Penicillins Streptococcus pneumoniae

In contrast to macrolides, the targets of (3-lactams, the penicillin binding proteins (PBPs) require several mutations in order to become resistant while simultaneously maintaining their viable function as cell wall transpeptidases/transglycosidases. Thus, in order to achieve clinically relevant resistance Streptococcus pneumoniae uses a unique strategy to rapidly accumulate several point mutations. Due to its natural competence for transformation during respiratory tract... 

Streptococcus pneumoniae remains the commonest cause of pneumonia and responds well to penicillin. In addition, a number of atypical infections may cause pneumonia and include Mycoplasma pneumoniae, Legionella pneumophila, psittacosis and occasionally Q fever. With psittacosis there may be a history of contact with parrots or budgerigars while Legionnaires disease has often been acquired during hotel holidays... 

Streptococcus pneumoniae Penicillin susceptible Penicillin intermediate Penicillin resistant Group B Streptococcus Staphylococcus aureus Methicillin susceptible Methicillin resistant Staphylococcus epidermidis Listeria monocytogenes... 

Higher dose amoxicillin, amoxicillin-davulanate (eg., 90 mg/kg/day) is used for penicillin-resistant Streptococcus pneumoniae fluoroquinolones are avoided in pediatric patients because of the potential for cartilage damage however, their use in pediatrics is emerging. Doses shown are extrapolated from adults and will require further study. 

Treatment failure or prior antibiotic therapy in past 4-6 weeks High suspicion of penicillin-resistant Streptococcus pneumoniae... 

The emergence of multidrug-resistant Gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP), and vancomycin-resistant enterococci... 

Kobayashi R, Konomi M, Hasegawa K, Morozumi M, Sunakawa K, Ubukata K. (2005) In vitro activity of tebipenem, a new oral carbapenem antibiotic, against penicillin-nonsusceptible Streptococcus Pneumoniae. Antimicrob Agents Chemother 49 889-894. 

Community-acquired pneumonia Caused by Streptococcus pneumoniae (penicillin-susceptible strains only), including cases with concurrent bacteremia, Haemophiius infiuenzae (beta-lactamase-negative strains only), or Moraxeiia catarrhaiis. 

Levofloxacin (1), the levo-isomer or the (5)-enantiomer of ofloxacin, received FDA approval in 1996 (Fish, 2003 Hurst et al., 2002 Mascaretti, 2003 Norrby, 1999 North et al., 1998). The initial approval covered community-acquired pneumonia, acute bacterial exacerbation of chronic bronchitis, acute maxillary sinusitis, uncomplicated skin and skin structure infections, acute pyelonephritis, and complicated urinary tract infections (North et al., 1998). Four years later, the levofloxacin indication list grew to include community-acquired pneumonia caused by penicillin-resistant Streptococcus pneumoniae. In addition, in 2002, nosocomial (hospital-acquired) pneumonia caused by methicillin-susceptible Staphylococcus aureus, Pseudomonas aeruginosa, Serratia marcescens, Haemophilus influenzae, Kliebsella pneumoniae, and Escherichia coli was added (Hurst et al., 2002). Finally in 2004, LVX was approved as a post-exposure treatment for individuals exposed to Bacillus anthracis, the microbe that causes anthrax, via inhalation (FDA, 2004). 

Worldwide Streptococcus pneumoniae % susceptibility to penicillin is decreasing. In some countries up to two-thirds of the clinical isolates have reduced susceptibility to penicillin or are highly resistant to this drug. Moreover, the rate of resistance to other drugs commonly used for RTI including erythromycin, tetracycline and trimethoprim-sulfamethoxazole is higher in penicillin-resistant than penicillin-susceptible strains. Monitoring local or hospital resistance patterns of pneumococci is, therefore, needed. 

Staphylococcus aures (penicillin-sensitive) Staphyloccocus aureus (penicillin-resistant) Streptococcus pyogenes Streptococcus pneumoniae Enterococcus faecalis ... 

Guenzi, E. Case, A.M. Sicard, M.A. Hakenbeck, R. A two-component signal-transducing system is involved in competence and penicillin susceptibility in laboratory mutants of Streptococcus pneumoniae. Mol. Microbiol., 12, 505-515 (1994)... 

Streptococcus pneumoniae Arthritis otitis pneumonia sinusitis If penicillin sensitive ampicillin or penicillin G or V If penicillin resistant vancomycin rifampin A cephalosporin erythromycin azithromycin clarithromycin imipenem meropenem a fluoroquinolone trimethoprim-sulfamethoxazole... 

Streptococcus pneumoniae, penicillin-susceptible (MIC d2) Penicillin6 Doxycycline, ceftriaxone, cefuroxime, erythromycin, imipenem, meropenem, linezolid... 

M Jamin, C Damblon, S Millier, R Hakenbeck, JM Frere. Penicillin-binding protein 2x of Streptococcus pneumoniae, enzymic activities and interactions with [3-1 ac-tams. Biochem J 292 735-741, 1993. 

G Zhao, TI Meier, J Hoskins, SR Jaskunas. Penicillin-binding protein 2a of Streptococcus pneumoniae, expression in Escherichia coli and purification and refolding of inclusion bodies into a soluble and enzymatically active enzyme. Prot Expr Purif 16 331-339, 1999. 

G Zhao, WK Yeh, RH Carnahan, J Flowkowitsch, TI Meier, WE Alborn, GW Becker, SR Jaskunas. Biochemical characterization of penicillin-resistant and -sensitive penicillin-binding protein 2x transpeptidase activities of Streptococcus pneumoniae and mechanistic implications in bacterial resistance to [3-lactam antibiotics. J Bacteriol 179 4901-4908, 1997. 

S Pares, N Mouz, Y Petillot, R Hakenbeck, O Dideberg. X-ray structure of Streptococcus pneumoniae PBP2x, a primary penicillin target enzyme. Nat Struct Biol 3 284-289, 1996. 

CG Dowson, A Hutchison, JA Brannigan, RC George, D Hansman, J Linares, A Tomasz, J Maynard-Smith, BG Spratt. Horizontal transfer of penicillin-binding protein genes in penicillin-resistant clinical isolates of Streptococcus pneumoniae. Proc Natl Acad Sci (USA) 86 8842-8846, 1989. 

CG Dowson, A Hutchison, BG Spratt. Extensive remodeling of the transpeptidase domain of penicillin-binding protein 2B of a penicillin-resistant South African isolate of Streptococcus pneumoniae. Mol Microbiol 3 95-102, 1989. 

J Hoskins, P Matsushima, DL Mullen, J Tang, G Zhao, TI Meier, T Nicas, SR Jaskunas. Gene disruption studies of penicillin-binding proteins la, lb, and 2a in Streptococcus pneumoniae. J Bacteriol 181 6552-6555, 1999. 

G Laible, R Hakenbeck, MA Sicard, B Joris, JM Ghuysen. Nucleotide sequences of the pbpX genes encoding the penicillin-binding proteins 2x from Streptococcus pneumoniae R6 and a cefotaxime-resistant mutant, C506. Mol Microbiol 3 1337-1348, 1989. 

A Severin, AM Figueiredo, A Tomasz. Separation of abnormal cell wall composition from penicillin-resistance through genetic transformation of Streptococcus pneumoniae. J Bacteriol 178 1788-1792, 1996. 

---