Salmonella typhi and S. paratyphi A
Enteric fever continues to be a major public health problem in our country. Chloramphenicol remained the drug of choice for the treatment of this infection till plasmid mediated chloramphenicol resistance was encountered 27-29.
Following this ciprofloxacin became the mainstay of treatment. Being a safer and more effective drug it was used even when the bacteria was sensitive to chloramphenicol30. The isolates of S. typhi and S. paratyphi A showed higher MIC to ciprofloxacin31 and there is clinical resistance to treatment with ciprofloxacin in the patients suffering from enteric fever32,,33. The choice left now is an expensive drug like ceftriaxone or cefexime.
Infections with S. paratyphi A, which were always considered to be mild have also shown similar trends and the complications occur if the treatment is delayed33. Shigella sp.
The emergence of multi drug resistant Shigella has remained a cause of concern in endemic regions34. The nalidixic acid resistance has increased for Shigella sonnei in some of the Indian isolates. This is noteworthy, since it has been recommended for the empirical treatment of patients suspected to have shigellosis35. Multi drug resistant Shigella dysenteriae serotype 1 strains have re-emerged in patients hospitalized with diarrhoea which were multi drug resistant (resistant to norfloxacin and ciprofloxacin)36.
Resistance in V. cholerae is being encountered in most of the endemic areas37,38. Overall 90 per cent of V. cholerae isolates show resistance to at least one of the commonly used antibiotics to treat gastrointestinal infections39. The resistance to nalidixic acid being the highest followed by furazolidine, co-trimoxazole and tetracycline. Though the role of antibiotics is limited in the management of cholera, they still play an important role in the management of critically ill patients who need hospitalization.
Methicillin resistant Staplylococcus aureus (MRSA) MRSA is an important cause of nosocomial infections worldwide. These are also resistant to most of the other antibiotics and in many cases the only choice left is vancomycin40,41. There is evidence to show that MRSA is not only limited to hospital environment but can cause infections in community, a fact which is alarming42. This could be due to the carriers in the hospitals being discharged or health care workers carrying it with them. Similarly methicillin resistant coagulase negative staphylococci (CoNS) are also increasing in numbers in such environment, and the multi drug resistant strains are higher amongst CoNS40. As yet no vancomycin or teichoplanin resistance has been reported from India. But continuous monitoring is required as presence of VISA strains has been reported causing infections in some parts of the world43.
The enterococci are inherently resistant to many antibiotics but the combination of penicillin and gentamicin being synergistic remained the treatment of choice for infections related to this bacteria44. Now the strains have emerged which do not respond to treatment with this combination as they have a high level of resistance of aminoglycosides and are called as HLAR45,46. Vancomycin is the only alternative left for the treatment of infections caused by HLAR strains. But a major problem is that vancomycin use is a risk factor for colonization and infection with VRE. Vancomycin resistance, emerging amidst the increasing incidence of high level resistance to penicillins and aminoglycosides, has limited treatment options for bacteraemia due to E.faecalis or E.faecium in the hospitals, which is increasingly being encountered. Though at present there is limited number of reports of VRE from India46, it needs continuous monitoring. All these strains are presently sensitive to linezolid.
Emergence of VRE may also increase the possibility of the emergence of vancomycin resistant S.aureus. Conjugative transfer of high level vancomycin resistance from E. faecalis to S. aureus in the laboratory has been possible and there is a possibility that this resistance may be transferred to wild type S. aureus13.
S.pyogenes, the group A streptococcus has remained sensitive to penicillin till now but it continues to cause invasive infections and toxic shock syndrome47,48. Indian isolates have remained sensitive to penicillin but the resistance to macrolide is being encountered47. The penicillin susceptibility of this organism now needs continuous monitoring.
There is a concern of spread of penicillin resistant S.pneumoniae strain throughout the world49. Though the prevalence of this resistance is at present not a major problem in our country, intermediate resistance to penicillin has been reported50. Resistance to cotrimoxazole and chloramphenicol is seen more frequently. The isolates showing total resistance to penicillin have been reported from India, which were also multi drug resistant being resistant to cefotaxime, erythromycin, chloramphenicol and trimethoprimsulphamethoxazole51.
In India, b-lactamase mediated resistance in H.influenzae is increasingly being encountered52. Recently a multicentric study showed an increasing resistance to ampicillin, chloramphenicol, erythromycin and trimethoprim-sulphamethoxazole in H. influenzae strains isolated from different parts of India53. All the strains however were sensitive to cefotaxime.
Gram negative bacilli
The most important cause of hospital acquired infections are the Gram negative bacteria. These bacteria have acquired resistance to multiple antibiotics. Not only in the hospital settings but also in the community acquired infections the Gram negative bacteria pose therapeutic problem. E. coli is an important cause of community acquired urinary tract infections but resistance is seen in nearly 70-80 per cent of the strains to the commonly used antibiotics54. In patients suffering from cystic fibrosis colonization with Psuedomonas aeruginosa in the community set up is very common. These patients can harbour multi drug resistant strains over a period of time as they are on long term antibiotic prophylaxis and need frequent antibiotic treatment55. Among the nosocomial pathogens multi drug resistant Gram negative bacteria are the important cause of hospital associated infections56-61. These bacteria can survive for a long period of time in adverse environment and once having entered the host, can lead to long term colonization. Nosocomial infections due to ESBL producing Klebsiella pneumoniae, P. aeruginosa, Acinetobacter baumanii, Serratia marsecens, E. coli etc., are the main threat in the present scenario60,62,63. The therapeutic options are limited in infections caused by these agents.