and KPMG, have provided their own high-level assessments of the future impact of antimicrobial resistance, based on scenarios for rising drug resistance and economic growth to 2050. The studies estimate 300 million people are expected to die prematurely due to drug resistance over the next 35 years and the world's Gross Domestic Product (GDP) will be 2% to 3.5% lower than it otherwise would be in 2050. This means that between now and 2050, the world can expect to lose between 60 and 100 trillion USD worth of economic output if antimicrobial drug resistance is not tackled. This is equivalent to the loss of around 1 year's total global output over the period, and will create significant and widespread human suffering. Furthermore, in the nearer term, they expect the world's GDP to be 0.5% smaller by 2020 and 1.4% smaller by 2030 with more than 100 million people having died prematurely [62].

## **6. Tackle of antimicrobial resistance**

WHO developed a global priority of pathogens list (global PPL) of antibiotic-resistant bacteria to help in prioritizing the research and development (R&D) of new and effective antibiotic treatments. Drug-resistant bacteria were categorized into critical priority, high priority and medium priority pathogens (**Table 3**) [63].


**Table 3.** Global priority of pathogens list by World Health Organization.
