KEYWORDS: 

INTRODUCTION
Antimicrobial prophylaxis (AP), a strategy commonly employed to prevent infections, including surgical site infections, can be categorized as primary (preventing initial infection) or secondary (preventing recurrence or reactivation of latent infection). The indications for AP can be broadly grouped into medical prophylaxis, prophylaxis for non-surgical interventions (e.g., for endoscopic procedures) and surgical prophylaxis. A recent Indian survey revealed that 42.8% of antimicrobial prescriptions were for prophylactic purposes1. While extensive literature focuses surgical or perioperative AP, information regarding medical AP is comparatively scarce and often overlooked. However, medical AP can be grouped into three main categories.

a.  Post-exposure prophylaxis (PEP)

b. Pre-exposure prophylaxis (PrEP)

c.  Secondary prophylaxis in recurrent/latent conditions

Medical prophylaxis is crucial in India’s diverse healthcare setting to reduce disease morbidity and mortality, particularly given varied population, health literacy levels, and access issues. Appropriate prophylactic therapy can prevent disease transmission, minimize disease complications, and mitigate the spread of antimicrobial resistance (AMR).  This intervention can even be considered as a ‘low-hanging fruit’ of antimicrobial stewardship practices. Despite clear national guidelines, the uptake of prophylactic regimens remains inconsistent in India.  For example, adherence to national guidelines in India, such as those promoting isoniazid preventive therapies under Revised National Tuberculosis Control Programme, is often poor2, 3. Despite existing individual recommendations of AP in medical settings, compliance is often low.

This narrative review offers concise guidance to healthcare workers (HCWs) and the public on medical AP for common conditions, detailing specific indications, recommended antimicrobial agents, doses, frequency and duration. All dosing recommendations assume normal renal and hepatic function, and the absence of contraindications. Prior to initiating AP, it is essential to discuss the potential risks and benefits of the proposed regimen with the healthy individual or patient.

Search Methodology

A narrative review approach was adopted. Relevant literature was identified through searches of PubMed, Google Scholar, and official guidelines from national (ICMR, MOHFW, NACO, NTEP) and international (WHO, CDC) bodies. Priority was given to Indian guidelines and high-quality systematic reviews/meta-analyses. The review emphasizes commonly recommended AP regimens applicable to Indian settings.

A. POST- EXPOSURE PROPHYLAXIS

Post-exposure prophylaxis (PEP) plays a crucial role in preventing infections following a recognized or potential exposure to infectious agents. PEP is particularly important for infections associated with high infectivity, severe morbidity, or mortality, and in settings where immediate containment is critical to public health.

1. Antimicrobial Prophylaxis for Bite wounds

Prophylactic antibiotic use following bite wounds aims to prevent infections (relative risk =0.56, NNT =14), particularly in high-risk individuals, although evidence for universal use is limited4. Prophylaxis is recommended for immunocompromised patients, asplenic individuals, those with advanced liver disease, edema at the wound site, moderate to severe injuries (particularly to the hand, face, or near joints), or delayed presentation5.

2. Antimicrobial Prophylaxis for Influenza/Flu

Antiviral prophylaxis for influenza is indicated in certain high-risk individuals within 48 hours of exposure to an infectious person. This includes close contact (within approximately 6 feet for >15minutes) during the infectious period (1 day before to 5 days after symptom onset in the index case) (Table 1). It reduces the likelihood of symptomatic influenza, thereby lowering hospitalization rates6. 

Table 1: At risk individuals for influenza (Flu) prophylaxis upon exposure (Adapted from CDC)

3.  Doxy PEP for sexual transmitted infections

Giving the rising rates of syphilis, chlamydia, and gonorrhea, particularly among men who have sex with men and transgender women, doxycycline post-exposure prophylaxis (doxy PEP) has emerged as an effective strategy. Doxycycline taken within 72 hours after sex reduces syphilis and chlamydia infections by >70% and gonorrhea by ~50%7.

4.  HIV PEP

HIV PEP is crucial to prevent infection following exposure to blood or potentially infectious materials. NACO recommends PEP for exposures involving mucous membrane or compromised skin exposure with a large volume of infectious material, percutaneous injuries (e.g., superficial scratches, deep injuries with hollow-bore needles) involving infected material, irrespective of the source’s viral load or CD4 count. It is also recommended in cases of small-volume exposure if the source patient has advanced HIV disease with a high viral load. It should ideally be started within 2 hours of exposure and can be considered up to 72 hours8.

5.  AP for pertussis and diphtheria

Pertussis remains endemic in parts of India, and its high infectivity justifies the use of AP among close contacts. Early initiation within 21 days of exposure is recommended to prevent clinical disease, particularly in vulnerable neonates and infants9. For diphtheria, the WHO recommends erythromycin for exposed individuals, along with active immunization with the diphtheria vaccine10.

6.  PEP for zoonotic diseases

During the peak transmission season of leptospirosis, doxycycline may be given to agricultural workers (e.g., paddy field workers), canal cleaning workers in endemic areas where clustering of cases has been reported11. For high-risk laboratory Brucella exposures (including direct personal exposure such as sniffing cultures, direct skin contact; working with cultures outside biosafety level 3 containment; or presence during aerosol-generating procedures involving the isolates), PEP with doxycycline and rifampicin for three weeks is recommended12.

7.  PEP for Hansen disease (or leprosy)

Similarly, AP is recommended by WHO for close contacts of Hansen disease (defined as having been in contact for 20 hours or more per week for over 3 months during the past year) as it reduces the risk of developing leprosy in contacts by 60%13.

8.  Others

Close contacts of persons with meningococcal disease warrants AP, irrespective of vaccination status. Close contacts include household members, day care centre staff, and any person directly exposed to an infected person’s oral secretions in the 7 days before symptom onset. AP is recommended as soon as possible and no more than 48 hours after exposure14.

Rifampicin is recommended for chemoprophylaxis in invasive Haemophilus influenzae type b disease as it achieves high concentrations in respiratory secretions. Prophylaxis is indicated for all household members with unvaccinated children aged less than 4 years or immunocompromised individuals aged less than18 years. It is not indicated for non-type b H. influenzae exposures15.

РЕP against anthrax should be offered to all individuals who have documented or suspected exposure to aerosolized B. anthracis to prevent inhalational anthrax16. ΡЕР should start as soon as possible following exposure and ideally within 48 hours. For unprotected face-to-face contact with pneumonic plague patients, PEP is given orally for seven days17.

B. PRE EXPOSURE / TRAVEL PROPHYLAXIS

Traveler’s diarrhoea remains common globally despite improvements in sanitation and hygiene, leading to disruptions and health risks. Routine AP is not recommended but may be considered in high-risk travellers (e.g., individuals with immunosuppression, inflammatory bowel disease or severe kidney disease). It helps prevent diarrhoea in roughly 58 to 88% of travelers18.

In India, where Plasmodium falciparum malaria is predominantly chloroquine-resistant, current CDC and WHO guidelines recommend AP for travellers to those areas. Pregnant travellers should ideally avoid chloroquine-resistant malaria-endemic regions; if travel is unavoidable, mefloquine is the preferred chemoprophylaxis in chloroquine-resistant zones (doxycycline is contraindicated, and atovaquone-proguanil is not recommended during pregnancy) 19.

PrEP for HIV is highly effective when used correctly and consistently. It reduces the risk of HIV infection by over 90% from sexual exposure and around 70% from intravenous drug use. Sexually active, HIV- negative individuals who are at substantial risk and free of contraindications or acute HIV symptoms are eligible for PrEP20.

C. SECONDARY PROPHYLAXIS IN RECURRENT/LATENT CONDITIONS  

1. Antimicrobial prophylaxis in immunocompromised individuals

AP is recommended for patients at high risk for febrile neutropenia, including those expected to have profound, protracted neutropenia (< 100 neutrophils/cm3 for > 7 days), such as patients with acute myeloid leukemia/myelodysplastic syndromes or those undergoing HSCT treated with myeloablative conditioning regimens. A Fluoroquinolone (number needed to treat to prevent 1 death is 29) and triazole or echinocandin are recommended during period of expected neutropenia. HSV-seropositive patients undergoing allogeneic stem-cell transplantation or leukaemia induction should receive nucleoside analogs like acyclovir21. Brief overview of AP for patients undergoing solid organ transplantation is presented in table 2.

Table 2: Summary of all antimicrobial prophylaxis to be used in Indian medical setting.

Patients receiving a glucocorticoid dose equivalent to ≥ 20 mg of prednisone daily (e.g., 3 mg dexamethasone) for one month or longer, along with another cause of immunosuppression (such as a hematologic malignancy or use of additional immunosuppressive agents like rituximab or checkpoint inhibitors), are considered high risk for Pneumocystis pneumonia (PCP) 22. 

1. Antimicrobial prophylaxis in people living with HIV

People living with HIV (PLHIV) are susceptible to a multitude of opportunistic infections. Under the NACO guidelines, AP includes cotrimoxazole for PCP, isoniazid for tuberculosis (TB), and fluconazole for cryptococcal meningitis(8). Cotrimoxazole is indicated for adults and adolescents with CD4 counts <350 cells/mm³ or those in WHO clinical stages 3 and 4 in PLHIV who completed treatment for PCP. It also provides protection against toxoplasmosis, bacterial pneumonias, nocardiosis, and isosporiasis8.

Fluconazole is used for cryptococcal infection after successful completion of the maintenance phase, for at least 1 year or until CD4 count ≥ 100 cells/mm3 and HIV plasma viral load < 1000 copies/ml8. If there is a delay in initiating ART with CD4 <50 cells/mm3, azithromycin can be given for Mycobacterium avium complex prophylaxis.

2. Antimicrobial prophylaxis to prevent active tuberculosis

Tuberculosis preventive therapy (TPT) aims to prevent progression from latent TB infection to active disease, particularly in high-risk groups. TPT is recommended as it reduces the risk of TB disease by 60%(23). In household contacts of TB over 5 years and other high-risk groups such as those on immunosuppressive therapy, silicosis, anti-TNF treatment, dialysis, or transplantation, TPT is recommended only for those who test positive on TST/IGRA. In people living with HIV and household contacts under 5 years of TB patients, isoniazid for 6 months is recommended irrespective of TST/IGRA results23. Isoniazid preventive therapy is not recommended if there is active TB, hepatitis, peripheral neuropathy, known MDR-TB exposure, or hepatotoxic drug use.

Preventive treatment for household contacts of bacteriologically confirmed pulmonary tuberculosis patients varies by the index patient’s drug susceptibility. Six months of levofloxacin is advised when the index patient has multidrug-resistant tuberculosis (MDR-TB) that is sensitive to fluoroquinolones. For contacts of patients with isoniazid-resistant, rifampicin-sensitive tuberculosis, four months of rifampicin is recommended.

3. Antimicrobial prophylaxis to prevent recurrent urinary tract infections

Recurrent urinary tract infection (rUTI), defined as two or more infections in six months or three or more in one year, is a common condition with a high economic burden affecting women globally. Around 20–40% of women with a prior UTI experience recurrence, 25–50% of whom have multiple episodes24. Daily AP (e.g., TMP-SMX, nitrofurantoin) for 6–12 months is effective. Post-coital prophylaxis, as a form of PEP, is beneficial for sexually related rUTIs with fewer adverse effects. Long-term prophylaxis beyond one year lacks strong evidence.

4. Antimicrobial prophylaxis in respiratory diseases

Acute exacerbations of chronic obstructive pulmonary disease are associated with increased hospitalization rates and mortality. Given that acute exacerbations are often triggered by heightened airway inflammation and bacterial infections, macrolides, due to their anti-inflammatory and antimicrobial properties, have emerged as a potential preventive strategy. Macrolides decrease the proportion of patients who develop exacerbations from 68% to 57%25. Bronchiectasis exacerbations are associated with progressive lung damage and mortality. AP is indicated for adults with bronchiectasis who experience ≥ 3 exacerbations per year. Azithromycin reduced exacerbations to 0.59 per patient, compared to 1.57 per patients for placebo during 6 months in the EMBRACE trial26. Inhaled antibiotics (gentamicin/colistin) are preferred for P.aeruginosa infection, with macrolides as alternatives or adjuncts. For adults with bronchiectasis not infected with P.aeruginosa infection macrolides are recommended, with other oral or inhaled antibiotics as later options27.

5. Antimicrobial prophylaxis in chronic liver disease

Spontaneous bacterial peritonitis (SBP) prophylaxis aims to prevent both recurrence (68% with placebo vs 20% with norfloxacin) and first episode (60% vs 7%) due to the high risk of morbidity and mortality associated with SBP in cirrhotic patients(28). Secondary prophylaxis is indicated for patients recovering from a prior SBP episode, with oral norfloxacin being the preferred agent. In primary prophylaxis, antibiotics are reserved for certain high-risk patients. For those with cirrhosis and acute upper gastrointestinal bleeding, IV ceftriaxone is preferred. In patients with low ascitic fluid protein (<1.5 g/dL) combined with either renal dysfunction or advanced liver failure, norfloxacin is recommended as long as high risk factors are present28. Alternative options like rifaximin or sulfamethoxazole/trimethoprim have been explored, though evidence remains limited.

Hepatic encephalopathy (HE) is a frequent and debilitating complication of liver disease, profoundly impacting patients and caregivers. Lactulose is widely used to prevent recurrence of overt HE (OHE). Rifaximin can be an adjunct to lactulose for secondary prophylaxis following ≥1 additional episodes of OHE within 6 months of the first episode29.

6. Antimicrobial prophylaxis in cardiac diseases

In rheumatic heart disease, long-term penicillin prophylaxis is essential to prevent recurrence of rheumatic fever. Depending on the presence and severity of carditis, the duration may extend to 10 years or lifelong30.

AP is recommended only for patients at the highest risk of complications from viridans group Streptococcal infective endocarditis before dental procedure involving manipulation of gingival tissues, the periapical region of teeth, or perforation of the oral mucosa. Maintenance of good dental hygiene and regular dental care are more important than AP for preventing infective endocarditis (Table 3)31.

Table 3: High risk cardiac lesions for which endocarditis prophylaxis is suggested before dental procedures.

1. Antimicrobial prophylaxis to prevent recurrent cellulitis

Despite successful management, cellulitis – a bacterial infection of the skin and subcutaneous tissue – recurs frequently. Major risk factors for recurrence include a prior episode of cellulitis, chronic edema, dermatomycosis, venous insufficiency, obesity, diabetes, and peripheral vascular disease. AP can be considered when there are ≥ 2 episodes of cellulitis in the last one year. AP decrease recurrence by 69% (number needed to treat =6)32, 33.

2. Antimicrobial prophylaxis in hypo splenic/asplenic individuals

Individuals with absent or dysfunctional spleen are at increased risk of severe infections, particularly from encapsulated organism including Streptococcus pneumoniae, Haemophilus influenzae type b and Neisseria meningitidis. Lifelong AP should be considered in individuals with high-risk factors for invasive pneumococcal disease (age <16 or >50 years, inadequate serological response to pneumococcal vaccination, previous invasive pneumococcal disease, sepsis, ongoing immunosuppression) 34. Penicillin prophylaxis is recommended as it reduces pneumococcal infections (90 vs 33 per 1000 person-years) 35 in children under 5 with sickle cell disease, while the PROPS II trial found no significant increase in risk upon withdrawal of prophylaxis after 5 years36. 

 DISCUSSION

This narrative review highlights the current recommendations and practices related to medical AP in India. Evidence-based guidelines, including those from the Indian ICMR, the WHO, and specialty societies, provide clear directives on indications, agent selection, dosage, and duration of prophylaxis in various medical conditions. However, translating these guidelines into routine practice remains a significant challenge. Variations in clinician awareness, access to appropriate antimicrobial agents, and monitoring systems often result in either underuse or inappropriate prolonged use of prophylaxis. Both scenarios contribute to adverse outcomes, including preventable infections or, conversely, AMR.

In the Indian healthcare landscape, where infectious diseases such as immunocompromised conditions, chronic organ diseases, tuberculosis, HIV, and rheumatic fever remain endemic, the judicious use of medical prophylaxis is particularly crucial. The emergence of MDRs further reinforces the need for stringent adherence to prophylaxis protocols. Local data on resistance patterns, however, remain limited for certain prophylactic indications, and there is often reliance on international evidence that may not entirely reflect the Indian scenario.

Additionally, there is a need to strengthen antimicrobial stewardship initiatives that encompass not just therapeutic but also prophylactic use. Educational interventions for healthcare providers, development of institutional protocols, and regular audits could enhance compliance and ensure that prophylaxis contributes positively to public health outcomes without exacerbating AMR.

CONCLUSIONS

Medical AP is a cornerstone of preventive medicine, especially crucial in India’s diverse, high- burden healthcare setting. For HCWs, understanding indications and adhering to evidence-based protocols for appropriate regimens are critical. Table 2 summaries common conditions with indications of AP and drug regimens. Patient awareness and compliance are key to preventing complications and improving long-term outcomes. Effectively integrating these strategies into routine practice across India will significantly bolster public health, reduce disease impact, and crucially help curb the escalating threat of AMR. To optimize its benefits and mitigate risks, a coordinated integral approach involving guideline dissemination, surveillance, research, and stewardship is essential.

CONFLICTS OF INTEREST STATEMENT

The authors declare no conflict of interest.

SOURCE OF FUNDING

None

AUTHOR’S CONTRIBUTION

PKP, VT: Conceptualization; Data collection; Analysis; Writing the draft; critically review; Approve

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