Which medications in the drug class Antibiotics are used in the treatment of Pneumococcal Infections (Streptococcus pneumoniae)?

Updated: Jun 08, 2020
  • Author: Eduardo Sanchez, MD; Chief Editor: John L Brusch, MD, FACP  more...
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Penicillin and its derivatives are inexpensive effective antibiotics for treating pneumococcal infections when they are used against susceptible isolates. Penicillins can be administered orally or parenterally and work by inhibiting cell wall synthesis. Penicillin G is the parenteral drug of choice for susceptible S pneumoniae infections, and other parenteral beta-lactams do not provide additional or improved coverage (nor do beta-lactamase inhibitor combinations).

Cephalosporins' mechanism of action and modes of resistance are the same as for all other beta-lactams. First-generation cephalosporins provide similar coverage in the treatment of penicillin-susceptible strains, although many of them have higher MICs. Penicillin- and cefotaxime-susceptible strains of S pneumoniae were estimated at 96% and 97.9%, respectively. [98]

In most cases, macrolides have activity against penicillin-susceptible strains of S pneumoniae. However, between 1998 and 2011, resistance rates have increased to an estimated 25%-45% in the United States. [107]  In 2017, the CDC's active bacterial core surveillance report found the erythromycin resistance rate to be 29.3%. [98]

Macrolides have poor CSF penetration and should not be used to treatment meningitis. [108]

Most pneumococcal isolates in the United States remain susceptible to respiratory fluoroquinolones. In the United States, less than 1% of S pneumoniae isolates are resistant to levofloxacin, moxifloxacin, or gemifloxacin. [109] Ciprofloxacin and ofloxacin have limited activity against pneumococcal infections. Fluoroquinolones achieve excellent serum drug levels and tissue penetration. Specific populations in whom the use of fluoroquinolones is traditionally increased (eg, nursing home residents) have shown increased rates of pneumococcal resistance to fluoroquinolones, serving as a reminder that consideration of their empiric use in uncomplicated respiratory infections should be tempered by concern for the promotion of further antimicrobial resistance.

Vancomycin, dalbavancin, and telavancin are glycopeptide antibiotics that have demonstrated efficacy against pneumococcal infections. [110, 111] To date, no clinical or in vitro evidence of pneumococcal resistance to vancomycin has been reported in the United States, and it is the drug of choice (with a third-generation cephalosporin) in the treatment of penicillin-resistant pneumococcal meningitis.

The increasing number of pneumococcal isolates resistant to trimethoprim-sulfamethoxazole precludes its use unless susceptibilities are known and beta-lactam use is contraindicated.

Clindamycin may also be used to treat nonmeningeal S pneumoniae infections. Approximately 5%-10% of S pneumoniae strains in the United States are resistant to clindamycin. [26] As such, clindamycin should be used only after susceptibility testing has confirmed activity on clinical isolates. Penicillin or macrolide resistance may also be associated with clindamycin resistance in individual isolates.

Carbapenems are also effective against S pneumoniae but should be reserved for specific cases given their broad coverage and the potential for development of resistance by multiple organisms.

Cefotaxime (Claforan)

Third-generation cephalosporin with broad gram-negative spectrum, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms. Arrests bacterial cell wall synthesis by binding to one or more of the PBPs, in turn inhibiting bacterial growth. Safety profile is more favorable than aminoglycosides. DOC for meningitis (all ages), inpatient treatment of pneumonia, bacteremia, and other invasive infections.

Penicillin G (Pfizerpen)

DOC for severe infections, including meningitis attributed to susceptible strains of S pneumoniae. DOC for severe infections, excluding meningitis attributed to strains of S pneumoniae with intermediate susceptibility to penicillin.

Amoxicillin (Moxatag)

Has better absorption than penicillin VK and administration is q8h instead of q6h. For minor infections, some authorities advocate administration q12h. Probably most active of the penicillins for non–penicillin-susceptible S pneumoniae.


No advantage over penicillin G in the treatment of pneumococcal infections. Bactericidal activity against susceptible organisms. Alternative to amoxicillin when unable to take medication orally.


Alternative choice for parenteral treatment of pneumococcal infection outside CNS. Best beta-lactam for IM administration. Poor capacity to cross blood-brain barrier precludes use for treatment of meningitis.

Ceftriaxone (Rocephin)

May be used to treat pneumococci that have reduced susceptibility to penicillin. Generally not preferred for infections caused by high-level penicillin-resistance pneumococci. For empiric treatment of meningitis, use in conjunction with vancomycin or rifampin.

Azithromycin (Zithromax)

Generally better tolerated than erythromycin. Because of long half-life, treatment duration is reduced. Should not be used for meningitis owing to poor CSF penetration.


Always active against strains of S pneumoniae. DOC for the treatment of meningitis caused by non–penicillin-susceptible S pneumoniae. Has suboptimal capability to cross blood-brain barrier and should be administered with cefotaxime or ceftriaxone for the treatment of meningitis. In adults, glucocorticoids may decrease penetration of vancomycin in the CNS; avoid this medication unless specific indications exist. Vancomycin is frequently the preferred drug for the treatment of severe penicillin-resistant pneumococcal infections outside the CNS and for patients with an IgE-type allergy to penicillin. Only IV administration is effective.

The maintenance dose can be estimated using the following formula: 150 + 15 times the creatinine clearance in mL/min = mg of vancomycin to be administered daily.

Clindamycin (Cleocin)

Lincosamide for treatment of serious skin and soft-tissue staphylococcal infections. Also effective against aerobic and anaerobic streptococci (except enterococci). Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Meropenem (Merrem IV)

A carbapenem antibiotic alternative for patients allergic to penicillin with meningitis or other severe invasive infections (good CSF penetration). Has been used successfully in patients with meningitis caused by penicillin-resistant pneumococci.

Linezolid (Zyvox)

Prevents formation of functional 70S initiation complex, which is essential for bacterial translation process. Bacteriostatic against enterococci and staphylococci and bactericidal against most strains of streptococci. Used as alternative in patients allergic to vancomycin and for treatment of vancomycin-resistant enterococci.

Ceftaroline (Teflaro)

Appears to be effective in vitro against pneumococcal isolates. A study in US medical centers from 2009 through 2012 that evaluated multidrug-resistant S pneumoniae (not susceptible to penicillin, ceftriaxone, erythromycin, tetracycline, trimethoprim-sulfamethoxazole, and levofloxacin) showed that ceftaroline was 16 times more potent than ceftriaxone. [93]

Tigecycline (Tygacil)

A glycylcycline antibiotic that is structurally similar to tetracycline antibiotics. Inhibits bacterial protein translation by binding to 30S ribosomal subunit and blocks entry of amino-acyl tRNA molecules in ribosome A site. Indicated for complicated skin and skin structure infections caused by E coli, E faecalis (vancomycin-susceptible isolates only), S aureus (methicillin-susceptible and methicillin-resistant isolates), S agalactiae, S anginosus group (includes S anginosus, S intermedius, and S constellatus), S pyogenes, and B fragilis.

Trimethoprim/sulfamethoxazole (Bactrim, Bactrim DS, Sulfatrim Pediatric)

Sulfamethoxazole and trimethoprim is a sulfonamide derivative antibiotic. This agent inhibits bacterial synthesis of dihydrofolic acid by competing with paraaminobenzoic acid, thereby inhibiting folic acid synthesis and resulting in inhibition of bacterial growth.

Levofloxacin (Levaquin)

Levofloxacin is rapidly becoming a popular choice in pneumonia; this agent is a fluoroquinolone used to treat CAP caused by S aureus, S pneumoniae (including penicillin-resistant strains), H influenzae, H parainfluenzae, Klebsiella pneumoniae, M catarrhalis, C pneumoniae, Legionella pneumophila, or M pneumoniae.

Levofloxacin is the L stereoisomer of the D/L parent compound ofloxacin, the D form being inactive. It has good monotherapy with extended coverage against Pseudomonas species and excellent activity against pneumococcus. Levofloxacin acts by inhibition of DNA gyrase activity. The oral form has a bioavailability that is reportedly 99%.

The 750-mg dose is as well tolerated as the 500-mg dose, and it is more effective. Other fluoroquinolones with activity against S pneumoniae may be useful and include moxifloxacin, gatifloxacin, and gemifloxacin.

Moxifloxacin (Avelox, Moxifloxacin Systemic)

Moxifloxacin is a fluoroquinolone that inhibits the A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription. Use caution in prolonged therapy, and perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic). Note that superinfections may occur with prolonged or repeated antibiotic therapy, and fluoroquinolones have induced seizures in patients with CNS disorders and caused tendinitis or tendon rupture.

Gemifloxacin (Factive)

Gemifloxacin is a fluoroquinolone that inhibits the A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication, DNA repair, recombination, transposition, and transcription.

Clarithromycin (Biaxin, Biaxin XL)

Clarithromycin is another initial drug of choice that is used in otherwise uncomplicated pneumonia. It is used to treat CAP caused by H influenzae, M pneumoniae, S pneumoniae, M catarrhalis, H parainfluenzae, or C pneumoniae (TWAR strain). Clarithromycin appears to cause more GI symptoms (eg, gastric upset, metallic taste) than azithromycin.

This agent is a semisynthetic macrolide antibiotic that reversibly binds to the P site of the 50S ribosomal subunit of susceptible organisms and may inhibit RNA-dependent protein synthesis by stimulating dissociation of peptidyl t-RNA from ribosomes, causing bacterial growth inhibition.

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